Lecture 1 2011 9-10-11 Post
Transcript of Lecture 1 2011 9-10-11 Post
Introduction to BiochemistryBIOS E‐10
Saturday 9‐10‐11
Robin Haynes
BIOS E‐10 Business
1‐ Course details2‐ Our AWESOME team of Teaching Assistants3‐ Review ldquoundergraduate sectionsrdquo4‐ Graduate sections5‐ Office hours6‐ Exams and problem sets7‐ Course policies (detailed in syllabus)8‐ Saturday classes ndash THE GOOD9‐ Saturday classes ndash THE BAD10‐ The obvious
1‐ Course Details
Suggested textbook Essential Biochemistry Pratt and Cornely‐‐Wiley Plus option‐‐
Alternative Lehninger Principles of Biochemistry (5th edition) Nelson and Cox
Head TA Laura Magnotti
Course email address biocheme10gmailcom
Course website httpisitesharvardeduicbicbdokeyword=k81329amppageid=icbpage434280
2‐ Our AWESOME team of Teaching Assistants
Graduate
Undergraduate
Laura MagnottiMary Ellen Wiltrout
Nicole CohenJamie DempseyLyle LopezSarah MahoneyTeresa Morales
3‐ UndergraduateReview sectionsOptional
3 Saturday sections 1215 ndash 115Room 110 ‐ A‐G Sarah Room B‐10 ‐ H‐O TeresaRoom 109 ‐ P‐Z Nicole
2 non‐Saturday sectionsHarvard Campus Mondays 6 ndash 7pm
Sever 308 Jamie
Longwood Campus Tuesdays 530‐ 630Kresge 202 Lyle
4‐ Graduate sectionsMandatory
Starts Today
Room 101b ‐ A‐LRoom 103b ‐ M‐Z
5‐ Office hours
Thursday 735‐935 pm 206 Robinson Hall
6‐ Exams and problem sets
Assignment Graduate Undergraduate
Midterm exam 1 100 100
Midterm exam 2 100 100
Final Exam 100 100
Assignment 1 50 50
Assignment 2 50 50
Graduate Assignment 50 ‐
Section 100 ‐
Total points 550 400
Problem sets Turn in at start of class or electronic dropbox
Key posted on following Wednesday
Make‐up exams (1 and 2) No makeup exams will be given without prior notification and approval
Regrades Regrades are only allowed if the exam has beencompleted in pen Regrade requests must be submitted inwriting to the instructor or your TF within 1 week of theexam return Regrade requests should clearly indicatewhich question(s) you are requesting us to review and ajustification of your request
7‐ Course Policies
See syllabus for more details
8‐ Saturday class The Good
9‐ Saturday class The Bad
10‐ The obvious
Chemistry of lifeIntroduction to biochemistry
CarbonHydrogenNitrogenOxygenPhosphorus Sulfate
~ 97 of composition of living organisms
6 simple elements combine to form molecules essential to an organismrsquos existence and function
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
BIOS E‐10 Business
1‐ Course details2‐ Our AWESOME team of Teaching Assistants3‐ Review ldquoundergraduate sectionsrdquo4‐ Graduate sections5‐ Office hours6‐ Exams and problem sets7‐ Course policies (detailed in syllabus)8‐ Saturday classes ndash THE GOOD9‐ Saturday classes ndash THE BAD10‐ The obvious
1‐ Course Details
Suggested textbook Essential Biochemistry Pratt and Cornely‐‐Wiley Plus option‐‐
Alternative Lehninger Principles of Biochemistry (5th edition) Nelson and Cox
Head TA Laura Magnotti
Course email address biocheme10gmailcom
Course website httpisitesharvardeduicbicbdokeyword=k81329amppageid=icbpage434280
2‐ Our AWESOME team of Teaching Assistants
Graduate
Undergraduate
Laura MagnottiMary Ellen Wiltrout
Nicole CohenJamie DempseyLyle LopezSarah MahoneyTeresa Morales
3‐ UndergraduateReview sectionsOptional
3 Saturday sections 1215 ndash 115Room 110 ‐ A‐G Sarah Room B‐10 ‐ H‐O TeresaRoom 109 ‐ P‐Z Nicole
2 non‐Saturday sectionsHarvard Campus Mondays 6 ndash 7pm
Sever 308 Jamie
Longwood Campus Tuesdays 530‐ 630Kresge 202 Lyle
4‐ Graduate sectionsMandatory
Starts Today
Room 101b ‐ A‐LRoom 103b ‐ M‐Z
5‐ Office hours
Thursday 735‐935 pm 206 Robinson Hall
6‐ Exams and problem sets
Assignment Graduate Undergraduate
Midterm exam 1 100 100
Midterm exam 2 100 100
Final Exam 100 100
Assignment 1 50 50
Assignment 2 50 50
Graduate Assignment 50 ‐
Section 100 ‐
Total points 550 400
Problem sets Turn in at start of class or electronic dropbox
Key posted on following Wednesday
Make‐up exams (1 and 2) No makeup exams will be given without prior notification and approval
Regrades Regrades are only allowed if the exam has beencompleted in pen Regrade requests must be submitted inwriting to the instructor or your TF within 1 week of theexam return Regrade requests should clearly indicatewhich question(s) you are requesting us to review and ajustification of your request
7‐ Course Policies
See syllabus for more details
8‐ Saturday class The Good
9‐ Saturday class The Bad
10‐ The obvious
Chemistry of lifeIntroduction to biochemistry
CarbonHydrogenNitrogenOxygenPhosphorus Sulfate
~ 97 of composition of living organisms
6 simple elements combine to form molecules essential to an organismrsquos existence and function
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
1‐ Course Details
Suggested textbook Essential Biochemistry Pratt and Cornely‐‐Wiley Plus option‐‐
Alternative Lehninger Principles of Biochemistry (5th edition) Nelson and Cox
Head TA Laura Magnotti
Course email address biocheme10gmailcom
Course website httpisitesharvardeduicbicbdokeyword=k81329amppageid=icbpage434280
2‐ Our AWESOME team of Teaching Assistants
Graduate
Undergraduate
Laura MagnottiMary Ellen Wiltrout
Nicole CohenJamie DempseyLyle LopezSarah MahoneyTeresa Morales
3‐ UndergraduateReview sectionsOptional
3 Saturday sections 1215 ndash 115Room 110 ‐ A‐G Sarah Room B‐10 ‐ H‐O TeresaRoom 109 ‐ P‐Z Nicole
2 non‐Saturday sectionsHarvard Campus Mondays 6 ndash 7pm
Sever 308 Jamie
Longwood Campus Tuesdays 530‐ 630Kresge 202 Lyle
4‐ Graduate sectionsMandatory
Starts Today
Room 101b ‐ A‐LRoom 103b ‐ M‐Z
5‐ Office hours
Thursday 735‐935 pm 206 Robinson Hall
6‐ Exams and problem sets
Assignment Graduate Undergraduate
Midterm exam 1 100 100
Midterm exam 2 100 100
Final Exam 100 100
Assignment 1 50 50
Assignment 2 50 50
Graduate Assignment 50 ‐
Section 100 ‐
Total points 550 400
Problem sets Turn in at start of class or electronic dropbox
Key posted on following Wednesday
Make‐up exams (1 and 2) No makeup exams will be given without prior notification and approval
Regrades Regrades are only allowed if the exam has beencompleted in pen Regrade requests must be submitted inwriting to the instructor or your TF within 1 week of theexam return Regrade requests should clearly indicatewhich question(s) you are requesting us to review and ajustification of your request
7‐ Course Policies
See syllabus for more details
8‐ Saturday class The Good
9‐ Saturday class The Bad
10‐ The obvious
Chemistry of lifeIntroduction to biochemistry
CarbonHydrogenNitrogenOxygenPhosphorus Sulfate
~ 97 of composition of living organisms
6 simple elements combine to form molecules essential to an organismrsquos existence and function
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
2‐ Our AWESOME team of Teaching Assistants
Graduate
Undergraduate
Laura MagnottiMary Ellen Wiltrout
Nicole CohenJamie DempseyLyle LopezSarah MahoneyTeresa Morales
3‐ UndergraduateReview sectionsOptional
3 Saturday sections 1215 ndash 115Room 110 ‐ A‐G Sarah Room B‐10 ‐ H‐O TeresaRoom 109 ‐ P‐Z Nicole
2 non‐Saturday sectionsHarvard Campus Mondays 6 ndash 7pm
Sever 308 Jamie
Longwood Campus Tuesdays 530‐ 630Kresge 202 Lyle
4‐ Graduate sectionsMandatory
Starts Today
Room 101b ‐ A‐LRoom 103b ‐ M‐Z
5‐ Office hours
Thursday 735‐935 pm 206 Robinson Hall
6‐ Exams and problem sets
Assignment Graduate Undergraduate
Midterm exam 1 100 100
Midterm exam 2 100 100
Final Exam 100 100
Assignment 1 50 50
Assignment 2 50 50
Graduate Assignment 50 ‐
Section 100 ‐
Total points 550 400
Problem sets Turn in at start of class or electronic dropbox
Key posted on following Wednesday
Make‐up exams (1 and 2) No makeup exams will be given without prior notification and approval
Regrades Regrades are only allowed if the exam has beencompleted in pen Regrade requests must be submitted inwriting to the instructor or your TF within 1 week of theexam return Regrade requests should clearly indicatewhich question(s) you are requesting us to review and ajustification of your request
7‐ Course Policies
See syllabus for more details
8‐ Saturday class The Good
9‐ Saturday class The Bad
10‐ The obvious
Chemistry of lifeIntroduction to biochemistry
CarbonHydrogenNitrogenOxygenPhosphorus Sulfate
~ 97 of composition of living organisms
6 simple elements combine to form molecules essential to an organismrsquos existence and function
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
3‐ UndergraduateReview sectionsOptional
3 Saturday sections 1215 ndash 115Room 110 ‐ A‐G Sarah Room B‐10 ‐ H‐O TeresaRoom 109 ‐ P‐Z Nicole
2 non‐Saturday sectionsHarvard Campus Mondays 6 ndash 7pm
Sever 308 Jamie
Longwood Campus Tuesdays 530‐ 630Kresge 202 Lyle
4‐ Graduate sectionsMandatory
Starts Today
Room 101b ‐ A‐LRoom 103b ‐ M‐Z
5‐ Office hours
Thursday 735‐935 pm 206 Robinson Hall
6‐ Exams and problem sets
Assignment Graduate Undergraduate
Midterm exam 1 100 100
Midterm exam 2 100 100
Final Exam 100 100
Assignment 1 50 50
Assignment 2 50 50
Graduate Assignment 50 ‐
Section 100 ‐
Total points 550 400
Problem sets Turn in at start of class or electronic dropbox
Key posted on following Wednesday
Make‐up exams (1 and 2) No makeup exams will be given without prior notification and approval
Regrades Regrades are only allowed if the exam has beencompleted in pen Regrade requests must be submitted inwriting to the instructor or your TF within 1 week of theexam return Regrade requests should clearly indicatewhich question(s) you are requesting us to review and ajustification of your request
7‐ Course Policies
See syllabus for more details
8‐ Saturday class The Good
9‐ Saturday class The Bad
10‐ The obvious
Chemistry of lifeIntroduction to biochemistry
CarbonHydrogenNitrogenOxygenPhosphorus Sulfate
~ 97 of composition of living organisms
6 simple elements combine to form molecules essential to an organismrsquos existence and function
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
4‐ Graduate sectionsMandatory
Starts Today
Room 101b ‐ A‐LRoom 103b ‐ M‐Z
5‐ Office hours
Thursday 735‐935 pm 206 Robinson Hall
6‐ Exams and problem sets
Assignment Graduate Undergraduate
Midterm exam 1 100 100
Midterm exam 2 100 100
Final Exam 100 100
Assignment 1 50 50
Assignment 2 50 50
Graduate Assignment 50 ‐
Section 100 ‐
Total points 550 400
Problem sets Turn in at start of class or electronic dropbox
Key posted on following Wednesday
Make‐up exams (1 and 2) No makeup exams will be given without prior notification and approval
Regrades Regrades are only allowed if the exam has beencompleted in pen Regrade requests must be submitted inwriting to the instructor or your TF within 1 week of theexam return Regrade requests should clearly indicatewhich question(s) you are requesting us to review and ajustification of your request
7‐ Course Policies
See syllabus for more details
8‐ Saturday class The Good
9‐ Saturday class The Bad
10‐ The obvious
Chemistry of lifeIntroduction to biochemistry
CarbonHydrogenNitrogenOxygenPhosphorus Sulfate
~ 97 of composition of living organisms
6 simple elements combine to form molecules essential to an organismrsquos existence and function
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
6‐ Exams and problem sets
Assignment Graduate Undergraduate
Midterm exam 1 100 100
Midterm exam 2 100 100
Final Exam 100 100
Assignment 1 50 50
Assignment 2 50 50
Graduate Assignment 50 ‐
Section 100 ‐
Total points 550 400
Problem sets Turn in at start of class or electronic dropbox
Key posted on following Wednesday
Make‐up exams (1 and 2) No makeup exams will be given without prior notification and approval
Regrades Regrades are only allowed if the exam has beencompleted in pen Regrade requests must be submitted inwriting to the instructor or your TF within 1 week of theexam return Regrade requests should clearly indicatewhich question(s) you are requesting us to review and ajustification of your request
7‐ Course Policies
See syllabus for more details
8‐ Saturday class The Good
9‐ Saturday class The Bad
10‐ The obvious
Chemistry of lifeIntroduction to biochemistry
CarbonHydrogenNitrogenOxygenPhosphorus Sulfate
~ 97 of composition of living organisms
6 simple elements combine to form molecules essential to an organismrsquos existence and function
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Make‐up exams (1 and 2) No makeup exams will be given without prior notification and approval
Regrades Regrades are only allowed if the exam has beencompleted in pen Regrade requests must be submitted inwriting to the instructor or your TF within 1 week of theexam return Regrade requests should clearly indicatewhich question(s) you are requesting us to review and ajustification of your request
7‐ Course Policies
See syllabus for more details
8‐ Saturday class The Good
9‐ Saturday class The Bad
10‐ The obvious
Chemistry of lifeIntroduction to biochemistry
CarbonHydrogenNitrogenOxygenPhosphorus Sulfate
~ 97 of composition of living organisms
6 simple elements combine to form molecules essential to an organismrsquos existence and function
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
8‐ Saturday class The Good
9‐ Saturday class The Bad
10‐ The obvious
Chemistry of lifeIntroduction to biochemistry
CarbonHydrogenNitrogenOxygenPhosphorus Sulfate
~ 97 of composition of living organisms
6 simple elements combine to form molecules essential to an organismrsquos existence and function
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Chemistry of lifeIntroduction to biochemistry
CarbonHydrogenNitrogenOxygenPhosphorus Sulfate
~ 97 of composition of living organisms
6 simple elements combine to form molecules essential to an organismrsquos existence and function
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
CarbonHydrogenNitrogenOxygenPhosphorus Sulfate
~ 97 of composition of living organisms
6 simple elements combine to form molecules essential to an organismrsquos existence and function
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
4 Types of Biomolecules
1‐ Amino Acids
Polypeptide or protein
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
2‐ Carbohydrates (monosaccarides) Disaccharide
Polysaccharide
4 Types of Biomolecules
(CH2O)nngt3
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
3‐ Nucleotides
Nucleic Acids
4 Types of Biomolecules
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
4‐ Lipids
4 Types of Biomolecules
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Why is it advantageous for a cell to link monomers into polymers
Very few molecules can combine in many different ways to produce a wide variety of structures
A cell can get by on a limited amount of raw material
Information contained in the monomers can be stored in the stable form of a polymer
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Each of the macromolecules are organized around which element
1‐ Hydrogen2‐ Oxygen3‐ Carbon4‐ Nitrogen
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Why are cellular organisms carbon based
Bonding versatility
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Only single bonds can rotate freely
Rotation around single bonds allows for different conformations
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Conformation vs configurationConformation Freedom of rotation around a single bond
Different conformations are freely interconvertable
Configuration (stereochemistry) FIXED spatial arrangement of atoms
(same bonds different configuration)
Configuration is conferred by 1‐ double bonds
2‐ chiral centersGeometric Isomers
EnantiomersDiasteromers
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Geometric isomers or cis‐trans isomersDiffer in arrangement of groups with respect to a non‐rotating double bond
Geometric isomers cannot be interconverted without breaking double bonds requires energy
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
NonsuperimposableChiral
Enantomer
SuperimposableAchiral
Identical Structures
‐An atom attached to 4 different groups is a chiral center (asymmetric C)
‐A molecule is chiral if it cannot be superimposed on its mirror image
‐All chiral molecules contain at least one chiral center
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Stereochemistry due to chiral centers4 different substituents bonded to a carbon may
be arranged in 2 different ways in space (2 configurations)
Enantiomers 2 stereoisomers that are mirror images
Diastereomers 2 stereoisomers that are not mirror images
Enantiomers (mirror image) Diastereomers (non‐mirror image)
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
How many chiral carbons are therein D‐Ribulose
n chiral carbons gives 2n stereoisomers
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Common functional groups found in biochemistry
Amino
CH3Methyl
Hydroxyl
Sulfhydryl
Acyl group
Carbonyl
Carboxyl
Ester
Phosphoester
Phosphoanhydride
Phosphoryl
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Energy and ThermodynamicsStudy of heat and power
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
A living organism is an open systemExchanges both matter and energy with its surroundings
Organisms derive energy from the surroundingsTake up chemical fuels (glucose)
or Absorb energy from sunlight
Organisms convert energy to produce work
Return some energy to the surroundings as heat
Release end product molecules that are less well organized than the starting fuel
Total energyRemains constant
Entropyor disorderincreases
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
2 Laws of Thermodynamics
Energy cannot be created or destroyed but can change forms
Example A river flowing over a damenergy is harnessed as electricity andand used to produce heat or perform work
First Law Conservation of energy
The energy in the universe remains constant
Energy = the ability to do work mechanical potential electrical chemical
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Second law The entropy of the universe increases2 Laws of Thermodynamics
Entropy a measure of a systemrsquos disorder or randomness
Implications for biochemistryNaturally occurring (spontaneous) processes will always proceed towards the state with the least potential energyNaturally occurring (spontaneous) processes must increase the disorder in the universe
Thermodynamics tell us if a reaction is possible and whether it will occur spontaneously
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Synthesis of MacromoleculesSpontaneous or not
Building organisms require energy
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Thermodynamics and Gibbs free energy
Gibbs free energy (G) usable energy content of a biological system ndash Joules per mol (Jmol‐1)
Gibbs free energy
Enthalpy (H)‐heat content of the system
Reflects the number and kinds of bonds
Entropy (S)‐ measure of disorder
G = H‐T S
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Does a process occur spontaneously or not
G gt 0 = not spontaneous Endergonic ‐ require input of energy
G lt 0 = spontaneous Exergonic ‐ release free energy
G = 0 = equilibrium No net change in the energy of the system
∆G does NOT indicate how fast the reaction will proceed (rate) ‐only whether it will occur
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
G = H‐T S
Effects of H and S on spontaneity
∆H ∆S ∆G = ∆H‐ T∆S
‐ + release of heat increase in entropy ‐spontaneous at all temps
‐ ‐ release of heat decrease in entropy ndashspontaneity depends on temp
+ + increase in heat increase in entropy spontaneity depends on temp
+ ‐ increase in heat decrease in entropy unfavorable at all temps
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Letrsquos consider Gibbs Free Energy in terms of chemical reactions
The entropy of a substance increases with itrsquos volumeexample gas molecules
Entropy is therefore a function of concentration
If entropy changes with concentration so must free energy
The free energy change of a chemical reaction depends on the concentrations of reactants and products
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Chemical equilibria and free energy
A reactionrsquos free energy change depends on 2 things1) A constant term dependent only on the reaction itself2) A variable term dependent on concentration of
reactants and products
A + B C + D
When a reaction is at equilibrium
Keq = [C]eq[D]eq[A]eq[B]eq
Equilibrium constant
Equilibrium ‐ No net change in [ ] of reactantsEquilibrium DOES NOT mean that the [ ] of reactants and products are =
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Concentrations = 10 MTemp = 25degCPressure = 1 atm
Chemical equilibria and free energy
ΔGdegrsquo ‐ Standard Free energy change of a reactionunder standard conditions
When not at equilibrium the reactants experience a driving force to reach equilibrium
∆Gdegrsquo = ‐ RT ln Keq
Both ∆Gdegrsquo and Keq are constant for a particular reaction
R = gas constantT = temperature
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
∆G = ∆Gdegrsquo + RT ln [C][D] [A][B]
R = gas constantT = temperature
But ‐ biochemical rxns donrsquot occur at standard stateWe need to factor in the variable components
∆G is a function of the actual concentrations of reactants and the temperature
A reaction with a + ∆Gdegrsquo (nonspontaneous under standard conditions) may proceed in vivo depending on the concentration of reactants
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
1 ‐ You can make an unfavorable reaction favorable by adjusting the [ ] of reactants and products
Dihydroxyacetone (DHAP) Glyceraldehyde 3‐ phosphate (GAP)
When at equilibrium the reaction is endergonic (∆Gdeg lsquo = 75 kJmol)DHAP will not spontaneously convert to GAP
When [GAP] decreases DHAP will spontaneously convert to GAP
Phosphate
[DHAP] [GAP]
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Many of lifersquos chemical reactions are unfavorableHow do we drive these reactions to occur
2 ‐We couple endergonic reactions with exergonic reactions
Unfavorable Favorable
A rarr BC rarr D
∆G = + 15 kJM‐1
∆G = ‐ 20 kJM‐1
= ‐ 5 kJM‐1 Reaction is now favorableA + C rarr B + D
Cells can enable unfavorable reactions by coupling them with favorable reactions (eg ATP hydrolysis)
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Real life exampleHow do we make large ordered proteins from individual amino acids
∆G = positive (endergonic)Amino Acids rarr Proteins
ATP rarr AMP + P ‐ P ∆G = negative (exergonic)
By coupling thermodynamically unfavorable processes with sources of high energy cells are able to synthesize large polymers
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Living organisms and steady state
Remember living organisms are ldquoopen systemsrdquo and exchange matter and energy with the surroundings
We continuously ingest high enthalpy low entropy nutrients and convert them to low enthalpy high‐entropy waste products
Living organisms only come to equilibrium when this process isdisrupted
Equilibrium = Death
However we do maintain a steady state or homeostasis ‐Properties of the cell are maintained over time
The system reacts to changes in these properties to restore homeostasis
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Chemistry of WaterStudy of an aqueous environment
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Aqueous solutions and properties of water
1‐ Organisms are mostly water (human 70)
2‐ Influences the shape and function of biomolecules
3‐Medium of most biochemical reactions
4‐ Important for transport of nutrients and waste
5‐Water may itself participate in chemical reactions
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
O forms covalent bonds with 2 H atoms
H20 has 2 unshared pairs of electrons
O is more electronegative than the Hrsquos (O has a stronger attraction for the electrons)
Unequal electron sharing between the O and the Hrsquos ‐ tetrahedral
This creates a dipole or polarity where the O has a partial ‐ charge and the Hrsquoshave a partial + charge
Structure of H20
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
H‐bonds result from attraction between the O atom of 1H2O molecule and the H atom of another water molecule
Hydrogen Bonding
H‐ bonds result in cohesiveness and high surface tension ofwater
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Structure of Ice ‐ H2O participates in 4 hydrogen bonds
Donates to H bonds
Accepts H bonds
Regular lattice‐like structure
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Hydrogen bonding in H2O depends on the phase
No H bonds ~ 34 H bonds 4 H bonds
H20 molecules are in continuous motion ndashH‐ bonds are randomly breaking and forming
At room temperature why does ice melt spontaneouslyWhat would ∆G be What would ∆S be
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Hydrogen bonds are not unique to water
N ‐ H O ndash H S ‐ H
C ndash H bonds do not form hydrogen bonds
Common H bonds
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Other types of bonds in biochemistry
Covalent Atoms share electrons
Ionic One atom donates anelectron to another atomcreating opposite charges
Van der WaalsWeak attraction between 2 polar non‐chargedparticles (unequaldistribution of charges)
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Relative strengths of different bonds
Non covalent interactions are individuallyweak but strong in large numbers
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Water as a solvent
Interactions between H2O molecules and the ions gtgt interactions between Na and Cl
Polar water molecules surround ions by aligning their partial charges with oppositely charged ions
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Polar ndash hydrophilic ndash soluble in water ndash charged or able to H bond
Nonpolar ndash hydrophobic ndash insoluble in water
Amphiphilic ndash contains both polar and nonpolar components
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
BP Oil Spill
APolarBNonpolarCAmphiphilic
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
APolarBNonpolarCAmphiphilic
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Ordered H2O formscages around hydrophobic portion
Polar head
Hydrophobic tailscluster less orderedwater
Hydrophobic tailssequester from waterOrdered water is minimal
Entropy increases as H20 becomes less ordered
Hydrophobic effect
Entropy
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
The hydrophobic effect is very important in protein folding
The hydrophobic effect drives the nonpolar components to cluster away from the water and effectively increases the amount of disordered water
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Entropy also plays a role in polar enzyme‐substrate interactions
Binding of substrate to enzymereleases some of the ordered water
Thermodynamic push towardsthe formation of the enzyme‐substrate complex
Also important inhormone‐ligand interactions
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Acid Base Chemistry
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Why talk about acids and bases
Many biological molecules have functional groups that undergo acid-base reactions therefore the properties of these molecules are affected by acidity of the solutions in which they are surrounded
pH affects the structure and activity of biological molecules
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Water in chemical reactions
H20 H⁺ + OH⁻
Proton
Protons exists as hydronium ionsin solution
Hydronium ion gives up a proton
Water acceptsa proton becominga hydronium ion
Protonjumping
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Keq = [H⁺][OH⁻][H20]
Ionization of Water
Kw = Keq[H2O] = 10 x 10‐14
Keq and [H20] are constant andare redefined as Kw ndashionization constant of water
Kw = 10‐14 = [H⁺][OH‐] Because Kw is constant the [H⁺] and [OH⁻] must balance each other
Neutral solu on= [H⁺] = [OH‐] = 10 ‐7 (pure water)Acidic solu on= [H⁺] gt 10 ‐7
Basic solution = [H+] lt 10 ‐7
H20 H⁺ + OH⁻
Dissociation constant
Keq[H2O] = [H⁺][OH‐]
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
pH = ‐log [H+]
[H⁺] = [OH‐] = 10 ‐7
[H⁺] gt 10 ‐7
[H+] lt 10 ‐7
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Acids and Bases ‐ Act to alter the pH of a solution
Acid ndash proton donorsBase ndash proton acceptor
Strong acids and bases (HCL and NaOH) ndash ionize completely
HCl donates a proton (H+) increasing the [H+] of the solution = decreases pH
NaOH accepts a proton decreasing the [H+] of the solution = increases pH
HCL + H20 H3O + + Cl‐
NaOH + H30 Na+ + 2H20
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
‐ubiquitous in biological systems‐play an important role in metabolism and its regulation
Weak acid and bases
Weak acids and bases do not dissociate completely in H2OTendency of an acid to lose its proton is defined by Keq or Ka
HA H+ + A‐
Keq = [H+][A‐][HA]
Acid Conjugate base
= Ka Acid dissociation constant
pK = ‐ log KaThe larger the acidrsquos Ka the smaller itrsquos pK and the greater itrsquos strength
‐‐ stronger tendency to lose a proton‐‐
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Determining the pH of a solutionHenderson ndash Hasselbach equation
Relates the pH of a solution to the pK of an acidand the [HA] and [A‐]
pH = pK + log [A‐][HA]
When the pH of an acid is equal to the pK of that acid then the acid is half dissociated [A‐] = [HA]
When pH lt pK then [HA] gt [A‐]When pH gt pK then [HA] lt [A‐]
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
pH Buffers
Various aspects of biological systems work best at well‐defined pHs
Buffers mop up excessive hydrogen ions or hydroxide ions keeping pHs within well‐defined ranges
Enzymes have optimum pHrsquos ‐ enzymes donrsquot function ‐ reactions slow ‐ organism dies
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
pH buffering ndash titration of a weak acid
1‐ Prior to tritration all the acidis in protonated form (HA)
2‐ Added base causes protonsto dissociate from the acidproducing A‐ until all the acid is in its conjugate base
3‐ At the midpoint
[HA] = [A‐]pH = pK
4‐ Buffering occurs one pH unitabove and below the pK
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Biological BufferingBicarbonate system ndash maintains blood pH
H+ + HCO‐3 H2CO3 H2O + CO2
Carbonic acid
Bicarbonate
H+ = buffered by reaction with bicarbonate to form carbonic acid= eliminated by kidneys
CO2 = buffered by the amount of CO2 giving off by the lungs (alteration of breathing ndash controlled by brainstem sensing of pH )
Timing of buffering capacityRegulation by breathing ndash minutes to hoursRegulation by kidney function ndash hours to days
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
H+ + HCO‐3 H2CO3 H2O + CO2
What happens in metabolic acidosis
Blood pH decreases due to an accumulation of H+
How does the body attempt to quickly adjust for the acidosis
Increased ventilation ldquoblowing offrdquo CO2
How does losing CO2 decrease the amount of H+
Shifts the equilibrium of the equation towards making CO2Which decreases the amount of H+
H+ + HCO‐3 H2CO3 H2O + CO2
Le Chateliersprinciple
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Introduction to Amino Acids
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
General Structure of Amino Acids
carbonCarboxyl groupAmino group Variable R group
Common to all AAs
R groups differ bySize
Charge20 Standard Amino Acids
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Categorization of Amino Acids by R groups
Interior of proteins where they do not interact with water
Side chains seldom participate in chemical reactions
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Categorization of Amino Acids by R groups
Polar side chains can interact with water because they contain hydrogen‐bonding groups
Glycine cannot form hydrogen bonds but is listed as polar because It is neither hydrophobic nor charged (other sources have it as nonpolar)
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Categorization of Amino Acids by R groups
Side groups are always charged under physiological conditions
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Histidine can accept a protein to form an imidazolium ion (acid)Can act as acid or base
Certain polar‐uncharged amino acids can become charged depending on the environment
Histidine is very versatile in catalyzing chemical reactions ndashvery often in the active sites of enzymes
AA characteristics important for protein structure or function
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Cysteine can form disulfide bonds
Cysteine can be oxidized to form a disulfide bond
Very important for protein structure covalent links between polypeptide chains
AA characteristics important for protein structure or function
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Amino Acids are ChiralException is Glycine
L‐ Enantiomer D‐ Enantiomer
All AA residues in proteins are in the L‐configuration
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Amino acids have characteristic titration curves
‐Every AA has at least 2 ionizablegroups COOH and NH3+
‐AAs with ionizable R groups will have 3
‐Each ionizable group will have a 1) pKa (pKa ndash measure of the
tendency to lose a proton)
2) region of buffering capacity
‐ Ionizable groups act as acids with uarr pH (give up protons)
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Amino acids have characteristic titration curves
1‐ Low pH ( ltpK1) = AA is fully protonatedCharge = +1
3‐ pI = Removal of 1st proton is completeRemoval of 2nd proton has begunldquoZwitterionrdquoCharge = 0
2‐ pK1 = [COOH] = [COO‐]
4‐ pK2 = [NH3+]=[NH2]
5‐ High pH ( gtpK2) = AA is fully deprotonatedCharge = ‐1
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
How would you calculate the pI of Glycine
pI = average of pK1 and pk2
of Glutamate
+1 0 ‐1 ‐2
pI = frac12 (pK1 + pKR)
+1 0 ‐1
Find point of 0 charge and calculate theaverage of 2 pKs surrounding 0 charge
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Ionization of HistidineCalculate the fraction of histidine that has is imidazole side chain protonated atpH 73
pH 73 = carboxyl is fully deprotonated (COO‐)amino group is fully protonated (NH3+)imidazole group is partially dissociated
pH = pka + log [A‐][HA]
73 = 60 + log [deprot imidazole][prot imidazole]
13 = log [deprot imidazole][prot imidazole]
Antilog 13 = [deprot imidazole][prot imidazole]
= 20 x 101
= 20 x 101
= 20 = deprot1 prot
Fraction of Protonated = 121 = 48
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Yes you need to know
1‐ Nomenclature (1 3 letter codes)2‐ Properties of R groups3‐ Recognize structures
No you will not have to draw structures
Amino Acids
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Proteins and protein structures
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Proteins are comprised of a wide variety of monomers and withvaried charge distribution
Comparison to DNA which has a characteristic structure (double helix) and is comprised of similarly shaped and charged monomers
Proteins have the most diverse properties of all biological polymers and have an incredible number of functions
Proteins Amino Acid polymers
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Some important functions of proteins
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Protein 3D structure depends on the primary sequence of AAs
Question What happens if you change a single amino acid in the primary sequence
Small changes at the amino acid level can affect structure Sickle Cell Anemia
Small changes at the amino acid level can affect structure Sickle Cell Anemia