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BIOCHEMISTRY

Water and pH

Water

-unique properties:

>ability to solvate a wide range of organic and inorganic

molecules

>dipolar structure

>exceptional capacity for forming hydrogen bonds

>excellent nucleophile (reactant/product in many metabolic

reactions)

-regulation of water balance

>hypothalamic mechanisms

>controls thirst

>antidiuretic hormone (ADH)

>retention/excretion of water by kidneys

>evaporative loss

*Nephrogenic Diabetes Insipidus

-involves the inability to concentrate urine or adjust to

subtle changes in ECF osmolarity

-results from the unresponsiveness of renal tubular osmoreceptors to ADH

Acidity

-concentration of protons

-reported using the logarithmic pH scale

Bicarbonate (and other buffers)

-maintain ECF between 7.35-7.45

Acid-Base Balance disturbances

-verified by measuring pH of arterial blood and the CO2 content of venous blood

Acidosis

-blood pH 7.45

-vomiting of acidic gastric contents

WATER IS AN IDEAL BIOLOGIC SOLVENT

Water molecules

-form dipoles

-irregular, slightly skewed tetrahedron with oxygen at its center and the two hydrogens and the undshared electrons of the remaining two sp3-hybridized orbitals occupy the corners of the tetrahedron -105angle between hydrogen (Normal tetrahedral angle: 109.5) Ammonia is also tetrahedral, 107 angle between its hydrogens.

-strongly electronegative oxygen:

>attract electrons away from the hydrogen nuclei

>leave a partial positive charge

>two unshared electron pairs constitute a region of local

negative charge

Dipole- a molecule with electrical charge distributed

asymmetrically about its structure

-strong dipole: responsible for its high dielectric

constant

*Coulombs Law- the strength of interaction (F) between oppositely charged particles is INVERSELY PROPORTIONATE to

the dielectric constant () Dielectric constants:

>hexane: 1.9

>ethanol: 24.3

>water: 78.5

-water greatly decreases the force of attraction between

charged and polar species relative to water-free

environments with lower dielectric constants

-strong dipole + high dielectric constant = enable water

to dissolve large quantities of charged compounds

-form hydrogen bonds

>partially unshielded hydrogen nucleus covalently bound to

an electron-withdrawing oxygen/nitrogen atom can interact

with an unshared electron pair on another oxygen/nitrogen

atom

*hydrogen bonding

-influences physical properties of water

-accounts for it exceptionally high viscosity, surface

tension, and boiling point

-to rupture in liquid water: 4.5 kcal/mol

Hydrogen acceptors:

>oxygen atoms of aldehydes

>..ketones

>..amides

Hydrogen acceptors and donors:

>alcohols

>carboxylic acids

>amines

INTERACTION WITH WATER INFLUENCES THE STRUCTURE OF

BIOMOLECULES

Covalent bond

-strongest force that holds molecules together

Noncovalent forces

-of lesser magnitude

-make significant contributions to the structure, stability, and functional competence of macromolecules in living cells

-can be either attractive or repulsive

Amphipathic biomolecules

-possess regions rich in charged or polar functional

groups as well as regions with hydrophobic character

>Amino Acids: arginine, glutamate, serine

>phospholipid bilayer (membrane)

-maximizes opportunities for the formations of

energetically favourable charge-dipole, dipole-dipole, and

hydrogen bonding interactions between polar groups on the

biomolecule and water

-minimizes energetically unfavourable contacts between

water and hydrophobic groups

Hydrophobic interactions

-tendency of nonpolar compounds to SELF-ASSOCIATE in an

aqueous environment

-Self association minimizes disruption of energetically

favourable interactions between the surrounding water

molecules

-water molecules adjacent to a hydrophobic group are

restricted in the number of orientations (degrees of

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freedom) that permit them to participate in the maximum

number of energetically favourable hydrogen bonds

-Maximal formation of multiple hydrogen bonds maximizes

enthalpy decreases entropy [maintained by increasing

the order of adjacent water molecules]

2nd Law of Thermodynamics

-the optimal free energy of a hydrocarbon-water mixture is

a function of both maximal enthalpy (hydrogen bonding) and

minimum entropy (maximum degrees of freedom)

Salt Bridges

-electrostatic interactions between oppositely charged

groups within or between biomolecules

-comparable in strength to hydrogen bonds

-act over larger distances

-facilitate the binding of charged molecules and ions to

proteins and nucleic acids

Van der Waals Forces

-arise from attractions between transient dipoles

-generated by the rapid movement of electrons of all

neutral atoms

-weaker than hydrogen bonds

-potentially extremely numerous

-act over very short distances

DNA double helix

-individual DNA strand:covalent bonds

-two strands of the helix: noncovalent interactions

>Watson-Crick base pairing: hydrogen bonds between

nucleotide bases

>van der waals interactions between stacked purine and

pyrimidine bases

-presents the charged phosphate groups and polar hydroxyl

groups from the ribose sugars of the DNA backbone to water

while burying the relatively hydrophobic nucleotide bases

inside

-extended backbone: maximizes the distance between

negatively charged phosphates, minimizing unfavourable

electrostatic interactions

WATER IS AN EXCELLENT NUCLEOPHILE

-waters two lone pairs of sp3 electrons bear a partial negative charge

Nucleophiles

-electron-rich molecules

Electrophiles

-electron-poor molecules

Other nuleophiles

>oxygen atoms of phosphates

>..alcohols

>..carboxylic acids

>sulphur of thiols

>nitrogen of amines

>imidazole of histidine

Common electrophiles

>carbonyl carbons in amides

>esters

>aldehydes

>ketones

>phosphorus atoms of phosphoesters

Hydrolysis

-Nucleophilic attack by watercleavage of amide,

glycoside, ester bonds (-hold biopolymers together)

-thermodynamically favoured reaction

>the amide and phosphoester bonds of polypeptides and

oligonucleotides are stable in the aqueous environment of

the cell

>governs equilibrium of reaction but do not determine the

rate at which it will proceed

Enzymes

-protein catalysts

-accelerate the rate of hydrolytic reactions when needed

-surmounts barriers by directly linking two normally

separate reactions together

Proteases

-catalyze the hydrolysis of proteins into their component

amino acids

Nucleases

-catalyze the the hydrolysis of the phosphoester bonds in

DNA and RNA

Monomer units are joined together to form

biopolymers(CHONs, glycogen)water Ex: formation of peptide bond between two amino acids

Hydrolysis and Phosphorolysis of Glycogen

-involve the transfer of glucosyl groups to water or to

orthophosphate

Equilibrium constant for the hydrolysis of covalent bonds

-favors the formation of split products

Group transfer reactions responsible for the biosynthesis

of macromolecules

-involve thermodynamically unfavored covalent bond

formation

Energetically unfavourable group transfer reaction +

thermodynamically favourable group reactioncouple

reaction

-net overall change in free energy favors biopolymer

synthesis

Precise and differential control of enzyme activity and

the sequestration of enzymes in specific organelles

determine under what physiologic conditions a given

polymer will be synthesized or degraded

Water can act both as an acid and a base

-its ionization may be represented as an intermolecular

proton transfer hydronium ion (H3O+) and hydroxide ion

(OH-)

H3O+ and OH

- continuously recombine to form water molecules

-an individual hydrogen or oxygen cannot be stated to be

present as an ion or as part of a water molecule

1 gram of water= 3.46 x 1022 molecules

-for every hydrogen ion or hydroxide ion in pure water,

there are 1.8 x 10-9 water molecules (product of

probability that a hydrogen in pure water exists as a

hydrogen ion)

K=Dissocation constant

Brackets=represent molar concentrations

K= [H+][OH

-]

--------

[H2O]

1 mole of water= 18 g

1 Liter (1000 g) of water = 55.56 mol (pure water)

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Molar conc. of H+ ions(or of OH

- ions) in pure water=

product of probability X the molar conc. of water

1.0 x 10-7 mol/L = 1.8 x 10

-9 x 55.56 mol/L

K= [10-7] [

10-7] = 0.018 x 10

-14 = 1.8x 10

-16 mol/L

----------

[55.56]

Kw = ion product for water

= (K) [H2O] = [H+] [OH

-]

= (1.8x 10-16 mol/L) x (55.56 mol/L)

= 1.00 x 10-14 (mol/L)

2

= [H+] [OH

-]

pH IS THE NEGATIVE LOG OF THE HYDROGEN ION CONCENTRATION

pH

-negative log of the hydrogen ion concentration

= -log[H+]

-To calculate:

1. Calculate the hydrogen ion concentration [H+].

2. Calculate the base 10 logarithm of [H+].

3.pH is the negative of the value in step 2.

-low pH: high conc. of H+

-high pH: low conc. of H+

Acids

-proton donors

-protonated species

-low pH

Bases

-proton acceptors

-high pH

Strong acids

-completely dissociate into anions and protons even in

strongly acidic solutions

Weak acids

-dissociate only partially in acidic solutions

-conjugate: strong base

Strong bases

-completely dissociate even at high pH

-conjugate: weak acid

pOH = -log[OH-]

Kw = [H+] [OH

-] = 10

-14

log[H+] + log[OH

-] = log10

-14 pH + pOH = 14

Carboxyl, amino and phosphate groups

-present in proteins and nucleic acids, most coenzymes,

and most intermediart metabolites

Conjugate base

-uprotonated species

the stronger the acid, the lower is its pKa value

pKa -used to express the relative strengths of both acids and

bases

-(-log Ka)

=pH

Acid = conjugate base [H+] = Ka

Henderson-Hasselbalch Equation:

pH= pKa + log [A-]/[HA]

Buffering

-the ability to resist change in pH following addition of

strong acid or base

Oxidative Metabolism

-produces carbon dioxide (anhydride of carbonic acid)

-CO2 if not bufferedacidosis

-maintenance of constant pH

>buffering by phosphate, bicarbonate, and proteins

>accept or release protons to resist change in pH

Tissue Extracts/Enzymes Experiments

-buffers:

>MES ([2-N-morpholino]-ethanesulfonic acid)

>inorganic orthophosphate

>HEPES (N-hydroxyethylpiperazine-N-2-ethanesulfonic acid)

>Tris (tris[hydroxymethyl]aminomethane]

Acid Strength

-presence of adjacent negative charge hinders the release

of a proton from a nearby group, raising its pKa

-adjacent charge decreases with distance

pKa value

-medium may either raise or lower pKa depending on whether

the undissociated acid or its conjugated base is the

charged species

-ethanol decreases the ability of water to solvate a

charged species

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Carbohydrates of Physiologic Significance

Carbohydrates

-Plants

>glucose is synthesized from carbon dioxide and water by

photosynthesis

>stored as starch

>used to synthesize cellulose of the plant cell walls

-Animals:

>can be synthesized from amino acids

>most are derived ultimately from plants

Glucose

-most important carbohydrate

-most dietary carbohydrate is absorbed into the

bloodstream as glucose

-formed by hydrolysis of dietary starch and disaccharides

-converted to glucose in the liver

-major metabolic fuel of mammals

-universal fuel of the fetus

-precursor for synthesis of all the other carbohydrates in

the body

-with 4 asymmetric carbon atoms

-can form 16 isomers

Other carbohydrates:

>glycogen: for storage

>ribose and deoxyribose: in nucleic acids

>galactose: for synthesis of lactose in milk; in

glycolipids

>glucose in combination with protein: glycoproteins and

proteoglycans

Diseases associated with carbohydrate metabolism

>Diabetes mellitus

>galactosemia

>glycogen storage diseases

>lactose intolerance

Monosaccaharides

-sugars that cannot be hydrolyzed into simpler

carbohydrates

-trioses, tetroses, pentoses, hexoses, heptoses: number of

carbon atoms

-aldoses or ketoses: aldehyde or ketone group

-most of the naturally occurring monosaccharides are D

sugars

-enzymes responsible for their metabolism are specific for

D isomer configuration

Trioses

>Glycerose (glyceraldehyde)

>dihydroxyacetone

Tetroses

>erythrose

>erythrulose

Pentoses

>Ribose

>ribulose

Hexoses

>Glucose

>fructose

Heptoses

>Sedoheptulose

Aldoses

>Glycerose

>Erythrose

>Ribose

>Glucose

Ketoses

>Dihydroxyacetone

>Erythrulose

>Ribulose

>Sedoheptulose

Polyhydric alcohols

-sugar alcohols

-polyols

-aldehyde/ketone group has been reduced to an alcohol

group

-synthesized by reduction of monosaccharides

-for use in the manufacture of foods for weight reduction

and for diabetics

-poorly absorbed

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-have about half the energy yield of sugars

Disaccharides

-condensation products of two monosaccharide units

>lactose

>maltose

>sucrose

>trehalose

Oligosaccharides

-condensation products of 3-10 monosaccharides

-most are not digested by human enzymes

Polysaccharides

-condensation products of more than 10 monosaccharide

units

>starches

>dextrins

-may be linear or branched polymers

-hexosans or pentosans

nonstarch polysaccharides in food

-not digested by enzymes

-major component of dietry fiber

>cellulose (glucose polymer)

>inulin (fructose polymer): storage carbohydrate in some

plants

Structures of glucose

>straight chain

>cyclic structure:

-hemiacetal formed by reaction between the aldehyde group

and a hydroxyl group

>chair form

Haworth Projection

-the molecule is viewed from the side and above the plane

of the ring

D and L isomerism

-determined by its spatial relationship to the parent

compound of the carbohydrates (glyceraldehyde: 3-carbon

sugar glycerose)

-orientation of H and OH groups around the carbon atom adjacent to the terminal primary alcohol carbon (carbon 5

in glucose) determines whether the sugar belongs to the D

or L series

D isomer

- (-OH) group on the carbon is on the right

L isomer

- (-OH) group on the carbon is on the left

Optical Activity

-plane polarized light is passed through a solution of an

optical isomer, it rotates either to the right or to the

left

-direction of rotation of polarized light is independent

of the stereochemistry of sugar

Dextrorotatory(+)

-rotates to the right

Levarotatory(-)

-rotates to the left

Pyranose and furanose ring structures

-pyran: six membered ring

-furan: five membered ring

Alpha and Beta Anomers

-aldose: hemiacetal

-ketose: hemiketal

Epimers

-isomers differing as a result of variations in

configuration of the OH and H on carbon atoms 2, 3, and 4 of glucose

-most important epimers of glucose:

>mannose (at carbon 2)

>galactose (at carbon 4)

Aldose-ketose isomerism

-fructose has the same molecular formula as glucose

-fructose differs from glucose in its structure

Pentoses

-important in nucleotides, nucleic acids, and several

coenzymes

Most important hexoses

>glucose

>galactose

>fructose

>mannose

Biochemically important ketoses