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Biochemistry-IBiochemistry-I

Dr. Moayad H. KhataibehDr. Moayad H. KhataibehHead, Department of Head, Department of

PharmacologyPharmacologyCollege of PharmacyCollege of Pharmacy

Alkharj UniversityAlkharj University

Welcome to:Welcome to:

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PHL 213 = Biochemistry-I, 2 (2+0).PHL 213 = Biochemistry-I, 2 (2+0).

The course deals with the following topics The course deals with the following topics in biochemistry: amino acids and proteins in biochemistry: amino acids and proteins including enzymes, biological oxidation, including enzymes, biological oxidation, porphyrins and nucleic acids. The effects porphyrins and nucleic acids. The effects of certain xenobiotics (foreign chemicals) of certain xenobiotics (foreign chemicals) including drugs and toxic agents on including drugs and toxic agents on molecular level and the basis of their molecular level and the basis of their clinical impact are emphasized whenever clinical impact are emphasized whenever possible.possible.

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Definition and Scope:Definition and Scope:

The study of the substances and chemical processes which The study of the substances and chemical processes which occur in living organisms. It includes the identification and occur in living organisms. It includes the identification and quantitative determination of the substances, studies of quantitative determination of the substances, studies of their structure, determining how they are their structure, determining how they are synthesizedsynthesized and and degradeddegraded in organisms, and elucidating their role in the in organisms, and elucidating their role in the operation of the organism. operation of the organism.

Substances studied in biochemistry include Substances studied in biochemistry include carbohydratescarbohydrates (including simple sugars and large polysaccharides), (including simple sugars and large polysaccharides), proteins (such as enzymes), ribonucleic acid (RNA) and proteins (such as enzymes), ribonucleic acid (RNA) and deoxyribonucleic aciddeoxyribonucleic acid (DNA), lipids, minerals, vitamins, and (DNA), lipids, minerals, vitamins, and hormoneshormones. .

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Chapter-I : Chapter-I : WaterWater Must understand water and its properties.Must understand water and its properties. Why? Macromolecular components (i.e. proteins) assume shapes in Why? Macromolecular components (i.e. proteins) assume shapes in

response to water.response to water. Most metabolic machinery operates in an aqueous environment.Most metabolic machinery operates in an aqueous environment.

Properties of WaterProperties of Water1.1. PolarityPolarity2.2. Hydrogen bondsHydrogen bonds 3.3. Universal solventUniversal solvent 4.4. Hydrophobic interactionsHydrophobic interactions5.5. Other noncovalent interactions in biomoleculesOther noncovalent interactions in biomolecules

i.i. hydrogen bondshydrogen bonds ii.ii. hydrophobic interactionshydrophobic interactions iii.iii. charge-charge interactions or electrostatic interactions (ionic bonds)charge-charge interactions or electrostatic interactions (ionic bonds)

iv.iv. van der Waals forcesvan der Waals forces

6.6. Nucleophilic nature of waterNucleophilic nature of water7.7. Ionization of waterIonization of water8.8. pH scalepH scale

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1) 1) PolarityPolarity

Covalent bonds (electron pair is shared) between Covalent bonds (electron pair is shared) between oxygen and hydrogen atoms with a bond angle of oxygen and hydrogen atoms with a bond angle of

104.5104.5°°.. Oxygen atom is more electronegative that Oxygen atom is more electronegative that

hydrogen atom --> electrons spend more time hydrogen atom --> electrons spend more time around oxygen atom than hydrogen atom --> around oxygen atom than hydrogen atom --> result is a POLAR covalent bond.result is a POLAR covalent bond.

Creates a permanent dipole in the molecule.Creates a permanent dipole in the molecule. Can determine relative solubility of molecules Can determine relative solubility of molecules

“like dissolves like”.“like dissolves like”.

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3. 3. Universal solventUniversal solvent ((Solvent of lifeSolvent of life))

Water can interact with and dissolve other polar compounds Water can interact with and dissolve other polar compounds and those that ionize (electrolytes) because they are and those that ionize (electrolytes) because they are hydrophilic.hydrophilic.

Do so by aligning themselves around the electrolytes to form Do so by aligning themselves around the electrolytes to form solvation spheressolvation spheres - shell of water molecules around each - shell of water molecules around each ion.ion.

Solubility of organic molecules in water depends on polarity Solubility of organic molecules in water depends on polarity and the ability to form hydrogen bonds with water.and the ability to form hydrogen bonds with water.

Functional groups on molecules that confer solubility:Functional groups on molecules that confer solubility:carboxylatescarboxylatesprotonated aminesprotonated aminesaminoaminohydroxylhydroxylcarbonylcarbonyl

As the number of polar groups increases in a molecule, so As the number of polar groups increases in a molecule, so does its solubility in water.does its solubility in water.

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22. . Hydrogen bondsHydrogen bonds Due to polar covalent bonds --> attraction of water Due to polar covalent bonds --> attraction of water

molecules for each other.molecules for each other. Creates hydrogen bonds = attraction of one slightly Creates hydrogen bonds = attraction of one slightly

positive hydrogen atom of one water molecule and positive hydrogen atom of one water molecule and one slightly negative oxygen atom of another water one slightly negative oxygen atom of another water molecule.molecule.

The length of the bond is about twice that of a The length of the bond is about twice that of a covalent bond.covalent bond.

Each water molecule can form hydrogen bonds with Each water molecule can form hydrogen bonds with four other water molecules. Weaker than covalent four other water molecules. Weaker than covalent bonds (about 25x weaker).bonds (about 25x weaker).

Hydrogen bonds give water a Hydrogen bonds give water a high melting pointhigh melting point.. Density of water decreases as it cools --> water Density of water decreases as it cools --> water

expands as it freezes--> ice results from an open expands as it freezes--> ice results from an open lattice of water molecules --> less dense, but more lattice of water molecules --> less dense, but more ordered.ordered.

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22. . Hydrogen bonds (cont.).Hydrogen bonds (cont.).

Hydrogen bonds contribute to water’s Hydrogen bonds contribute to water’s high high specific heatspecific heat (amount of heat needed to raise (amount of heat needed to raise the temperature of 1 gm of a substance 1°C) - the temperature of 1 gm of a substance 1°C) - due to the fact that hydrogen bonds must be due to the fact that hydrogen bonds must be broken to increase the kinetic energy (motion broken to increase the kinetic energy (motion of molecules) and temperature of a substance of molecules) and temperature of a substance --> temperature fluctuation is minimal.--> temperature fluctuation is minimal.

Water has a Water has a high heat of vaporizationhigh heat of vaporization - - large amount of heat is needed to evaporate large amount of heat is needed to evaporate water because hydrogen bonds must be water because hydrogen bonds must be broken to change water from liquid to gaseous broken to change water from liquid to gaseous state.state.

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4. 4. hydrophobic interactionshydrophobic interactions Nonpolar molecules are not soluble in water Nonpolar molecules are not soluble in water

because water molecules interact with each other because water molecules interact with each other rather than nonpolar molecules --> nonpolar rather than nonpolar molecules --> nonpolar molecules are excluded and associate with each molecules are excluded and associate with each other (known as the hydrophobic effect).other (known as the hydrophobic effect).

Nonpolar molecules are hydrophobic.Nonpolar molecules are hydrophobic.

Molecules such as detergents or surfactants are Molecules such as detergents or surfactants are amphipathicamphipathic (have both hydrophilic and (have both hydrophilic and hydrophobic portions to the molecule).hydrophobic portions to the molecule).

All form micelles (spheres in which hydrophilic All form micelles (spheres in which hydrophilic heads are hydrated and hydrophobic tails face heads are hydrated and hydrophobic tails face inwardinward

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5) 5) other noncovalent interactions in other noncovalent interactions in biomoleculesbiomolecules

There are There are four major noncovalent forces four major noncovalent forces involved in the involved in the structure and function of biomolecules:structure and function of biomolecules:

i) i) hydrogen bondshydrogen bondsMore important when they occur between and within More important when they occur between and within

molecules --> stabilize structures such as proteins and molecules --> stabilize structures such as proteins and nucleic acids.nucleic acids.

ii) ii) hydrophobic interactionshydrophobic interactions Very weak.Very weak. Important in protein shape and membrane structure.Important in protein shape and membrane structure.iii) charge-charge interactions or (ionic bonds)iii) charge-charge interactions or (ionic bonds) Occur between two oppositely charged particles.Occur between two oppositely charged particles.

Strongest noncovalent force that occurs over greater Strongest noncovalent force that occurs over greater distances.distances.Can be weakened significantly by water molecules (can Can be weakened significantly by water molecules (can interfere with bonding).interfere with bonding).

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noncovalent interactions (continuation)noncovalent interactions (continuation)

iv)iv) van der Waals forcesvan der Waals forces Occurs between neutral atoms.Occurs between neutral atoms. Can be attractive or repulsive ,depending upon the distance Can be attractive or repulsive ,depending upon the distance

of the two atoms.of the two atoms. Much weaker than hydrogen bonds.Much weaker than hydrogen bonds. The actual distance between atoms is the distance at which The actual distance between atoms is the distance at which

maximal attraction occurs.maximal attraction occurs. Distances vary depending upon individual atoms.Distances vary depending upon individual atoms.

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6)6)Nucleophilic nature of waterNucleophilic nature of water

Chemicals that are electron-rich (Chemicals that are electron-rich (nucleophilesnucleophiles) seek ) seek electron-deficient chemicals (electron-deficient chemicals (electrophileselectrophiles).).

Nucleophiles are negatively charged or have unshared pairs Nucleophiles are negatively charged or have unshared pairs of electrons --> attack electrophiles during substitution or of electrons --> attack electrophiles during substitution or addition reactions.addition reactions.

Examples of nucleophiles: oxygen, nitrogen, sulfur, carbon, Examples of nucleophiles: oxygen, nitrogen, sulfur, carbon, water (weak).water (weak).

Important in condensation reactions, where hydrolysis Important in condensation reactions, where hydrolysis reactions are favored.reactions are favored. e.g. protein ------> amino acidse.g. protein ------> amino acids

In the cell, these reactions actually only occur in the In the cell, these reactions actually only occur in the presence of hydrolases.presence of hydrolases.

Condensation reactions usually use ATP and exclude water Condensation reactions usually use ATP and exclude water to make the reactions more favorable.to make the reactions more favorable.

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7) 7) Ionization of waterIonization of water

Pure water ionizes slightly can act as an acid (proton donor) Pure water ionizes slightly can act as an acid (proton donor) or base (proton acceptor).or base (proton acceptor).

2H2O ---> H3O+ + OH-, but usually written2H2O ---> H3O+ + OH-, but usually written

H2O ---> H+ + OH-H2O ---> H+ + OH- Equilibrium constant for water:Equilibrium constant for water:

Keq = [H+][OH-] Keq = [H+][OH-] At equilibrium, [H+] = [OH-], soAt equilibrium, [H+] = [OH-], so

1.0 x 10-14M2 = [H+]21.0 x 10-14M2 = [H+]2

1.0 x 10-7 = [H+]1.0 x 10-7 = [H+]

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8- 8- pH scalepH scale

pHpH = - log [H+], so at equilibrium= - log [H+], so at equilibrium

pH = -log (1.0 x 10-7) = 7pH = -log (1.0 x 10-7) = 7

pH <7 is acidic, pH > 7 is basic or alkalinepH <7 is acidic, pH > 7 is basic or alkaline

1 change in pH units equals a 10-fold 1 change in pH units equals a 10-fold change in [H+]change in [H+]

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Acid Dissociation Constants of Weak Acid Dissociation Constants of Weak AcidsAcids A strong acid or base is one that completely dissociates in A strong acid or base is one that completely dissociates in

water.water. e.g. HCl ---> H+ + Cl-e.g. HCl ---> H+ + Cl- A weak acid or base is one that does not; some proportion of A weak acid or base is one that does not; some proportion of

the acid or base is dissociated, but the rest is intact.the acid or base is dissociated, but the rest is intact. A weak acid or base can be described by the following A weak acid or base can be described by the following

equation:equation: weak acid (H) ----> H+ + A-weak acid (H) ----> H+ + A- Each acid has a characteristic tendency to lose its proton in Each acid has a characteristic tendency to lose its proton in

solution.solution. The stronger the acid, the greater the tendency to lose that The stronger the acid, the greater the tendency to lose that

proton.proton. The equilibrium constant for this reaction is defined as the The equilibrium constant for this reaction is defined as the

acid dissociation constant or Ka.acid dissociation constant or Ka.Ka = [H+] [conjugate base or A-]Ka = [H+] [conjugate base or A-]

[HA][HA] The pKa is a measure of acid strength. The more strongly The pKa is a measure of acid strength. The more strongly

dissociated the acid, the lower the pKa, the stronger the acid.dissociated the acid, the lower the pKa, the stronger the acid.

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BuffersBuffers

Solutions that prevent changes in pH when bases or acids are Solutions that prevent changes in pH when bases or acids are added.added.

Consist of a weak acid and its conjugate base.Consist of a weak acid and its conjugate base. Work best at + 1 pH unit from pKa --> maximal buffering Work best at + 1 pH unit from pKa --> maximal buffering

capacity.capacity. Excellent example:Excellent example: blood plasma-carbon dioxide- carbonic acid- bicarbonate buffer blood plasma-carbon dioxide- carbonic acid- bicarbonate buffer

systemsystemCO2 + H2O ----> H2CO3 -------> HCO3- + H+CO2 + H2O ----> H2CO3 -------> HCO3- + H+

If [H+] increases (pH falls), momentary increase in If [H+] increases (pH falls), momentary increase in [H2CO3], and equation goes to the left.[H2CO3], and equation goes to the left.

Excess CO2 is expired (increased respiration) to re-establish Excess CO2 is expired (increased respiration) to re-establish equilibrium. equilibrium.

Occurs in hypovolemia, diabetes, and cardiac arrest.Occurs in hypovolemia, diabetes, and cardiac arrest. If [H+] falls (pH increases), H2CO3 will dissociate to release If [H+] falls (pH increases), H2CO3 will dissociate to release

bicarbonate ion and hydrogen ion. This results in a fall in bicarbonate ion and hydrogen ion. This results in a fall in CO2 levels in the blood. As a result, breathing slows.CO2 levels in the blood. As a result, breathing slows.

Occurs in vomiting, hyperventilation (coming at equation Occurs in vomiting, hyperventilation (coming at equation from left).from left).