Amino Acids & Chemical Evolution of Proteins

Amino Acids

Introduction

• Amino Acids of Proteins

a. General Properties

b. Peptide Bonds

c. Classification & Characterization

d. Acid – Base Properties

e. A Few Words on Nomenclature

Introduction, Cont.

• Optical Activity

a. An Operational Classification

b. The Fisher Convention

c. The Cahn – Ingold – Prelog System

d. Chirality and Biochemistry

Introduction, Cont.

• Nonstandard Amino Acids

a. Amino Acid Derivatives in Proteins

b. Specialized Roles of Amino Acids

Introduction, Cont.

• Chemical Evolution

a. Sickle Cell Anemia: The Influence of

Natural Selection

b. Species Variation in Homologous

Proteins: The Effect of Neutral Drift

c. Evolution Through Gene Duplication

Amino Acids of Proteins General Properties

• pK Values of the 20 Standard

- pK1 refer to the α – Carboxylic Acid

- pK2 refer to the α – Amino Groups

- pKR refer to the Side Groups with Acid-Base

Properties

What is pK ?!

Amino Acids of Proteins General Properties, Cont.

• In chemistry and Biochemistry, a

Dissociation Constant or an Ionization

Constant is a Specific Type of Equilibrium

Constant Used for Reversible Reactions or

Processes

The pK Value is Defined as:

pK = - log Kd

Amino Acids of Proteins General Properties, Cont.

• α – Carboxylic Acid Groups lie in small

range 2.2

• Above pH 3.5 These Groups are almost

Entirely in Their Carboxylate Forms

• α – Amino Groups All Have pK Values

Near 9.4

• Below pH 8.0 These Groups are almost

Entirely in Their Ammonium Ion Forms

Amino Acids of Proteins General Properties, Cont

In the physiological pH Range, Both

the Carboxylic Acid and the Amino

Groups of α – Amino Acids are

Completely Ionized


The Amino Acids Plays a Role as a Buffer


• Substances with this Property are Said to

be “Amphoteric” or “Ampholytes”

What Do we Mean By Amphoteric

Substances?!


• Amphoteric Substances are any Substance

reacting as acid and base: able to react

chemically as either an acid or a base

• The Zwitterionic Character of the α – Amino

Acids Has Been Established by Several

Methods

- Spectroscopic Measurements

- X-Ray Crystal Structure Determinations


• The Physical Properties of Amino Acids are Characteristic of Ionic Compounds

• Most α – Amino Acids Have Melting Points Nearby 300˚C

• Nonionic Amino Acids Derivatives Usually Melt Around 100˚C

• More Soluble in Polar Solvents

• Most α – Amino Acids are Very Soluble in Water

Amino Acids of Proteins


b. Peptide Bonds





Peptide Bonds

• α – Amino Acids Polymerize Through the

Elimination of Water Molecule


Peptide Bonds, Cont

• The Resulting CO – NH Linkage Is Known

as a Peptide Bond


Peptide Bonds, Cont

• 2 A.A. = Dipeptide

• 3 A.A. = Tripeptide

• 3 < A.A. < 10 = Oligopeptide

• A.A. > 10 = Polypeptide

Proteins are Molecule that Consist of One or

More Polypeptide Chains


Peptide Bonds, Cont

• Polypeptides Range in Length from ~ 40 to

Over 4000 A.A. Residue

• The Average Mass of an A.A. is ~ 110 D

• Therefore the molecular Masses of

Polypeptides Range From ~ 4 to over 440

KD

• Polypeptides are Linear Polymers


Peptide Bonds, Cont

• Huge Number of Different Protein

Molecules Can Exist

• For Example: A Small Protein Molecule

Consists of a Single Polypeptide Chain of

100 Residue of A.A. Can Form 20100

Possible Unique Polypeptide Chain of This

Length


Peptide Bonds, Cont

The Various organisms on Earth

Collectively Synthesize an Enormous

Number of Different Protein

Molecules whose Great Range of

Physicochemical Characteristics Stem

Largely from the Varied Properties of

the 20 “Standard” Amino Acids



b. Peptide Bonds





Classification & Characterization

• The Polarity of A.A’s. Side Chain (R Groups)

is the Most Useful Way to Classify the 20

Standard A.A.

• Proteins Fold in Response to Tendency

to Remove Their Hydrophobic Side Chain

from Contact with Water and to Solvate

Hydrophilic Side Chain

• According to that Classification Scheme,

there are Three Major Types of A.A.


Classification & Characterization, Cont

1- Nonpolar A.A. Side Chains

• Glycine: Was the First A.A. to be Identified

& has the Smallest Possible Side Chain, an

H Atom.



• Alanine, Valine, Leucine & Isoleucine:

Have Aliphatic Hydrocarbon Side Chains



• Methionine: Has a a Thiol Ether Side

Chain

• Proline: A Cyclic Secondary A.A. has

Conformational Constraints Imposed by

the Cyclic nature of it’s Pyrrolidine Side

Group



• Phenylalanine: With it’s Phenyl Moiety,

Contain Aromatic Side Group Which is

Characterized as Nonpolar Group



• Tryptophan: With it’s Indole Group,

Contain Aromatic Side Group Which is

Characterized as Nonpolar Group



2- Uncharged Polar A.A. Side Chains

• Serine & Threonine: Bear Hydroxylic R

Group of Different Sizes



• Asparagine & Glutamine: Have Amide-

Bearing Side Chains of Different Sizes



• Tyrosine: Has a Phenolic Group, which,

together with Aromatic Groups of

Phenylalanine & Tryptophan Accounts for

Most of the UV Absorbance and

Fluorescence Exhibited by Proteins



• Cysteine: Has a Thiol Group Which is

Make Disulfide Bond with other Cysteine

Molecule, it means that it can Join

Separate Polypeptide Chains or Cross-Link

Two Cysteine in the Same Chain



3- Charged (Positively) Polar A.A. Side Chains

• Lysine: Has a Butylammonium Side Chain

• Arginine: Has Guanidino Group



• Histidine: Which Carry Imidazolium Moiety

• Only Histidine with pkR

= 6.0 Ionizes within the Physiological pH

• As a Consequence, Histidine Side Chain often Participate in the Catalytic Reaction of Enzyme



3- Charged (Negatively ) Polar A.A. Side

Chains

• Aspartic Acid & Glutamic Acid: Are

Negatively Charged above pH = 3.0



b. Peptide Bonds





Acid – Base Properties



b. Peptide Bonds





A Few Words on Nomenclature

• The Three Letter Abbreviation

• Widely Used Throughout Biochemical Literature

• The One Letter Symbol

• Often Used when Comparing the A.A. Sequences of Several Similar Proteins

• A.A. in Polypeptides are Named by Dropping the Suffix -ine and Replacing it by -yl

• For example: Alanine Alanyl



b. Peptide Bonds




Optical Activity





Optical Activity

• All A.A. - Except (Gly) - are Optically Active

• Optically Active Molecules Have an

Asymmetry Such that they are not

Superimposable on their mirror Image

• The Central Atom is Known as Chiral Center

• Molecules that are Nonsupeimposable Mirror

Image are Known as Enantiomers

Optical Activity

An Operational Classification

• Molecules are Classified as Dextrorotary (Greek: Dextro, right) or Levorotary (Greek: Levo, left)

• This Can be Determined by an Instrument Known as a Polarimeter

• The Quantitative measure of the Optical Activity of the Molecule is Known as it’s Specific Rotation

Observed Rotation

[α]25

=

D

Optical Path Length (dm) X Concentartion (gf. Cm-3

)

Optical Activity





Optical Activity

The Fisher Convention

• The Configuration of the Groups About an

Asymmetric Center is related to that of

Glyceraldehyde

Optical Activity

The Fisher Convention

• Fischer Projections are Abbreviated Structural Forms that Allow One to Convey Valuable Stereochemical Information to a Chemist without them Having to Draw a 3D Structural Representation of a Molecule

• Horizontal Lines Represent Bonds Coming Out of the Plane of the Paper and Vertical Lines Represent Bonds Going Behind the Plane of the Paper.

Optical Activity





Optical Activity

The Cahn – Ingold – Prelog System

• Fischer Scheme is Awkward for Molecules with More than One Asymmetric Center

• The Four Groups Surrounding a Chiral Center are Ranked According to a Specific Scheme:

Atoms of Higher Atomic Number Bonded

to a Chiral Center are Ranked Above

those of Lower Atomic Number

Optical Activity


• For Example: the Oxygen of OH Group

Takes Precedence Over the Carbon Atom

of a CH3 Group that is Bonded to the Same

Chiral Center

• The Order of Priority of Some Common

Functional Groups is:

SH > OH > NH2 > COOH > CHO > CH2OH > C6H5 > CH3 > 2H > 1H

Optical Activity


• The Prioritized Groups are Assigned the Letters : W, X, Y, Z

• The Order of Priority Rating is:

W > X > Y > Z

• If the Order of the Groups W X Y is Clockwise, then the Configuration of Asymmetric Center is Designated (S)

• If the Order of the Groups W X Y is Counterclockwise, then the Configuration of Asymmetric Center is Designated (R)

Optical Activity





Optical Activity

Chirality and Biochemistry

• The Biosynthesis of a Substance

Possessing Asymmetric Centers Almost

Invariably Produces a Pure Stereoisomer

• The L Configuration of A.A. is One Example

of this Phenomenon

Optical Activity





Nonstandard Amino Acids




• The 20 Common A.A. are the Only A.A.

that Occur in Biological Systems

• Nonstandard A.A. Residue are Often

Important Constituents of Proteins and

Biologically Active Polypeptides

• Many A.A., However, are not Constituents

of Proteins


Amino Acid Derivatives in Proteins

• In All Known Cases But One (Section 30-2D-P: 923), However, These Unusual A.A. Result From The Specific Modification of an A.A. Residue After the Polypeptide Chain Has Been Synthesized

• Famous Modified A.A.:

4 - hydroxyproline

5 - hydroxyproline

• Important Structural Constituents of the Fibrous Protein Collagen

Nonstandard Amino Acids. Specialized Roles of Amino Acids

• Nature Tends to Adapt Materials and

Processes that are Already Present to a New

Functions

• Chemical Messenger Between Cells

Neurotransmitters:

Glycine

GABA = Glutamate Decarboxylation Product)

Dopamine = ( Tyrosine Product)

Nonstandard Amino Acids. Specialized Roles of Amino Acids

Mediator of Allergic Reaction:

Histamine (Histidine Decarboxylation Product)

Hormone:

Thyroxin

Important Intermediates in Metabolic Pathways:

Ornithine

Homocysteine

S - Adenosylmethionine

Amino Acids & Chemical Evolution of Proteins

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