Structures of Amino Acids - University of Nairobi Personal ... · Amino Acids, Peptides and Proteins Introduction 3:36 PM 4 • These building blocks (a-amino acids) are linked through

Structures of Amino Acids

Amino Acids, Peptides and ProteinsIntroduction

33:36 PM

• Proteins are biopolymers assembled in ribosomes under the

control of nucleic acids from a menu of L-a-amino acids.

• Proteins play important roles in all aspects of cell structure

and function:

• They hold it together, protect and give structure to the body

(structural proteins e.g. muscle, skin, hair).

• As enzymes, hormones and antibodies, they run it (they

catalyse, regulate and protect the body chemistry).

• They are the principal materials of nerves and blood. In the

form of haemoglobin and myoglobin, they transport oxygen

within an organism.

• Of all chemical compounds, proteins must almost certainly

be ranked first, for they are the substances of life.

Amino Acids, Peptides and ProteinsIntroduction

43:36 PM

• These building blocks (a-amino acids) are linked through

amide (peptide) bonds to give macromolecules with

polypeptide backbones and side-chains containing a variety

of simple functionalities based on the amino acids selected.

• The a-amino acids may be considered to polymerize, atleast

conceptually, through the elimination of a water molecule to

form an amide bond (peptide bond)

CH2N

R

COOH

H

CH2N

R'

COOH

H

+ CHN

R

H

C

O

CNH

R'

C

H

Loss of H2O

Amide (Peptide) bond

Amino Acids

Condensation

Polypeptide

n n

O

n

• We will start by looking at the building blocks of proteins to

gain incite of the entire structure and functions of proteins.

Amino AcidsDefinition

53:36 PM

• The physical, chemical and biochemical properties of a

protein or peptide are determined by its constituent a-amino

acids (building blocks).

• It is essential, therefore, to look at the individual amino acids

and their characteristics to get a clue of how they influence

the nature of the peptide or protein which they are

incorporated.

• Amino acids are carboxylic acids that also contain an amino

functional group within their structural framework.

Amino AcidsClassification

6

• Amino acids are classified as a,b,g,d and so on, according to

the relative location of the amino group to the carboxylic acid

moiety on the parent chain of the amino acid.

• Since natural proteins are composed of L-a-amino acids only,

the rest of the discussion will focus on a-amino acids.

a-Amino AcidsDefinition

7

• Although more than 700 different amino acids, of diverse

classifications (a, b, g, and so on), are known to occur

naturally; only a group of 20 a-amino acids, called standard

amino acids, is found in nearly all natural proteins and

commands special attention.

• The use of these 20-amino acids in the biosynthesis of

proteins is governed by the genetic code.

NH2

C

H

COOHR

a-carbon

a-amino group

side chain

NH2

C

H

COOHH

H

COOH

GlycineSimplest amino acid

ProlineSecondary amino group

NH

a-Amino AcidsStructure: Things to Note

8

• There are some common features of these amino acids that

should be noted.

• All, but one of these a-amino acids, contain a primary amino

group and a carboxylic acid group attached to the same

carbon and conform to the general structure above.

• The one exception is proline, which contains a secondary

amino group in which the amino nitrogen is incorporated into

a five-membered ring.

• The simplest a-amino acid is glycine (aminoacetic acid).

• With the exception of glycine, all the other a-amino acids are

chiral.

• The standard amino acids differ from each other only on the

structure of the side chains bonded to their a-carbon atoms.

a-Amino AcidsStructures of Standard Amino Acids

9

• The 20 amino acids can be grouped based on the nature of

the side chain (R).

• The following categories of side chains can be envisaged:

i. The R is hydrogen or an alkyl group

ii. The R contains an alcohol function

iii. The R contains sulphur

iv. The amino group is secondary or part of a ring

v. One hydrogen in alanine is replaced by an aromatic or

heteroaromatic (indole) ring

vi. One amino group and two carbonyl groups

vii. One carbonyl group and two amino groups

Structures of a-Amino AcidsAmino Acids with One Amino Group and One Carbonyl

10

• For simplicity, a system of abbreviated codes is used to refer

to these amino acids. In this system, each amino acid has a

three-letter code, derived from its trivial name.

(a) The R is hydrogen or an alkyl group

Name Abbreviation Structure Isoelectric point

Glycine Gly 6.0

Alanine Ala 6.0

Valine Val 6.0

Leucine Leu 6.0

Isoleucine Ile 6.0

C C

H

NH2

H

O

OH

C C

H

NH2

CH3

O

OH

C C

H

NH2

C

O

OHCH3

CH3

H

C C

H

NH2

CH2

O

OHCH

CH3

CH3

C C

H

NH2

C

O

OHCH3CH2

CH3

H


11

(b) The R contains an alcohol function


Serine Ser 5.7

Threonine Thr 5.6

(c) The R contains sulphur

Cysteine Cys 5.0

Methionine Met 5.7

(d) The amino group is secondary or part of a ring

Proline Pro 6.3

C C

H

NH2 O

OHCH2HO

C C

H

NH2 O

OHCHO

Me

H

C C

H

NH2 O

OHCH2HS

C C

H

NH2

CH2CH2

O

OHSCH3

N COH

OH

H


12


(d) The amino group is secondary or part of a ring

Proline Pro 6.3

(e) One hydrogen in alanine is replaced by an aromatic or heteroaromatic

(indole) ring

Phenylalanine Phe 5.5

Tyrosine Tyr 5.7

Tryptophan Trp 5.9

N COH

OH

H

C C

H

NH2

CH2

O

OH

C C

H

NH2

CH2

O

OH

N

H

Structures of a-Amino AcidsAmino Acids with One Amino Group and Two Carbonyl Groups

13


(f) One amino group and two carbonyl groups

Aspartic acid Asp 2.8

Glutamic acid Glu 3.2

Asparagine Asn 5.4

Glutamine Gln 5.7

C C

H

NH2

CH2

O

OHC

O

HO

C C

H

NH2

CH2CH2

O

OHC

O

HO

C C

H

NH2

CH2CH2

O

OHC

O

H2N

Structures of a-Amino AcidsAmino Acids with Two Amino Groups and One Carbonyl Group

14

(g) One carbonyl group and two amino groups


Lysine Lys 9.7

Arginine Arg 10.8

Histidine His 7.6

C C

H

NH2

CH2CH2CH2

O

OHNHC

H2N

HN

C C

H

NH2

CH2

O

OH

N

N

H

Structures of a-Amino AcidsEssential Amino Acids

15

• While humans posses the capacity to biosynthesize about

half of the amino acids needed to make proteins, they must

obtain certain of the others from their diet.

• Those that must be obtained from dietary sources are called

essential amino acids. They can be present in the diet in the

free form, but most commonly in the combined natural form

as proteins.

Arginine Histidine Isoleucine Leucine Threonine

Lysine Methionine Phenylalanine Tryptophan Valine

The ten essential amino acids

• Any Help In Learning These Little Molecules Proves Truly

Valuable

Mnemonic for the ten essential amino acids

Structures of a-Amino AcidsSources of a-Amino Acids

16

• Proteins are essential to humans, since they are the only

natural source of amino acids that can be used by the body

to build its enzymes, hormones and muscle etc.

• Although the amino acids occur in proteins linked through

peptide bonds, they are hydrolysed into their individual

amino acids using proteases. These individual amino acids

are then combined by the body according to the genetic code

to provide the requisite peptides or proteins.

• Proteins that provide all the essential amino acids in about

the right proportions for human nutrition are called complete

proteins e.g. meat, fish, milk and eggs.

• Proteins that are severely deficient in one or more of the

essential amino acids are called incomplete proteins.

Structures of a-Amino AcidsComplete vs Incomplete Proteins

17

• Animal proteins are usually complete proteins, while plant

proteins are generally incomplete.

Plant Protein Source Proteins Deficient in Amino Acid(s)

Rice Lysine and Threonine

Maize Lysine and Tryptophan

Wheat Lysine

Beans and other legumes Methionine

• Beans, peas and other legumes are the nearest to complete

proteins among the common plants, but they are deficient in

methionine.

• Combining maize and beans is an economical way of making

up for the deficiencies of amino acids inherent in the

individual protein sources.

Structures of a-Amino AcidsChirality of a-Amino Acids

18

• With the exception of glycine, where R = H, the rest of the a-

amino acids have a stereogenic (chiral) centre at the a-

carbon. Consequently, all a-amino acids, except glycine are

chiral and optically active.

• Protein chemists have a long tradition of using the D-L

system of notation to specify the configuration of amino

acids. Indeed, all a-amino acids that are constituents of

natural proteins are of the L-configuration.

• Given the current prevalent use of the R-S system in defining

the configuration of a chiral centre, there is need to relate

this age-old D-L system to the contemporary R-S system.

Chirality of a-Amino AcidsD-L vs R-S Notation for Assigning Stereochemistry

19

• The D-L notation for assigning configurations of a-amino

acids is an extension of the same notation used in assigning

configurations of sugars in carbohydrate chemistry based on

the Fischer projections of the pair of enantiomers of

glyceraldehyde.

C

CHOCH2

HO

HOH

D-(+)-Glyceraldehyde

R-(+)-Glyceraldehyde

C

CHO

HO

H

CH2OH

L-(-)-Glyceraldehyde

S-(-)-Glyceraldehyde

[a] = +8.7o[a] = -8.7o

L-(-)-Glyceraldehyde

CHO

C

CH2OH

HHO

1

2

3

OH group on the Leftfor L-series

Most oxiised carbon

Longest carbon chain

CHO

C

CH2OH

OHH

1

2

3

D-(+)-Glyceraldehyde

OH group on the Rightfor D-series


20

• The stereochemistry of naturally-occurring L-a-amino acids

such as L-serine is directly related to the configuration of L-

glyceraldehyde.


21

• On the basis of this semblance, all the natural L-a-amino

acids, except L-cysteine, are (S)-amino acids, while D-amino

acids, except D-cysteine, are (R)-amino acids.

R S

D L

Relationship between the designation and notation

Cysteine is the exception

• This anomally with cysteine arises out of the fact the Cahn-

Ingold-Prelog sequence rules use the atomic weight to

prioritize substituents on a chiral carbon.

• Whereas on most amino acids the a-substituents are either H

or C and hence of lower priority than O of the carboxylic acid,

in cysteine, it is sulphur, which is of higher priority than O.

Chirality of a-Amino AcidsThings to Note about Stereochemistry of Natural a-Amino

Acids

22

• Although, all the chiral a-amino acids that constitute proteins

have the L-configuration at the a-carbon, it should not be

taken to mean that D-a-amino acids do not occur naturally.

• There are a number of naturally occurring D-a-amino acids

that do play a role in biochemical systems, such as in the

bacterial cell-walls and some antibiotics. D-Alanine and D-

glutamic acid, for example, are constituents of many

bacterial cell walls.

• It is not accidental that bacteria incorporate these D-amino

acids into their cell walls; most of the proteolytic enzymes

that the hosts of these bacteria produce to destroy the

bacteria act only against membranes derived from L-amino

acids. So, integrating D-amino acids into their cell walls

confers a competitive advantage to these bacteria.

Properties of a-Amino AcidsIntroduction

23

• Amino acids combine many of the properties and reactions

of both amines and carboxylic acids.

• The proximity of a basic amino group to an acidic carboxyl

group in the same molecule also results in some unique

properties and reactions.

• The side chains of some amino acids also have functional

groups that lend interesting properties and undergo reactions

of their own.

Documents

Structures of Amino Acids - University of Nairobi Personal ... · Amino Acids, Peptides and Proteins Introduction 3:36 PM 4 • These building blocks (a-amino acids) are linked through