AMINO ACIDS&

PEPTIDES

• In general amino acids are the compounds having at least one acidic group and a basic amino group.

• Amino acids represent building blocks for proteins

Importance of Amino acids

• --- In the formation of proteins

• --- In the formation of compounds of

biochemical importance

• --- In contributing energy to the body

• --- Some amino acids act as neurotransmitters

• Chemical nature of different types of amino acids present in proteins:

• In general, 20 different types of amino acids are present in proteins.

• (In recent years 21st amino acid has been identified, namely Selenocysteine.)

Structure of a typical amino acid,present in proteins

1. Alanine Ala A

2. Arginine Arg R

3. Asparagine Asn N

4. Aspartic acid Asp D

5. Cysteine Cys C

6. Glycine Gly G

7. Glutamine Gln Q

8. Glutamic acid Glu E

9. Histidine His H

10. Isoleucine Ile I

11. Leucine Leu L

12. Lysine Lys K

13. Methionine Met M

14. Phenylalanine Phe F

15. Proline Pro P

16. Serine Ser S

17. Threonine Thr T

18. Tryptophan Trp W

19. Tyrosine Tyr Y

20. Valine Val V

Classification of amino acids, present in Proteins

• Based on Structure;-- Aliphatic, aromatic & heterocyclic

• Based on acid base behavior;-- Acidic, basic & neutral

• Based on polarity;-- Polar & non polar

• Based on the presence of certain groups;-- Sulfur containing, branched chain, hydroxyl

group containing etc.

• Based on metabolic fate;

-- Glucogenic, ketogenic & mixed

• Based on Nutritional significance;

-- Indispensable (essential) &

dispensable (non essential)

Proline is an example for imino acid

Modified amino acids present in proteins

• Examples:

• Hydroxyproline

• Hydroxylysine

• Gamma (γ) carboxyglutamate

Non protein amino acids

• β alanine

• Ornithine

• Citrulline

• Homocysteine

• Homoserine

• Gamma (γ) amino butyric acid

• Taurine

Isomerism in amino acids:

• What is isomerism?

• --- It is the phenomenon by which two or more compounds exhibit same molecular formula but differ in structural pattern

• What are isomers?

• --- These are the compounds that exhibit same molecular formula but differ in structural pattern.

• One of the types of isomerism seen among the organic compounds (including amino acids) is D & L isomerism (Optical isomerism / Enantiomerism / Mirror image isomerism)

• To exhibit such type of isomerism the compound must possess at least one asymmetric carbon atom

• The compound that contains asymmetric carbon atom is said to be optically active

• With the exception of glycine, all the amino acids present in proteins have asymmetric carbon atoms, hence they exhibit optical isomerism

• Based on optical activity, the D and L isomers can be either dextrorotatory (+) or levorotatory (-)

• Example:

• L - Alanine is dextrorotatory (+)

D - Alanine is levorotatory (-)

• All naturally occurring amino acids present in proteins belong to the L category. (However, glycine is without either L or D configuration)

• D amino acids are present in certain bacterial cell wall and in some peptide antibiotics

Acid base behavior of Amino acids

• All the amino acids exhibit acid base behavior

• This feature is by virtue of different ionizable acid/base groups present in amino acids.

• The two common ionizable groups present in all the amino acids are;

--- α- Carboxyl & α- Amino

• Apart from this, certain amino acids contain additional ionizable groups;

• --- Extra Carboxyl groups (β & γ)in

Aspartate & Glutamate, respectively

• --- Extra (ε) amino group in lysine

• --- Guanido (guanidino) group in Arginine

• --- Imidazole group in Histidine.

• Each ionizable group of amino acid can exist in two reversible forms;

• --- Protonated & deprotonated

• Eg. – COOH / COO –

• -- NH3+ / NH2

• H2N – C = NH+2 / H2N– C = NH

NH NH

•

Protonated form of imidazole group of Histidine

• The dissociation behavior of different ionizable groups, present in amino acids,can be expressed in terms of pK values.

• pK is negative log. of dissociation constant, K.

• pK is defined as the pH at which an acid group is half dissociated or in other words, pK is the pH at which both protonated (undissociated) & unprotonated (dissociated) forms of acid group are present at equal concentration.

pK values of different ionizable groups of Amino acids

Ionizable groups pK (Approx.)

α – Carboxyl 2.0

α - Amino 9.5

β - Carboxyl (Aspartate) 3.9

γ - Carboxyl (Glutamate) 4.3

ε - Amino (Lysine) 10.5

Guanido (Arginine) 12.5

Imidazole (Histidine) 6.1

• Based on the pK values it is obvious that among different dissociable groups of amino acids, carboxyl group dissociates earlier and guanidino (guanido) group of arginine dissociates much later.

• Since the pK of all the carboxyl groups are much below pH 7.0, and since these carboxyl groups are in dissociated states at neutral pH, they are considered as acidic groups.

• On the other hand, pK values of α - amino groups, ε-amino group of lysine andguanido group of arginine are much higher than 7.0. Moreover, these groups exist in fully associated (protonated) form at neutral pH. Hence these groups are called as basic groups.

Henderson-Hasselbalch equation:

This is the equation that depicts relationship among, pK, pH and concentration of acid and its conjugate base

pH = pKa + logConjugate base

Acid

• Dissociation pattern of different types of Amino acids:

• Amino acids exist in different ionic forms at different pH.

• At low pH they are in fully protonated(undissociated) form

• At high pH they are in fully deprotonated(dissociated) form

• If the ionic form of an amino acid contains equal number of +ve and –ve charges, it is called as zwitterionic form.

• The pH at which an amino acid exists in zwitterionic form is called as isoelectric pH (pI)

• Each amino acid has an pI value.

• pI value indicates whether an given amino acid is acidic, neutral or basic.

IONIC SPECIES OF NEUTRAL AMINO ACIDS

Zwitterionic

structure

Cationic

structure

Anionic

structure

IONIC SPECIES OF ASPARTATE

IONIC SPECIES OF HISTIDINE

• Work out the ionic species of Lysine

• Buffering action of Amino acids:

Solutions of weak acids and their conjugate bases exhibit the ability to resist pH change when strong acids or bases are added. They are called buffers.

All the acid/base groups of amino acids can exhibit buffering action

• Buffering action is maximum at pK values

• Good buffering action is also observed at pH 1.0 unit above and below the pK value.

• At physiological pH of body fluids, only imidazole group of histidine can act as buffer.

• Why ?

PEPTIDESAND

POLYPEPTIDES

• Formation of Peptide bonds:

• A peptide bond is formed when an amino group of one amino acid reacts with a carboxyl group of another amino acid.

Dipeptide

Two amino acids linked by a peptide linkage forms a dipeptide

Ex.

Alanyl-glycine

Glycyl-cysteine

Tripeptide

Three amino acids linked by 2 peptide bonds form a tripeptide

glu-cys-glycine

Ala-val-phe

Conventionally amino terminal amino acid is written on the left…..last

one containing free carboxyl group at the right

Peptides with few amino acids , eg. 2-10 are generally termed as oligopeptides.

Generally polymers containing more than 10 amino acids are called polypeptides.

Polypeptides containing many amino acids and having higher structural complexity are called as proteins.

• Peptide bond is rigid and planar.

• It has partial double bond character.

• No freedom of rotation around the peptide bond

• Exists in trans form.

Short Peptides of Biological Importance

1.Dipeptides:

Carnosine: β-alanyl histidine

Anserine: It is N-methyl carnosine

These two peptides are found in muscle.

They activate myosin ATPase activity.

Both are capable of chelating copper and

enhance copper uptake.

Glutathione:

It is a tripeptide consisting of glutamate, cysteine & glycine

(Gamma glutamyl cysteinyl glycine).

It is conventionally written as GSH

CH2

CH2

H-C-NH3+

COO -

O

C

N

H

SH

CH2

CH

C

O

H

N

CH2

COO -

Glutamyl cysteinyl glycine

It is an important component of cellular antioxidant defense system.

It is an essential component, required for integrity of RBC membrane.

It participates as cofactor in many reactions.

2 molecules of GSH can donate a pair hydrogen to reduce a substrate

H2O2 + 2 GSH 2H2O + GS-SG

glutathione peroxidase

GS-SG 2 GSH

NADPH + H+ NADP+

Glutathione reductase

Thyrotropin Releasing Hormone (TRH) :

It is a tripeptide (PyroGlu-His-Prolinamide).

Secreted by hypothalamus. It stimulates release of

Thyroid stimulating hormone (TSH) from anterior

pituitary gland.

Enkephalin:

It is a pentapeptide (made up of 5 amino acids)found in brain.

It inhibits sense of pain

Angiotensin II

A peptide with 8 amino acids

It is a hypertensive agent

It stimulates release of aldosterone from adrenal cortex.

Vasopressin ( antidiuretic hormone or ADH):

Contains 9 amino acids. Secreted by posterior pituitary gland. It regulates water excretion by kidney. ADH deficiency is associated with diabetes insipidus

Oxytocin:

It is also made up of 9 amino acids. Secreted by posterior pituitary gland.

Causes contraction of uterus.

Used in induction of labor

• Aspartame:

• A synthetic dipeptide made up of aspartate & methyl ester of phenylalanine

• Artificial sweetner (200 times sweeter than sucrose)

Polypeptides of Biological Significance:

Insulin

Glucagon

ACTH

Gastrin

• Insulin:

• Insulin is a polypeptide hormone produced in pancreas by β-cells of islets of Langerhans.

• Contains 51 amino acids

• Consists of two chains; A and B chain linked by two inter-chain disulfide bonds.

• In addition, there is an intra chain disulfide bond

• Major action: To decrease blood glucose level

• Glucagon:

• It is a polypeptide hormone with 29 amino acids. It is secreted by α cells of islets of Langerhans.

• Major action: Hyperglycemic & Lipolytic