Amino Acid, Peptides (biomedical importance)

BIOCHEMISTRY JSMU

16-11-2013

ANATOMY OF AN AMINO ACID

Non-polar amino acids (Revisit)

Polar, non-charged amino acids

Negatively-charged amino acids

Positively-charged amino acids

Nomenclature

C

R

H

COOHH2Nα

1. FUNCTIONS OF AMINO ACIDSAmino Acid (AA) - Protein

Peptides (from the Greek, "digestible"), are formed through condensation of amino acids through peptide bonds.

: basic unit

: amino acid chain, containing 2 or more AA.

: containing < 100 AA.

: > 100 AA.

Peptide bond: a chemical bond formed between two AA

- the of one amino acid reacts with

- the of the other amino acid,

- releasing a molecule of .

This is a condensation (dehydration) reaction.

A peptide bond (amide bond) Covalent chemical bond formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, causing the release of a molecule of water (H2O), hence the process is a dehydration synthesis reaction (also known as a condensation reaction), and usually occurs between amino acids. The resulting C(O)NH bond is called a peptide bond, and the resulting molecule is an amide.

It is the partial double-bond character of the peptide bond that defines the conformations a polypeptide chain may assume.

It is shorter then a single bondRigid & planar

The group can take one of two major configurations:

Cis or Trans

CIS CONFIG

TRANS CONFIG

Peptide Nomenclature:

Direction of codons and amino acidsLanguage: meaningTwo ends (Amino and Carboxylic)How to name

ANGIOTENSIN-II Asp-Arg-Val-Tyr-Ile-His-Pro-Phe

FUNCTIONS OF AMINO ACIDS

Glycine (sweet)

Heme synthesisPurine synthesis

Glutathione synthesisConjugation with bile acidsDetoxification: e.g., benzoic acid

Inhibitory neurotransmitter

Methionine

S~adenosyl methionine Contributes for spermine & spermidine

synthesis(polyamines)

Cell proliferation & growthMethyl group donor

Remaining carbon converts to succinyl CoA

Cysteine:Component of Coenzyme APrecursor of Taurine

Histidine: Decarboxylation gives HISTIMINE

Arginine:Nitric oxide ( NO )

Arginine phosphateCreatine phosphateCreatinine

Tryptophan Serotonin

A potent vasoconstrictorStimulator of smooth muscle contraction

Anti depressant

Tyrosine: Thyroid hormone

Noradrenaline Adrenaline

Melatonin

Non-Standard amino acids

• 4-Hydroxyproline, a derivative of proline, • 5- Hydroxylysine, derived from lysine.

Collegen • Methyl-lysine Myosin• Carboxyglutamate- Prothrombin• Desmosine- Elastin• Selenocysteine- active site for

enzymes• Ornithine & Citrulline – urea & arginine

synthesis

• Homocysteine• GABA-(γ-amino-butyric acid)• DOPA• Iodinated amino acids• Pantothenic acid• Argininosuccinic acid• β-alanine

Use of Amino AcidsAspartame: Artificial sweetener (aspartyl-phenylalanine-1-methyl ester).

5-HTP: has been used to treat neurological problems with PKU (Phenylketonuria) &Depression. (5-hydroxytryptophan)

L-DOPA: is a drug used to treat Parkinsonism. (L-dihydroxyphenylalanine)

Monosodium glutamate: is a food additive to enhance flavor.

Peptides • Cytochrome-C• Hemoglobin • Myoglobin • Ribonucleases A• Apolipoprotein B• RNA Polymerases

Non- standard amino acids:

These are either synthesized in the cells or the derivatives of standard AA.

Hydroxy LysineHydroxy Proline

Present in collagen, a fibrous protein of connective tissues.

Methyl lysine: Present in myosine

Gamma carboxyglutamate: Present in Ca++ binding proteins

Ornithine Citrulline Precursor of arginine, urea, spermine & spermidine

Desmosine: Formed by the condensation of FOUR Lysineresidues.

Present in Elastin, a fibrous protein.

Nor epinephrine,

Epinephrine,

Thyroxin (T4)

Triiodothyronine (T3)

Small Peptides:

Aspartam: Artificial sweetner. A dipeptide: Aspartyl-phenylalanyl methyl ester.

Oxytocin: Contains 9 AA.A posterior pituitary hormonecausing uterine contraction.

Bradykinin Contains 9 AA.Inhibitor of inflammation

Glutathione

Detoxification of xenobiotics, H2O2. Intracellular reductant

Transport of AA across the cell membrane.

A tripeptide

Thyrotropin Releasing Factor ( TRF ):

Contains 3 AA.Synthesized in hypothalamusStimulates anterior pituitary For Thyrotropin secretion.

Glucagon:

Contains 29 AAHyperglycemic factor

ACTH: 29 AA, acts on adrenal cortex for cortisol secretion

Neuropeptides:

3. FUNCTIONS OF AMINO ACIDSzwitterion & buffering

Zwitter Ion:At physiological PH (7.4)

• COOH group (weak acid/proton donor) is dissociated forming a negatively charged carboxylate ion (COO-)

• amino group (weak base/proton acceptor) is protonated forming positively charged ion (NH3+) forming.

 The molecule attains both +ve and –ve charges with NO NET chargeA zwitterion can act as either an acid (proton donor) or a base (proton acceptor)

zwitterion & buffering

Partial double bond character of peptide bond:

CN

O

H

N

O

H

This character of peptide bond restrict its free rotation

CN

CC

NC

CN

Polypeptide backbone

CN

CC

NC

CN

α α

α α

O

O

ORH

H

RH

H

H

CN

CC

NC

CN

α α

O

O

ORH

H

RH

H

H

It has three covalent bonds:

Co → NPeptide bond

(No free rotation)Cα→ N Cα→ Co

Free rotationphi angle

─ 57psi angle

─ 47

PROTEIN STRUCTURE

There are FOUR levels of protein structure:

PRIMARY STRUCTURE

SECONDARY STRUCTURE

TERTIARY STRUCTURE

QUATERNAEY STRUCTURE

PRIMARY STRUCTURE

It is the sequence of the amino acid in a protein molecule

It is according to the genetic codes, present in genefor a particular protein.

SECONDARY STRUCTURE

The folding of short contiguous segments( 3 – 30 residues ) of a polypeptide into a geometrically ordered units.

Two types:

1. α- Helix

2. β- Pleated sheet

The polypeptide back bone is twisted by an equalamount about each α- carbon

1. α- Helix

In one complete turn there are 3.6 amino acidswith a pitch of 0.54 nm

The R-groups face outward

0.54 nm3.6 AA

The α- helix is stabilized by :

1. Hydrogen bonds formed between C=O and NH of each fourth residue.

1 – 2 – 3 – 4 – 5 – 6 – 7 – 8 – 9 – 10 – 11 -----

=O =O =O =O =O =O =O =O =O =O

NH

NH

NH

NH

NH

NH

NH

NH

NH

NH

α- helix is also stabilized by the van-der Waalinteractions among the different groups.

The proline and glycine interfere the α- helixeither by giving a turn or bend.

In α- helix, the hydrophobic R-groups acquire theinterior while the hydrophilic R-groups acquire theexterior.

2. β- Pleated Sheet:

Occurs in proteins contain several segments or chains

The amino acids form a zigzag pattern.

The polypeptide backbone is highly extended.

The structure is stabilized by H-bonds formed betweenthe C=O and NH groups of adjacent segments andchains.

Two Types:a) Parallel:

b) Antiparallel:

Tertiary structure:Entire three dimensional conformation of a polypeptidechain indicating how helices, sheets, bends turns andloops assemble to form DOMAIN and how different domains interact with each other in space.

The tertiary structure protein is also called NATIVE protein.

Structure is stabilized by:H- bonds and salt bridges between COOH of Asp and Gluand NH2 group of Arg, Lys and His.

Hydrophobic interaction among the hydrophobic R- groups which acquire the interior.

Quaternary structure:

Proteins having more than one polypeptide chainsacquire quaternary structure.

H- bonds, salt bridges and hydrophobic interactionStabilize the structure.