AMINO ACIDS- OVERVIEW

The general structure of an amino acid molecule, with the amine group on the left and the carboxylic acid group on the right. The R group is dependent on the amino acid.

In chemistry, an amino acid is any molucule that contains both amine and carboxylic acid functional groups. In biochemistry, this shorter and more general term is frequently used to refer to alpha amino acids: those amino acids in which the amino and carboxylate functionalities are attached to the same carbon, the so-called α–carbon.

An amino acid residue is what is left of an amino acid once a molecule of water has been lost (an H+ from the nitrogenous side and an OH- from the carboxylic side) in the formation of a peptide bond.

OVERVIEW cont.

Amino acids are the basic structural building units of proteins. They form short polymer chains called peptides or polypeptides which in turn form structures called proteins. The process of such formation from an mRNA template is known as translation, which is part of protein synthesis.

Phenylalanine is one of the standard amino acids.

OVERVIEW cont.

Twenty amino acids are encoded by the standard genetic code and are called proteinogenic or standard amino acids. Combinations of these amino acids produce every single essential protein for the homeostasis of the human body. At least two others are also coded by DNA in a non-standard manner as follows:

Selenocysteine is incorporated into some proteins at a UGA codon, which is normally a stop codon.

Pyrrolysine is used by some methanogens in enzymes that they use to produce methane. It is coded for similarly to selenocysteine but with the codon UAG instead.

OVERVIEW cont.

Other amino acids contained in proteins are usually formed by post-translational modification, which is modification after translation in protein synthesis. These modifications are often essential for the function of the protein.

Proline is the only proteinogenic amino acid whose side group cyclizes onto the backbone: it links to the α-amino group, and thus is also the only proteinogenic amino acid containing a secondary amine at this position. Proline has sometimes been termed an imino acid, but this is not correct by current nomenclature rules.

OVERVIEW cont.

• Over one hundred amino acids have been found in nature. Some of these have been detected in meteorites, especially in a type known as carbonaceous chondrites.

• Microorganisms and plants can produce uncommon amino acids, which can be found in peptidic antibiotics (e.g., nisin or alamethicin). Lanthionine is a sulfide-bridged alanine dimer which is found together with unsaturated amino acids in lantibiotics (antibiotic peptides of microbial origin).

• Aminocyclopropane-1-carboxylic acid (ACC) is a small disubstituted cyclic amino acid and a key intermediate in the production of the plant hormone ethylene.

OVERVIEW cont.

In addition to protein synthesis, amino acids have other biologically-important roles. Glycine and glutamate are neurotransmitters as well as standard amino acids in proteins. Many amino acids are used to synthesize other molecules, for example:

Tryptophan is a precursor of the neurotransmitter serotonin.

Glycine is one of the reactants in the synthesis of porphyrins such as heme.

Arginine is used to synthesize the hormone nitric oxide.

Numerous non-standard amino acids are also biologically-important: Gamma-aminobutyric acid is another neurotransmitter, carnitine is used in lipid transport within a cell, ornithine, citrulline, homocysteine, hydroxyproline, hydroxylysine, and sarcosine.

OVERVIEW cont.

Some of the 20 standard amino acids are called essential amino acids because they cannot be synthesized by the body from other compounds through chemical reactions, but instead must be taken in with food. In humans, the essential amino acids are lysine, leucine, isoleucine, methionine, phenylalanine, threonine, tryptophan, valine. Histidine and arginine are generally considered essential only in children, because of their inability to synthesise them given their undeveloped metabolisms.

The phrase "branched-chain amino acids" is sometimes used to refer to the aliphatic amino acids: leucine, isoleucine and valine.

GENERAL STRUCTURE

The general structure of proteinogenic alpha amino acids is:

R | H2N-----C----COOH

| H

Structure cont.

Where R represents a side chain specific to each amino acid. Amino acids are usually classified by the properties of the side chain into four groups. The side chain can make them behave like a weak acid, a weak base, a hydrophile, if they are polar, and hydrophobe if they are nonpolar.

ISOMERISM

Most amino acids occur in two possible optical isomers, called D and L. The L amino acids represent the vast majority of amino acids found in proteins.

D amino acids are found in some proteins produced by exotic sea-dwelling organisms, such as cone snails. They are also abundant components of the proteoglycan cell walls of bacteria.

The D-isomer of aspartic acid is found in some proteins as the result of a spontaneous post-translational modification associated with protein aging or as the by-product of enzymatic modification catalyzed by protein L-isoaspartyl methyltransferase.

Sterochemistry

All amino acids (except glycine) recovered from polypeptides are optically active and direction of angle of rotation is measured by polarimeter.

Optically active molecules are asymmetric and the central atoms (C-alpha atoms of amino acids) in such molecules are chiral centers with property of chirality.

These asymmetric centers give rise to enantiomers (nonsuperimposable mirror images of one another) or are stereoisomers (chiral molecules with different configurations about at least one of their asymmetric centers but which are otherwise identical).

Life is based on chiral molecules as biosynthetic processes almost invariably produce pure stereoisomers.

Isomerism cont.

The L and D conventions for amino acid do not refer to their own optical activity, but rather to the optical activity of glyceraldehyde as an analogue of the amino acids.

In the RS system or Cahn-Ingold-Prelog, S-glyceraldehyde is levorotary, and R-glyceraldehyde is dexterorotary, and so S- amino acids are called "L-" even if they are not levorotary, and R- amino acids are likewise called "D-" even if they are not dexterorotary.

Isomerism cont.

Two exceptions exist: In glycine, where R = H, and there is no

isomerism, because two groups on the central carbon atom are identical

In cysteine, the L-S and D-R assignment is reversed to L-R and D-S. Cysteine is structured similarly (with respect to glyceraldehyde) to the other amino acids but the sulfur atom alters the interpretation of the Cahn Ingold Prelog rules.

PEPTIDE BONDING

Proteins are created by polymerization of amino acids. This condensation reaction yields the newly formed peptide bond and a molecule of water.

FORMATION OF PEPTIDE BONDINGFig. 1 alpha amino acidFig. 2 zwitterion structureFig. 3 Two amino acids forming a peptide bond

ARBITRARY CLASSIFICATION OF THE 20 STANDARD AMINO ACIDS

Amino acids are classified by their polarities of their side chains. There are 3 major type of amino acids:I. THE NON POLAR R GROUP II. UNCHARGED POLAR SIDE CHAINS III. CHARGED POLAR SIDE CHAINS

Non-polar, aliphatic, R groups – 9 acids :Glycine (Gly/G)Alanine (Ala/A)Valine (Val/V)Leucine (Leu/LIsoleucine (Ile/I)These have aliphatic hydrocarbon side chains ranging in size from a methyl group for alanine to isomeric butyl groups for L and I.

Non-polar R groups cont.

Methionine (Met/M) – has thioether side chain resembling n-butyl group in physical properties.

Proline (Pro/P) – has a cyclic pyrrolidine side group.

Phenylalanine (Phe/F) – has phenyl moiety)- non-polar aromatic side group

Tryptophan (Trp/W) – has indole non-polar aromatic side group

Non-polar amino acid side chains: Gly, Ala, Val, Leu, Ile, Met, Pro, Phe, Trp

6 Amino acids with uncharged polar side chains

Serine and threonine bear hydroxylic R groups of different sizes.

Asparagine and glutamine have amide-bearing side chains of different sizes.

Tryosine has a phenolic group and is aromatic.

Cysteine has a thiol group and can form a disulfide bond with another cysteine.

Serine (Ser/S), Threonine (Thr/T), Asparagine (Asp/N), Glutamine (Gln/Q), Tyrosine (Try/Y), Cysteine (Cys/C)

5 Amino acids with charged polar side chains, + or -

The side chains of basic amino acids are positively charged at physiological pH values:Lysine – has butylammonium side chainArginine – bears a guanidino groupHistidine – carries a imidazolium moeity

The side chains of aspartic acid and glutamic acid are negatively charged above pH 3.

Amino acids with charged side chains: Lysine (Lys/K), Arginine (Arg/R), Histidine (His/H), Aspartic acid (Asp/D), & Glutamic acid (Glu/E)

AMINO ACID DERIVATIVES

SIDE CHAIN MODIFICATIONS The ‘universal’ genetic code specifies only the 20

essential amino acids. Other amino acids are components of certain proteins

resulting from the specific modification of an amino acid residue after the polypeptide chain has been synthesized.

These modifications include the simple addition of small chemical groups to certain amino acid chains: hydroxylation, methylation, acetylation, and phosphorylation.

Larger groups, including lipids and carbohydrate polymers, are attached to particular amino acid residues of certain proteins

Examples: o- phosphoserine, alpha-carboxyglutamate, 4-hydroxyprolone, 3-methyhistidine

BIOLOGICALLY ACTIVE AMINO ACIDS

The 20 standard amino acids undergo a bewildering number of chemical transformations to other amino acids and related compounds as part of their normal cellular synthesis and degradation.

Many organisms use certain amino acids to transport nitrogen in the form of amino groups.

Amino acids may also be oxidized as metabolic fuels to provide energy.

Amino acids often function as chemical messengers for communication between cells.

Alpha-aminobutric acid and dopamine are neuro transmitters.

Histamine is a mediator of allergic reactions. Thyroxine stimulates vertebrate metabolism. Many peptides (e.g. glutathione) have physiological

functions as hormones or regulatory molecules.