Amino Acids

Amino acids are a biochemical building block. They form long chemical chains called proteins, and shorter chains called peptides. In chemistry, an amino acid is any molecule that contains both amino 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.

Twenty amino acids are encoded by the standard genetic code and are called proteinogenic. Proline is the only cyclic proteinogenic amino acid. Other amino acids contained in proteins are usually formed by modification after translation (protein synthesis). These modifications are often essential for the function of the protein. At least two amino acids other than the standard 20 are sometimes incorporated into proteins during translation:

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.

Over 500 amino acids have been found in nature. Some of them have also been found in meteoritic material. Microorganisms and plants often produce very uncommon amino acids, which can be found in peptidic antibiotics (for example nisin or alamethicin). Lanthionine is a sulfide bridged alanine dimer which is found together with unsaturated amino acids in lantibiotics (antibiotic peptides from microbial origin). 1-Aminocycloproane-1-carboxylic acid ACC is a small disubstituted cyclic amino acid and a key intermediate in the production of the herbal hormone ethylene.

In addition to amino acids for protein synthesis, there are other biologically important amino acids, such as the neurotransmitter GABA, carnitine (used in lipid transport within a cell), ornithine, citrulline, homocysteine, hydroxyproline, hydroxylysine, and sarcosine.

All peptides and polypeptides are polymers of alpha-amino acids. There are 20 a-amino acids that are relevant to the make-up of mammalian proteins. Several other amino acids are found in the body free or in combined states (i.e. not associated with peptides or proteins). These non-protein associated amino acids perform specialized functions. Several of the amino acids found in proteins also serve functions distinct from the formation of peptides and proteins, e.g., tyrosine in the formation of thyroid hormones or glutamate acting as a neurotransmitter.

The a-amino acids in peptides and proteins (excluding proline) consist of a carboxylic acid (-COOH) and an amino (-NH2) functional group attached to the same tetrahedral carbon atom. This carbon is the a-carbon. Distinct R-groups, that distinguish one amino acid from another, also are attached to the alpha-carbon (except in the case of glycine where the R-group is hydrogen). The fourth substitution on the tetrahedral a-carbon of amino acids is hydrogen.

Each of the 20 a-amino acids found in proteins can be distinguished by the R-group substitution on the a-carbon atom. There are two broad classes of amino acids based upon whether the R-group is hydrophobic or hydrophilic. The hydrophobic amino acids tend to repel the aqueous environment and, therefore, reside predominantly in the interior of proteins. This class of amino acids does not ionize nor participate in the formation of H-bonds. The hydrophilic amino acids tend to interact with the aqeuous environment, are often involved in the formation of H-bonds and are predominantly found on the exterior surfaces proteins or in the reactive centers of enzymes.

Hydrolysis of proteins by boiling aqueous acid or base yields an assortment of small molecules identified as a-aminocarboxylic acids. More than twenty such components have been isolated, and the most common of these are listed in the following table. Those amino acids having green colored names are essential diet components, since they are not synthesized by human metabolic processes. The best food source of these nutrients is protein, but it is important to recognize that not all proteins have equal nutritional value. For example, peanuts have a higher weight content of protein than fish or eggs, but the proportion of essential amino acids in peanut protein is only a third of that from the two other sources. For reasons that will become evident when discussing the structures of proteins and peptides, each amino acid is assigned a one or three letter abbreviation.

Some common features of these amino acids should be noted. With the exception of proline, they are all 1º-amines; and with the exception of glycine, they are all chiral. The configurations of the chiral amino acids are the same when written as a Fischer projection formula, as in the drawing on the right, and this was defined as the L-configuration by Fischer. The R-substituent in this structure is the remaining structural component that varies from one amino acid to another, and in proline R is a three-carbon chain that joins the nitrogen to the alpha-carbon in a five-membered ring. Applying the Cahn-Ingold-Prelog notation, all these natural chiral amino acids, with the exception of cysteine, have an S-configuration.

For the first seven compounds in the left column the R-substituent is a hydrocarbon. The last three entries in the left column have hydroxyl functional groups, and the first two amino acids in the right column incorporate thiol and sulfide groups respectively. Lysine and arginine have basic amine functions in their side-chains; histidine and tryptophan have less basic nitrogen heterocyclic rings as substituents. Finally, carboxylic acid side-chains are substituents on aspartic and glutamic acid, and the last two compounds in the right column are their corresponding amides.

The formulas for the amino acids written above are simple covalent bond representations based upon previous understanding of mono-functional analogs. The formulas are in fact incorrect. This is evident from a comparison of the physical properties listed in the following table. All four compounds in the table are roughly the same size, and all have moderate to excellent water solublility. The first two are simple carboxylic acids, and the third is an amino alcohol. All three compounds are soluble in organic solvents (e.g. ether) and have relatively low melting points. The carboxylic acids have pKa's near 4.5, and the conjugate acid of the amine has a pKa of 10. The simple amino acid alanine is the last entry. By contrast, it is very high melting (with decomposition), insoluble in organic solvents, and a million times weaker as an acid than ordinary carboxylic acids.

Some common features of these amino acids should be noted. With the exception of proline, they are all 1º-amines; and with the exception of glycine, they are all chiral. The configurations of the chiral amino acids are the same when written as a Fischer projection formula, as in the drawing on the right, and this was defined as the L-configuration by Fischer. The R-substituent in this structure is the remaining structural component that varies from one amino acid to another, and in proline R is a three-carbon chain that joins the nitrogen to the alpha-carbon in a five-membered ring. Applying the Cahn-Ingold-Prelog notation, all these natural chiral amino acids, with the exception of cysteine, have an S-configuration.

Many unusual amino acids, including D-enantiomers of some common acids, are produced by microorganisms. These include ornithine, which is a component of the antibiotic bacatracin A, and statin, found as part of a pentapeptide that inhibits the action of the digestive enzyme pepsin.