Amino acids

Organic compounds possessing one or more basic amino groups and one or more acidic carboxyl groups. Of the more than 80 amino acids which have been found in living organisms, about 20 serve as the building blocks for the proteins. All the amino acids of proteins, and most of the others which occur naturally, are a­amino acids, meaning that an amino group (-NH₂) and a carboxyl group (-COOH) are attached to the same carbon atom. This carbon (the a carbon, being adjacent to the carboxyl group) also carries a hydrogen atom; its fourth valence is satisfied by any of a wide variety of substitutent groups, represented by the letter R in the structural formula below.

R-CH(NH₂)COOH

In the simplest amino acid, glycine, R is a hydrogen atom. In all other amino acids, R is an organic radical; for example, in alanine it is a methyl group (-CH₃), while in glutamic acid it is an aliphatic chain terminating in a second carboxyl group (-CH₂-CH-COOH). Chemically, the amino acids can be considered as falling roughly into nine categories based on the nature of R>

Occurrence. Amino acids occur in living tissues principally in the conjugated form. Most conjugated amino acids are peptides, in which the amino group of one amino acid is linked to the carboxyl group of another. Amino acids are capable of linking together to form chains of various lengths, called polypeptides. Proteins are polypep­tides ranging in size from about 50 to many thousand amino acid residues. Although most of the conjugated amino acids in nature are proteins, numerous smaller conju­gates occur naturally, many with important biological activity. The line between large peptides and small proteins is difficult to draw, with insulin (molecular weight= 7000; 50 amino acids) usually being considered a small protein and adrenocorticotropic hormone (molecular weight = 5000; 39 amino acids) being considered a large peptide.

Free amino acids are found in living cells, as well as the body fluids of higher animals, in amounts which vary according to the tissue and to the amino acid. The amino acids which play key roles in the incorporation and transfer of ammonia, such as glutamic acid, aspartic acid, and their amides, are often present in relatively high amounts, but the concentrations of the other amino acids of proteins are extremely low, ranging from a fraction of a milligram to several milligrams per 100 g wet weight of tissue. The presence of free amino acids in only trace amounts points to the existence of extraordinarily efficient regulation mechanisms. Each amino acid is ordinarily synthesized at precisely the rate needed for protein synthesis.

General properties. The amino acids are characterized physically by the follow­ing: (1) the pK₁, or the dissociation constant of the various titratable groups; (2) the isoelectric point, or pH at which a dipolar ion does not migrate in an electric field; (3) the optical rotation, or the rotation imparted to a beam of plane-polarized light (fre­quently the D line of the sodium spectrum) passing through 1 decimeter of a solution of 100 grams in 100 milliliters; and (4) solubility.

Since all of the amino acids except glycine possess a center of asymmetry at the a carbon atom, they can exist in either of two optically active, mirror-image forms, or enantiomorphs. All of the common amino acids of proteins appear to have the same configuration about the a carbon; this configuration is symbolized by the prefix L·. The opposite, generally unnatural, form is given the prefix D-. Some amino acids, such as isoleucine, threonine, and hydroxyproline, have a second center of asymmetry and can exist in four stereoisomeric forms.

At ordinary temperatures, the amino acids are white crystalline solids; when heated to high temperatures, they decompose rather than melt. They are stable in aqueous solution, and with few exceptions can be heated as high as 120°C (248°F) for short periods without decomposition, even in acid or alkaline solution. Thus, the hydrolysis of proteins can be carried out under such conditions with the complete recovery of most of the constituent free amino acids.

Biosynthesis. Since amino acids, as precursors of proteins, are essential to all organisms, all cells must be able to synthesize those they cannot obtain from their environment. The selective advantage of being able rapidly to shift from endogenous to exogenous sources of these compounds has led to the evolution of very complex and precise methods of adjusting the rate of synthesis to the available level of the compound. An immediately effective control is that of feedback inhibition. The biosyn­thesis of amino acids usually requires at least three enzymatic steps. In most cases so far examined, the amino acid end product of the biosynthetic pathway inhibits the first enzyme to catalyze a reaction specific to the biosynthesis of that amino acid. This inhibition is extremely specific; the enzymes involved have special sites for binding the inhibitor. This inhibition functions to shut off the pathway in the presence of transient high levels of the product, thus saving both carbon and energy for other biosynthetic reactions. When the level of the product decreases, the pathway begins to function once more.

The metabolic pathways by which amino acids are synthesized generally are found to be the same in all living cells investigated, whether microbial or animal. Biosynthetic mechanisms thus appear to have developed soon after the origin of life and to have remained unchanged through the divergent evolution of modern organisms.

Biosynthetic pathway diagrams reveal only one quantitatively important reac­tion by which organic nitrogen enters the amino groups of amino acids: the re­ductive amination of a-ketoglutaric acid to glutamic acid by the enzyme glutamic acid dehydrogenase. All other amino acids are formed either by transamination (transfer of an amino group, ultimately from glutamic acid) or by a modifica­tion of an existing amino acid. An example of the former is the formation of va­line by transfer of the amino group from glutamic acid to o-ketoisovaleric acid; an example of the latter is the reduction and cyclization of glutamic acid to form praline.

Importance in nutrition. The nutritional requirement for the amino acids of pro­tein can vary from zero, in the case of an organism which synthesizes them all, to the complete list, in the case of an organism in which all the biosynthetic pathways are blocked. There are 8 or 10 amino acids required by certain mammals; most plants syn­thesize all of their amino acids, while microorganisms vary from types which synthesize all, to others (such as certain lactic acid bacteria) which require as many as 18 different amino acids.