The amino acids
This chapter discusses amino acids, which are the building materials for the proteins that are the most characteristic constituents of living matter and among the most complex substances known. Proteins are irregular polymeric compounds made up from a selection of 20 different amino acids joined together by peptide linkages. They may contain anything from one hundred to several thousand amino acid units joined in a specific genetically determined order, and each protein has unique chemical and biological properties. The amino acids are amphoteric compounds and contain both a potentially basic amino (—NH2) group and a potentially acidic carboxyl (—COOH) group. Certain features of the individual amino acids have an important bearing on the structure and function of proteins. The properties and reactions of the amino acids may be broadly divided into three types: those due to the presence of (1) the acidic α—COOH group, (2) the basic α-NH2 group, and (3) the side-chain grouping.
The amino acids are the building materials for the proteins which are the most characteristic constituents of living matter and among the most complex substances known. Proteins are irregular polymeric compounds made up from a selection of twenty different amino acids joined together by peptide linkages. They may contain anything from one hundred to several thousand amino acid units joined in a specific genetically determined order and each protein has unique chemical and biological properties.
The amino acids are amphoteric compounds and, as the name suggests, contain both a potentially basic amino (–NH2) group and a potentially acidic carboxyl (–COOH) group. All the amino acids found in proteins are α–amino acids, the –NH2 and –COOH groups both being attached to the α-carbon atom. They conform to the general formula:
All the amino acids except glycine (in which R = H) contain at least one asymmetric carbon atom, i.e. one that has four different groups attached to it and exist in stereoisomeric forms. The amino acids in proteins belong to the L-series, since they are related in their three-dimensional configuration to the reference compound L-glyceraldehyde (page 91). The D and L forms, which are mirror images of each other and cannot be superimposed, may be represented on a flat sheet of paper as shown in Figure 4.1. The hatched circle represents the asymmetric C atom which is in the plane of the paper, and the –COOH and R– groups of the amino acid project behind the plane of the paper and the –H and –NH2 in front of it.
The side chains of the amino acids, which are designated in the above formula as R, are of many different types. Several contain reactive groupings such as a second acidic or basic grouping, or a hydroxyl, amide or thiol group or a heterocyclic ring. Others have aliphatic and aromatic side chains that are strongly hydrophobic. The common ancestry of living organisms is indicated by the finding that the same twenty amino acids occur in the proteins of all living forms. Although rather more amino acids are known to occur in the entire range of proteins there are only twenty whose occurrence and arrangement in peptide chains are determined by the genetic coding mechanism.
|hydroxyl (–OH)||serine, threonine and tyrosine|
|acid amide (-CONH2)||asparagine and glutamine|
|others||tryptophan and methionine (contains S)|
In the simplest of the amino acids, glycine, the radical R is a hydrogen atom. For various reasons glycine is not a very typical amino acid. More typical is α-alanine (where R = CH3) from which all the other amino acids found in proteins may be regarded as being derived by substitution on the CH3– group.
Valine, leucine and isoleucine have branched hydrocarbon side chains which are unreactive and hydrophobic. Phenylalanine has a bulky aromatic side chain and this too is hydrophobic. As a result of their water-repellant properties these amino acids tend to orientate towards the interior of folded polypeptide chains.
Another of the amino acids with an essentially unreactive side chain is proline. Strictly speaking proline is not an amino acid but a cyclic secondary amino acid and it is commonly, but incorrectly, called an imino acid. It contains a pyrrolidine ring and may be visualized as being derived from norvaline, a straight chain amino acid containing five carbon atoms in which the amino group has become involved in ring formation with the δ-C atom.
Replacement of one of the H atoms on C-4 by a hydroxyl group gives hydroxyproline, which is found in the connective tissue proteins collagen and elastin but not in other proteins. As will be apparent later, the ring structure of proline and hydroxyproline imposes certain restrictions on the folding of the polypeptide chain in their vicinity.
The acidic amino acids, aspartic acid and glutamic acid, represent the aminated forms of oxaloacetic and α-oxoglutaric acids respectively and have two carboxyl groups but only one amino group. Like other amino acids, when they are present in peptide chains the amino group
and the α–COOH group are unreactive since they are combined in peptide linkage (page 39) with the adjacent amino acids. However, the second (β or γ) –COOH group remains free and reactive.
Three of the amino acids that occur in proteins, lysine, arginine and histidine, contain an amino or substituted amino group in their side chains which gives them basic properties, i.e. enables them to act as proton acceptors.
chains. Its derivatives include hydroxylysine, desmosine and isodesmosine (Chapter 27). Ornithine, a lower homologue of lysine, which contains five instead of six carbon atoms is not found in proteins although small quantities occur free in the liver where it is involved in the synthesis of urea.
Arginine is even more strongly basic than lysine owing to the presence of the guanidino group. No protein has yet been discovered which does not contain arginine. The free amino acid, like ornithine, is involved in the urea cycle. Histidine owes its basic properties to the presence of