Concepts: Amino acids and proteins

3.1 Amino acids

An amino acid carries an amino group and an acidic carboxyl group on the same carbon, the alpha carbon, which is why it is called an alpha-amino acid. That carbon is a substituted methane with four groups attached: a hydrogen, a carboxyl group, an amino group and a variable side chain, the R group. The R group decides which amino acid it is. Glycine has hydrogen as its R group, alanine has a methyl group and serine has a hydroxymethyl group. Proteins are built from twenty kinds of amino acids, so the R group set in proteins is limited, even though many more amino acids exist in nature.

The behaviour of an amino acid follows its functional groups. If the R group adds acidic groups, the amino acid behaves as acidic; if it adds basic groups, the amino acid is basic; and a neutral amino acid has no such excess. Aromatic amino acids such as tyrosine, phenylalanine and tryptophan carry rings. The amino and carboxyl groups can both ionise, so the structure of an amino acid changes with pH. At a particular pH the molecule carries both a positive and a negative charge at once, and this form is called the zwitterionic form.

3.1.1 The peptide bond

Amino acids join when the carboxyl group of one reacts with the amino group of the next, and the link is a peptide bond, with water released. A chain of amino acids joined this way is a polypeptide, and a protein is a polypeptide with a defined sequence. Because there are twenty possible units at each position, a protein is a heteropolymer, not a homopolymer. Some amino acids cannot be made by the human body and must come from food; these are the essential amino acids, while the non-essential ones can be made in the body.

3.1.2 Four levels of structure

The sequence of amino acids in a protein is its primary structure: which amino acid is first, which is second, and so on. The first amino acid carries the free amino group and is the N-terminal end; the last carries the free carboxyl group and is the C-terminal end. The primary structure is written as a line from N to C.

The secondary structure is the local folding of the chain. Some parts of a protein coil into a helix like a spiral staircase, and only right-handed helices appear in proteins; other parts fold into a beta-pleated sheet. Tertiary structure is the folding of the whole long chain upon itself into a compact three-dimensional shape, like a hollow woollen ball, and this level is necessary for the protein's biological activity. Some proteins are assemblies of more than one polypeptide, and the arrangement of the folded subunits with respect to one another is the quaternary structure. Adult human haemoglobin is the standard example: two alpha and two beta subunits, four in all.

3.1.3 What proteins do

Proteins are the working molecules of the body. Collagen, the most abundant protein in the animal world, forms the ground substance between cells. Trypsin is an enzyme, insulin is a hormone and antibodies fight infection. Receptors receive signals such as smells and hormones, and the GLUT-4 protein lets glucose enter cells. RuBisCO, the most abundant protein in the whole biosphere, catalyses the first step of carbon fixation in photosynthesis. The same chapter that gives the structure therefore also gives the range: a protein's shape decides its job, and the fold is decided by the sequence.

3.1.4 The link between sequence and shape

The primary sequence is the key to everything that follows, because the order of amino acids decides where the chain folds and which groups sit near each other. Two proteins with different sequences therefore fold into different shapes and carry out different jobs, even when they use the same twenty amino acids. Warmth, pH extremes and some chemicals break the fold, and the protein loses its function even though its primary sequence is unchanged. That is why a protein's shape is described as its active form, and why denaturation is the loss of that shape.

3.1.5 Folding and unfolding

The folded shape of a protein is held together by weak bonds and a few strong ones. Hydrogen bonds steady the helices and sheets, disulphide bonds link distant parts of the chain, and ionic and hydrophobic interactions pull the surface into its final form. Heat or an extreme pH breaks these interactions, and the chain unfolds; the protein is then denatured and loses its activity even though its amino acid sequence is unchanged. This is why a fever is dangerous and why an enzyme has a narrow working range: both depend on a shape that survives only inside a narrow set of conditions.