1.6 Proteins

Proteins are assembled from amino acids. Each standard amino acid has a central α-carbon bonded to an amino group, a carboxyl group, a hydrogen atom and a variable R group. The common framework enables peptide-bond formation, while differences in the R group distinguish one amino acid from another.

A condensation reaction joins the carboxyl group of one amino acid to the amino group of another. An –OH from the carboxyl group and an –H from the amino group form water, while the remaining carbon and nitrogen become linked by a covalent peptide bond. Two amino acids make a dipeptide; repeated condensation produces a polypeptide with an amino terminus and a carboxyl terminus.

Ribosomes synthesize polypeptides using amino acids in an order specified by messenger RNA. Although many amino acids occur in nature, the genetic code normally incorporates a common set of twenty into proteins. Humans can synthesize some of these, but essential amino acids must be obtained in the diet because the required synthetic pathways are absent or inadequate. 'Essential' describes dietary necessity, not greater importance within a protein.

Sequence possibilities grow exponentially. A polypeptide of n positions has 20ⁿ possible sequences before considering length variation. Cells make only a minute, genetically specified subset, giving proteins effectively limitless sequence diversity.

Denaturation is loss of a protein's native higher-level conformation. Increasing temperature raises molecular motion and can disrupt hydrogen bonds, ionic interactions and hydrophobic organization. Extreme pH changes protonation and charge, breaking salt bridges and creating new repulsions. Organic solvents, detergents and heavy-metal ions can also disturb folding. The precise condition required differs among proteins.

Peptide bonds generally survive the moderate heat or pH change that denatures a protein, so primary structure remains while secondary, tertiary or quaternary structure is lost. An enzyme's active site no longer has the correct geometry; a transport protein may no longer bind its ligand; exposed hydrophobic regions may cause molecules to aggregate. The whitening and solidification of egg during cooking is visible aggregation of denatured proteins.

Denaturation is not always irreversible. Some small proteins refold if normal conditions return, demonstrating that primary sequence contains much of the information needed for folding. Others aggregate or become trapped in incorrect conformations and cannot recover without cellular chaperones, or at all. Avoid defining denaturation as death: proteins are not living, and loss of one protein's shape is a molecular event.