The role of the drug-metabolizing enzymes.

Drug-metabolizing enzymes function in the biotransformation of both endogenous and exogenous lipophilic compounds. Phylogenetic studies indicate that the drug-metabolizing enzymes were a late evolutionary development. Stimuli for the evolution of these enzymes were probably movement to a terrestrial environment, a diet of higher plants and an increasing tissue specialization, with a consequential need for the formation and inactivation of hormones, bile salts etc. Most drug-metabolizing enzymes exist in multiple forms. Some are concerned solely with the metabolism of a very limited range of endogenous lipids; others such as 'phenobarbitone-type cytochrome P-450' seem to be concerned mainly wih the metabolism of exogenous compounds. In mammals the liver and intestine have a major role in the biotransformation of exogenous compounds, whereas in other tissues the primary function of the drug-metabolizing enzymes appears to be the metabolism of endogenous lipids such as steroids, lipid-soluble vitamins and fatty acids.