CYP 2C19 and UDP-glucuronosyltransferases not only for drugs but also for endobiotics.

Abstract

Drug metabolism is under the control of many enzymes, essentially cytochromes P450 (CYP) catalyzing oxidation in phase I and transferases catalyzing the addition of UDPGA or glutathione in phase II. Transporter enzymes (phase III) are part of the system. All these enzymes also transform xenobiotic from our environment, including food constituents. An interesting theory based on the localization of these enzymes in their protective organs is their role against external aggressions (liver, intestine, lung, kidney, and skin). But all these enzymes also have an important role in humans’ overall metabolism and disposition of a wide range of endogenous constituents, including steroid hormones (estrogen and testosterone), vitamin D, cholesterol, and fatty acids. Human UDP-glucuronosyltransferases (UGTs) are also involved in steroid and biliary acid metabolism. All these enzyme families metabolizing drugs and xenobiotics and the endogenous metabolites compete directly for drug targets or regulatory domains of dedicated receptors, particularly the nuclear ones. It is evident that the possibilities of interactions between exogenous and endogenous metabolites are a potential safety problem. We would like to take, as example, CYP2C (CYP2C19) and UGTs for which new roles in human metabolism have been described.