DRUG-METABOLIZING-ENZYMES RELATED TO LABORATORY MEDICINE - CYTOCHROMES P-450 AND UDP-GLUCURONOSYLTRANSFERASES

Many studies on drug metabolism have been carried out during the last decades using protein purification, molecular cloning techniques and a nalysis of polymorphisms at phenotype and genotype levels. These resea rches led to a better understanding of the role of drug metabolizing e nzymes in the biotransformation of drugs, pollutants or foreign compou nds and of their use in laboratory medicine. The metabolic processes c ommonly involved in the biotransformation of xenobiotics have been cla ssified into functionalization reaction (phase I reactions), which imp licate lipophilic compounds. These molecules are modified via monooxyg enation, dealkylation, reduction, aromatization, hydrolysis and can be substrates for the phase II reactions, often called conjugation react ions as they conjugate a functional group with a polar, endogenous com pound. This review, devoted to cytochromes P-450 (CYP) and UDP-glucuro nosyltransferases (UGT), describes essentially the genetic polymorphis ms found in humans, their clinical consequences and the methods to ass ess the phenotypes or genotypes, with a view to studying the interindi vidual differences in drug monooxygenation and drug glucuronidation. V ariations in drug glucuronidation reported here focused essentially on variations due to physiological factors, induction, drug interactions and genetic factors in disorders such as Gilbert's Syndrome and Crigl er-Najjar type I and II diseases.