[Human cytochromes P450. Applications in pharmacology]

Cytochromes P450 (P450) are hemoproteins which catalyze essentially monooxygenation reactions. These enzymes may metabolize either endogenous compounds such as steroids, or exogenous compounds. This review will concentrate on P450 metabolizing xenobiotics. They are found mainly in endoplasmic reticulum of hepatocytes. Purification and cloning of the different isoforms allowed to set up an international nomenclature based on sequences similarities between these P450. Ten families are known in mammals and 4 (CYP 1 to 4) metabolize xenobiotics. Each family may include several subfamilies (A, B, ...). Numerous factors cause variations in the expression of these P450: genetic, environmental, physiopathologic. Several genetic polymorphism have been described, P450, 2D6, 2C and may be 1A2 and 2E1. Some P450 (3A, 1A, 2E, ...) are inducible by compounds such as phenobarbital, rifampicin, aromatic hydrocarbon, ethanol, or omeprazole. Finally, P450 expression and inducibility vary depending on tissues. It is now possible to determine which isoform(s) is (are) responsible of the production of a metabolite. Specific tests are now available to evaluate the level of P450 in vivo in man (1A, 3A, 2D6, 2C).