[Role of human cytochrome P-450 enzymes in the metabolism of xenobiotics].

Cytochrome P450 enzymes play essential role in metabolism of exogenous compounds. They are found mainly in endoplasmic reticulum of hepatocytes. Purification of different P450 isoforms and determination of their structures and catalytic activities allowed to investigate their participation in metabolism of xenobiotics. Numerous factors cause variations in the expression of these P450: the effect of genetic and environmental factors results in the production of series of enzymes catalyzing biotransformation of xenobiotics. Several genetic polymorphisms have been described: CYP2D6, CYP2C and 'Ah locus' polymorphism. Some P450 (CYP1A, CYP3A, CYP2E1) are inducible by xenobiotics. Additionally, P450 expression and inducibility vary depending on tissues. It is now possible to determine which isoform(s) is (are) responsible for the production of a metabolite and to predict the fate of a compound in vivo.