Cytochromes P450 and metabolism of xenobiotics

Cytochromes P450 (henceforth P450s) are involved in a variety of metabolic and biosynthetic processes. The number of known P450 enzymes exceeds 1000, while the endogenous substrates of most of them remain unknown. All P450 en zymes exhibit similarity in their structure and general mechanism of action ; however, there are significant differences in the detailed function of in dividual enzymes as well as in the structures and properties of their activ e sites. This review discusses the properties of the most important P450 en zymes taking part in drug metabolism in humans. P450 3A4 is of paramount im portance, because it is the most abundant P450 in the human liver and is kn own to metabolize the majority of drugs whose biotransformation is known. G enetically dependent variabilities of individual P450 activities and levels are described, documenting the importance of pharmacogenetics aimed at exp laining differences in the response of the organism to various drugs.