Cytochrome P450. Mechanisms of action and clinical implications

Abstract

The term cytochrome P450 refers to a group of hemoproteins whose Fe(2+)-carbon monoxide complex shows an absorption spectrum with a maximum near 450 nm. There is a broad interest in the P450s because of their significance in a variety of disciplines ranging from medical genetics to inorganic chemistry. Cytochrome P450 enzymes are involved in the metabolism of drugs, carcinogens, steroids, pesticides, hydrocarbons and natural products. The toxicity of many of these products may be modulated, either via replacement or by the various oxidations catalyzed by the cytochrome P450 enzymes. In recent years the roles of cytochrome P450 enzymes in the metabolism of endogenous compounds have been partially elucidated. Physiological compounds such as steroids, fatty acids, prostanoids and other eicosanoids, fat-soluble vitamins and mammalian alkaloids have been shown to be substrates. Aside from their roles in metabolism, certain of these enzymes were found to be involved in the metabolic activation of a variety of chemical carcinogens and possibly in the overall process of chemical carcinogenesis. Studies show that alterations in cytochrome P450 activities toward various substrates have been implicated in diseases which affect human health. The roles are reviewed of the various cytochrome P450 enzymes in the metabolism of substrates which may be associated with clinical disease states.