Human Liver Cytochrome P-450 Enzymes and Their Implications to Oxidation of Drugs, Toxic Chemicals and Carcinogens.

Abstract

Human liver microsomes contain multiple forms of cytochrome P-450 (P-450), and the individual P-450 forms have considerable, but overlapping, substrate specificities. In contrast to experimental animals human shows large interindividual variations in P-450-catalyzed drug oxidations, and these variations have sometimes been recognized as risk factors in individuals to cause drug-induced toxicity, carcinogenesis and teratogenesis. Thus, the efforts have been made to purify several P-450 enzymes in the human liver, and to characterize these enzymes involved in the metabolism of drugs, toxic chemicals and environmental carcinogens. Recent interests have also been focused on the isolation of cDNA clones coding several human P-450 enzymes and on the characterization and regulation of the gene products using recombinant DNA technology. This review is, therefore, undertaken to summarize recent progress in human liver P-450 enzymes involved in the oxidation of chemicals which are of environmental interest. The biochemical properties and possible roles of individual human P-450 enzymes are described considerably.