Cytochromes P450, Drugs, and Diseases

  1. F. Peter Guengerich
  1. Department of Biochemistry and Center in Molecular Toxicology Vanderbilt University School of Medicine 638 Robinson Research Building Nashville, TN 37232-0146

Abstract

The human genome encodes fifty-seven cytochrome P45O (P45O, or CYP) proteins. The majority of these are involved in the metabolism of steroids, bile acids, fatty acids, eicosanoids, and fat-soluble vitamins. Nearly fifteen P45Os are involved in the metabolism of drugs and other xenobiotic chemicals and have received the most attention from pharmacologists. Many issues exist as to how to most logically deal with the major human P45Os in the context of the drug development process. Many of these same xenobioticmetabolizing P45Os also activate carcinogens, but the in vivo significance of such activation in cancer etiology has been difficult to assess because of the complexities of tumorigenesis. The functions of the remaining fifteen P45O "orphans" are unknown and represent an area in need of much study.1

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