Physiological Functions of Cytochrome P450 in Relation to Structure and RegulationBy
- C.R. Jefcoate, Department of Pharmacology and Environmental Toxicology Center, University of Wisconsin, Madison, WI, USA
Research on the cytochrome P450 family of genes has traditionally been dominated by forms participating in drug metabolism. This has occurred in spite of early discovery of steroid hydroxy lase P450 cytochromes in the adrenal gland. More recently, contributions on the characterization and regulation of P450 cytochromes involved in biosynthetic reactions have been found at the international meetings on cytochrome P450 and in the several books on the field. Key recognition that P450 cytochromes should be recognized in a physiological context was provided by an international meeting in Jerusalem in 1991 and the subsequent publication of the proceedings in the Journal of Steroid Biochemistry and Molecular Biology (43, number 8, 92). Like this meeting, this book seeks to place equal weight on the physiological processes that are controlled by the products of reactions at usually very selective cytochrome P450 forms. Each of the authors was asked to discuss the molecular regulation of these P450 forms. Each of the authors was asked to discuss the molecular regulation of these P450 forms in the light of these physiological processes. In some cases the physiological role of the cytochrome P450 and even the natural substrate are unresolved, but a pattern of strong endocrine regulation is indicative of a hidden function. As more and more low abundance P450 genes are uncovered, the need to address potential physiological activities becomes more pressing. It is almost infinitely more difficult to identify a physiological substrate than to clone a new form.
Advances in Molecular and Cell Biology
Published: December 1996
- Contents. List of Contributors. Preface (C.R. Jefcoate). P450 Cytochromes and Hormonal Regulation: An Overview (C.R. Jefcoate). Electron Transfer Proteins of Cytochrome P450 Systems (I. Hanukoglu). The Molecular Structure of P450s: The Conserved and the Variable Elements (S.E. Graham-Lorence and J.A. Peterson). Diverse Molecular Mechanisms Regulate the Expression of Steroid Hydryxylase Genes Required for Production of Ligands for Nuclear Receptors (M.R. Waterman and D.S. Keeney). Cytochrome P450scc and Regulation of Cholesterol Conversion to Steroid Hormones (C.R. Jefacoate). The Regulation of the Formation of Glucocorticoids and Mineralocorticoids In Vivo (J. LeHoux, H. Bernard, L. Ducharme, A. Lefebvre, D. Shapcott, A. Tremblay, and S. Véronneau). Physiology and Molecular Biology of P450c21 and P450c17 (B. Chung). The Aromatase Reaction (E.R. Simpson, M.S. Mahendroo, M.W. Kilgore, G.D. Means, S.E. Bulun, M.M. Hinshelwood, and C.R. Mendelson). Regulation of Calcium Metabolism by the Vitamin D Hydroxylases (H.J. Armbrecht, R.K. Nemani, and N. Wongsurawat). The Regulation of Cholesterol Conversion to Bile Acids (J.Y.L. Chiang and Z.R. Vlahcevic). Eicosanoid Metabolism and Bioactivation by Microsomal Cytochrome P450 (J.H. Capdevila, D. Zeldin, A. Karara, and J.R. Falck). Steroid Hormones and Other Physiologic Regulators of Liver Cytochromes P450: Metabolic Reactions and Regulatory Pathways (D.J. Waxman). Index.