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Structure and Function of Cytochrome P-450

  • F. Peter Guengerich
  • Tsutomu Shimada
  • Diane R. Umbenhauer
  • Martha V. Martin
  • Kunio S. Misono
  • Linda M. Distlerath
  • Paul E. B. Reilly
  • Thomas Wolff
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)

Abstract

Cytochrome P-450 (P-450) is a hemoprotein that catalyzes the oxidation of a wide variety of substrates, some of which are converted to reactive products that can be attacked by cellular nucleophiles or solvolyzed (Guengerich and Liebler, 1985). Much has been learned about the isozymes in this family of hemoproteins from studies with microorganisms and experimental animals. Biochemical studies with humans were started shortly after the discovery of P-450, and a number of catalytic activities have been ascribed to P-450 in humans (Boobis and Davies, 1984). One of the first efforts at the purification of human cytochrome P-450 was that of Kaschnitz and Coon (1975), which was followed up by several other studies. Our own laboratory has been involved in the purification of several isozymes of human as well as rat liver P-450 (Wang et al., 1980, Wang et al., 1983; Guengerich et al., 1982; Distlerath et al., 1985; Guengerich et al., 1985). In the earlier efforts catalytic activity data were difficult to evaluate because most of the assays were not specific to individual P-450 isozymes (Wang et al., 1980, 1983). More recently we have focused our efforts on the biochemical characterization of human P-450s which are involved in polymorphisms of drug metabolism. Such genetic polymorphisms, studied extensively by Smith and Idle and their associates (Ayesh et al., 1984). provide an opportunity for directly relating biochemical studies to in vivo situations and for focusing on the regulation of specific P-450 isozymes and their catalytic activities. We report here the purification of four such human liver P-450s and studies on their catalytic specificity.

Keywords

Human Liver Congenital Adrenal Hyperplasia Human Liver Microsome Human Cytochrome Human Liver Cytochrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • F. Peter Guengerich
    • 1
  • Tsutomu Shimada
    • 1
  • Diane R. Umbenhauer
    • 1
  • Martha V. Martin
    • 1
  • Kunio S. Misono
    • 1
  • Linda M. Distlerath
    • 1
  • Paul E. B. Reilly
    • 1
  • Thomas Wolff
    • 1
  1. 1.Department of Biochemistry and Center in Molecular Toxicology VanderbiltUniversity School of MedicineNashvilleUSA

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