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NADPH-Cytochrome P450 Reductase: Function

  • Chapter
Cytochrome P450

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 105))

Abstract

In 1950, a report was published describing the isolation of a protein involved in the reduction of cytochrome c in animal tissue (Horecker 1950). The search for this enzyme was prompted by the previous discovery of an NADPH-cytochrome c reductase in yeast (Haas et al. 1940). The yeast enzyme was shown to use NADPH as the source of reducing equivalents, and contained flavin mononucleotide (FMN) as a prosthetic group. This newly discovered enzyme was isolated from an acetone powder of pig liver after trypsin treatment. It had a molecular weight of 68000, used NADPH as its source of reducing equivalents, and was reported to contain the prosthetic group flavine adenine dinucleotide (FAD). The flavin was shown to be a necessary cofactor, since its removal from the enzyme led to the elimination of its cytochrome c reductase activity. Addition of either FMN or FAD to the apoenzyme led to its reactivation. The reductase was subsequently found to be located in the microsomal fraction (Phillips and Langdon 1962; Williams and Kamin 1962). These earlier findings provided the setting for raising a number of questions concerning reductase function: Since cytochrome c is located in the mitochondria, what is the physiological substrate for NADPH-cytochrome c reductase? How many flavins are actually present, and how are they involved in the electron transfer process? The reductase is now commonly called NADPH-cytochrome P450 reductase, referring to the endogenous electron acceptor, cytochrome P450.

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Authors
  1. W. L. Backes
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Editors and Affiliations

  1. Department of Pharmacology, MC 1505, University of Connecticut Health Center, 263 Farmington Avenue, 06030, Farmington, CT, USA

    John B. Schenkman Ph.D.

  2. Institut für Toxikologie, Gesellschaft für Strahlen- und Umweltforschung mbH, Ingolstädter Landstr. 1, W-8042, Neuherberg, Fed. Rep. of Germany

    Helmut Greim M.D.

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© 1993 Springer-Verlag Berlin Heidelberg

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Backes, W.L. (1993). NADPH-Cytochrome P450 Reductase: Function. In: Schenkman, J.B., Greim, H. (eds) Cytochrome P450. Handbook of Experimental Pharmacology, vol 105. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77763-9_2

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  • DOI: https://doi.org/10.1007/978-3-642-77763-9_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-77765-3

  • Online ISBN: 978-3-642-77763-9

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