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Cytochromes P-450 and b5 pp 405–434Cite as

Role of Cytochrome b5 in the NADH Synergism of NADPH-Dependent Reactions of the Cytochrome P-450 Monooxygenase System of Hepatic Microsomes

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 58))

Abstract

Two systems are known to transfer electrons in hepatic microsomes: 1) the NADPH-dependent cytochrome P-450 monooxygenase system, and 2) the NADH dependent cytochrome b5 system. Their coexistence in the same organelle suggested to Estabrook and associates (Estabrook et al., 1971; Hildebrandt and Estabrook, 1971) that the systems might interact during the oxidation of drug substrates in much the same way electron transfer systems interact in mitochrondria. As evidence for the interaction of the two systems, they showed that the rate of NADH oxidation by liver microsomes was enhanced in the presence of NADPH and drug substrate, and that the rate of oxidation of NADH was related to the rate of oxidation of the substrate. They further implicated cytochrome b5 in cytochrome P-450 monooxygenase reactions by showing that the steady state of reduced cytochrome b5 in the presence of NADPH and NADH was decreased by the addition of drug substrate. Other experiments eliminated some alternative possibilities that might explain these observations, e.g., the possibility that NADH was converted to NADPH, or that NADH was sparing NADPH used in competing reactions occurring simultaneously in microsomes.

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Authors and Affiliations

  1. Department of Pharmacology, Medical School, University of Minnesota, Minneapolis, Minnesota, 55455, USA

    G. J. Mannering

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  1. G. J. Mannering
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Editors and Affiliations

  1. Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

    David Y. Cooper  & Otto Rosenthal  & 

  2. Department of Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Robert Snyder  & Charlotte Witmer  & 

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© 1975 Plenum Press, New York

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Mannering, G.J. (1975). Role of Cytochrome b5 in the NADH Synergism of NADPH-Dependent Reactions of the Cytochrome P-450 Monooxygenase System of Hepatic Microsomes. In: Cooper, D.Y., Rosenthal, O., Snyder, R., Witmer, C. (eds) Cytochromes P-450 and b5 . Advances in Experimental Medicine and Biology, vol 58. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9026-2_29

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  • DOI: https://doi.org/10.1007/978-1-4615-9026-2_29

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-9028-6

  • Online ISBN: 978-1-4615-9026-2

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