NADPH-Cytochrome P450 Reductase: Function

  • W. L. Backes
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 105)


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.


Flavine Adenine Dinucleotide P450 Reductase Electron Equivalent Reduce Nicotinamide Adenine Dinucleotide NADPH Concentration 
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© Springer-Verlag Berlin Heidelberg 1993

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  • W. L. Backes

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