[NADPH-cytochrome P450 reductase, not only the partner of cytochrome P450]

Abstract

NADPH-cytochrome P450 reductase, CPR, the enzyme of the majority of eucaryotic cells belongs to the family of diflavin reductases and is usually located in endoplasmic reticulum. This protein is build of three domains. The first one, C-terminal, binds FAD and NADPH, the second one, N-terminal, binds FMM, whereas the third one is the regulatory domain. Catalytic cycle of the enzyme runs by intermediate FMNH-FADH with the participation of conformational changes induced by NADPH binding to the active centre of the enzyme. It has been shown in mice that CPR was necessary for the action of cytochrome P450 monooxygenase system, but this system is not crucial for animal surviving. CPR participates also in electron transport to cytochrome b5, heme oxidase, squalen monooxygenase and 7-dehydrocholesterole reductase. Furthermore, its own crucial task is the catalysis of reductive metabolism of prodrugs, particularly antitumor agents.