CYTOCHROME P450 REDUCTASE

Todd D. Porter, Ph.D.

NADPH-cytochrome P450 reductase (CPR) is the electron donor protein for several oxygenase enzymes found on the endoplasmic reticulum of most eukaryotic cells.  These oxygenases include the cytochromes P450, a family of enzymes involved in the metabolism of many drugs and dietary substances, and in the synthesis of steroid hormones and other extracellular lipid signaling molecules; heme oxygenase, a hemeprotein that catalyzes the first step in the degradation of heme to bilirubin; and squalene monooxygenase, the second enzyme in the committed pathway for sterol biosynthesis.  CPR may also donate electrons to 7-dehydrocholesterol reductase in the sterol synthesis pathway, and to cytochrome b₅, which supports both sterol synthesis and the fatty acid desaturase and elongase pathways.

CPR is a flavoprotein containing both FAD and FMN.  It has a modular structure suggestive of its evolution from smaller subunits similar to flavodoxins and ferredoxin NADP⁺ reductase, and its 3-dimensional structure was recently determined.  CPR is also a component of nitric oxide synthases and methionine synthase reductase.  My laboratory is carrying out structural studies on this unique flavoprotein through site-directed mutagenesis, with the goal of generating biotechnological applications for this versatile reductase.

• Biology of Cytochrome P450 Reductase
  

  • Discovery and characterization

  • Expression and regulation

  • Analysis of the CPR gene
    
    

• Enzymology of Cytochrome P450 Reductase
  

  • Flavins and electron transfer

  • NADPH binding

  • Electron transfer to cytochrome P450
    
    

• Structure of Cytochrome P450 Reductase

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