Cytochrome P450 reductase diversity

F.P. Guengerich (2001). Diversity in mechanisms of substrate oxidation by cytochrome P450 2D6. Lack of an allosteric role of NADPH-cytochrome P450 reductase in catalytic regioselectivity. J. Biol. Chem. 276, 39553-39561. 

The discovery of c5 ochromes P450 in mammalian tissues rich with these proteins, such as liver and the adrenal gland, resulted in intense scrutiny of their roles in xenobiotic metabolism and endogenous functions. Following their discovery came the realization that mammalian proteins required electron donor systems for activity, either NADPH-cytochrome P450 reductase (CPR) or adrenodoxin and adrenodoxin reductase in the endoplasmic reticulum or the mitochondria respectively Protein biochemistry and molecular biology revealed the multiplicity of CYP forms and mammalian genomes exhibited CYP diversity. 

Metabolic activation of carcinogens involves many enzymatic systems, known as phase I enzymes. The most important is the cytochrome P450 complex, consisting of several different isoenzymes, which are particularly active in the liver. Other enzymes include peroxidases, quinone reductases, epoxide hydrolases, sulfotrans-ferases, and others. Their variety reflects the diversity of chemical structures of compounds to which an organism is exposed. These may be harmful substances or needed ones, or even those indispensable for its proper functioning. One could argue that the activation of carcinogens is an undesirable side effect of metabolic pathways,... 

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