Multiple oxidants in cytochrome P450 catalyzed reactions: implications for drug metabolism.
The activation of molecular oxygen by Cytochromes P450 to the ultimate mono-oxygen oxidant species involves three distinct dioxygen species coordinated to the heme iron. These intermediates have different chemical properties, and have recently been proposed to participate in some Cytochrome P450-catalyzed oxidation reactions. This article reviews the extent of our current knowledge on the roles proposed for the heme- peroxo, hydroperoxo, and superoxo complexes in various reactions. The extent to which such species contribute to the breadth of reactions catalyzed by Cytochrome P450 has yet to be defined, and more definitive experiments are needed to establish such species in the reactions they are proposed to effect.
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Candidate Enhancement Biology, Pfizer Global Research and Development, Groton, CT 06340, USA. vaza@groton.pfizer.com
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D016877:Oxidants / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D016877:Oxidants; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System