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Oxidizing Intermediates in P450 Catalysis: A Case for Multiple Oxidants

  • Anuja R. Modi
  • John H. DawsonEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 851)

Abstract

Cytochrome P450 (P450 or CYP) catalysis involves the oxygenation of organic compounds via a series of catalytic intermediates, namely, the ferric-peroxo, ferric-hydroperoxo, Compound I (Cpd I) and FeIII−(H2O2) intermediates. Now that the structures of P450 enzymes have been well established, a major focus of current research in the P450 area has been unraveling the intimate details and activities of these reactive intermediates. The general consensus is that the Cpd I intermediate is the most reactive species in the reaction cycle, especially when the reaction involves hydrocarbon hydroxylation. Cpd I has recently been characterized experimentally. Other than Cpd I, there is a multitude of evidence, both experimental as well as theoretical, supporting the involvement of other intermediates in various types of oxidation reactions. The involvement of these multiple oxidants has been experimentally demonstrated using P450 active-site mutants in epoxidation, heteroatom oxidation and dealkylation reactions. In this chapter, we will review the P450 reaction cycle and each of the reactive intermediates to discuss their role in oxidation reactions.

Keywords

Cytochrome P450 Reaction cycle Compound I Ferric-peroxo Ferric-hydroperoxo Reactive intermediates Multiple oxidants 

Notes

Acknowledgment

The NIH (GM-26730) has supported cytochrome P450 research in the Dawson laboratory. We would like to thank Dr. Masanori Sono for pertinent advice.

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryUniversity of South CarolinaColumbiaUSA

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