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Regioselective Versatility of Monooxygenase Reactions Catalyzed by CYP2B6 and CYP3A4: Examples with Single Substrates

  • Claudio A. Erratico
  • Anand K. Deo
  • Stelvio M. BandieraEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 851)

Abstract

Hepatic microsomal cytochrome P450 (CYP) enzymes have broad and overlapping substrate specificity and catalyze a variety of monooxygenase reactions, including aliphatic and aromatic hydroxylations, N-hydroxylations, oxygenations of heteroatoms (N, S, P and I), alkene and arene epoxidations, dehalogenations, dehydrogenations and N-, O- and S-dealkylations. Individual CYP enzymes typically catalyze the oxidative metabolism of a common substrate in a regioselective and stereoselective manner. In addition, different CYP enzymes often utilize different monooxygenase reactions when oxidizing a common substrate. This review examines various oxidative reactions catalyzed by a CYP enzyme acting on a single substrate. In the first example, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), a halogenated aromatic environmental contaminant, was oxidatively biotransformed by human CYP2B6. Nine different metabolites of BDE-47 were produced by CYP2B6 via monooxygenase reactions that included aromatic hydroxylation, with and without an NIH-shift, dealkylation and debromination. In the second example, lithocholic acid (3α-hydroxy-5β-cholan-24-oic acid), an endogenous bile acid, served as a substrate for human CYP3A4 and yielded five different metabolites via aliphatic hydroxylation and dehydrogenation reactions.

Keywords

Cytochrome P450 Human CYP2B6 Human CYP3A4 Lithocholic acid Oxidative biotransformation Polybrominated diphenyl ethers BDE-47 and BDE-99 Hydroxylated metabolites 

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Claudio A. Erratico
    • 1
    • 2
  • Anand K. Deo
    • 1
    • 3
  • Stelvio M. Bandiera
    • 1
    Email author
  1. 1.Faculty of Pharmaceutical SciencesThe University of British ColumbiaVancouverCanada
  2. 2.Toxicology CenterUniversity of AntwerpWilrijkBelgium
  3. 3.UCB PharmaBriane l’AlleudBelgium

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