Uncommon P450-Catalyzed Reactions

Author: Guengerich F.Peter

Source: Current Drug Metabolism, Volume 2, Number 2, June 2001 , pp. 93-115(23)

Publisher: Bentham Science Publishers

Abstract:

Cytochrome P450 (P450) enzymes play major roles in the metabolism of drugs, carcinogens, steroids, eicosanoids, alkaloids, pesticides, and other important xenobiotics, as well as chemicals normally endogenous to the body. P450s are gene-rally considered in a classical catalytic reduction-oxidation cycle and an odd-electron abstraction/rebound chemical mechanism that can be used to rationalize carbon hydro-xylation, dealkylation of heteroatomic substrates, heteroatom oxygenation, and the oxidation of unsaturated compounds to epoxides and phenols. However, many other reactions are catalyzed by P450s but not generally appreciated. The classical catalytic mechanism requires some expansion to explain all of these reactions. Reactions discussed here include mechanism-based heme inactivation, mechanism-based protein modification, 1,2-shifts, 1- and 2-electron reductions, 1-electron oxidation, oxidative cleavage of carboxylic acid esters, desaturation, deformylation of aldehydes, ring formation, ipso mechanisms for aryl dehalogenation and O- and N-dearylation, cis-trans bond isomerization, several rearrangements of oxidized eicosanoids, aldoxime dehydration, and hydrolysis of phosphatidylcholine.

Keywords: P450-Catalyzed Reactions; Cytochrome P450 (P450) enzymes; drugs carcinogens steroids eicosanoids alkaloids p; electron reductions,; oxidation; C-Hydroxylation; Coupling; Eicosanoids; Phospholipase D Activity; Polycyclic aromatic hydrocarbon

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389200013338694

Publication date: 2001-06-01

• Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:
  
  In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.

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