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Molecular Mechanisms Regulating the Mitochondrial Targeting of Microsomal Cytochrome P450 EnzymesMolecular Mechanisms Regulating the Mitochondrial Targeting of Microsomal Cytochrome P450 Enzymes

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Cytochrome P450 enzymes (CYPs) are a superfamily of monooxygenases found in almost all living organisms. CYPs are predominantly localized in the endoplasmic reticulum membranes as integral membrane proteins, where they metabolize a variety of endogenous and xenobiotic compounds. CYPs also reside in other subcellular compartments, including the plasma membranes and mitochondria. CYP localization in mitochondria is regulated in one of two ways: (1) direct targeting of inherent CYPs with canonical mitochondrial signals in their protein sequence after synthesis in the cytosol or (2) mitochondrial localization of microsomal CYPs after processing of the NH2-terminal region. Microsomal CYPs targeted to mitochondria demonstrate conventional or altered catalytic activities using electrons provided by the mitochondrial electron transport system. Mechanisms of microsomal CYP targeting to mitochondria, regulation of localization, and the implications of these in drug metabolism are described in the present review.

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Keywords: AdR; Adx; B cell-associated protein 31; BAP31; EET-EAs; ER membrane; Hsp70; Hsp90; Microsomal CYP2E1; Mitochondrial CYPs; N-demethylation; NADPH; O-dealkylation; S-oxidation; adrenodoxin reductase; anti-convulsants; anti-depressants; bile acid bio-syntheses; cytochrome P450; dealkylation; deamination; drug metabolism; electron transport system; endoplasmic reticulum membranes; epoxidation; erythromycin; human CYP11A1; hydroxylation; microsome; mitochondria; mitochondrial; mitochondrial CYP; monooxygenases; monooxygenation; mtCYP2E1; opiates; pregnenolone; pro-tein kinase; rat microsomal CYP1A1; signal sequence; steroid hormone biosynthesis; targeting; xenobiotic

Document Type: Research Article

Publication date: December 1, 2010

More about this publication?
  • 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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