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Xenobiotic-CoA Ligases Kinetic and Molecular Characterization

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This review focuses primarily on the mammalian medium and long-chain fatty acid coenzyme A ligases that have been implicated in the metabolism of xenobiotic carboxylic acids such as pesticides, arylpropionate non steroidal anti-inflammatory drugs and the hypolipidaemic clofibrate and its congeners. Evidence of multiplicity of mitochondrial and microsomal enzymes and their respective substrate/inhibitor profiles are discussed. For completeness, where appropriate, details of non-substrate inhibitors have also been included. Although knowledge is limited at present with respect to the medium-chain enzymes, aspects of regulation particularly the in vivo, in vitro role of peroxisome proliferators and current knowledge of the molecular biology of the long-chain fatty acid CoA ligase superfamily are documented. Additionally, alignment of thirteen cloned mammalian fatty acid CoA ligases using criteria established for the CYP and UGT superfamilies has enabled construction of a phylogenetic tree that clearly defines three families. Catalytic data are still limited and the xenobiotic substrate inhibitor profiles of the recombinant proteins are incomplete. Finally, with increasing recognition of the importance of fatty acyl-CoA esters as physiological regulators of cell function including gene expression, the review concludes with a discussion of the metabolic fate and toxicity of xenobiotic acyl-CoA esters
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Keywords: Coenzyme; Glucuronidation; Kinetics; UDP glucuronosyl transferases; Xenobiotic CoA Ligases

Document Type: Review Article

Publication date: July 1, 2000

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  • 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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