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Liver-Enriched Transcription Factors and Their Role in Regulating UDP Glucuronosyltransferase Gene Expression

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Variations in the capacity to detoxify carcinogens and other environmental toxins, and to eliminate drugs and waste products of metabolism, are likely to have significant effects on health and drug efficacy. As the UDP glucuronosyltransferases metabolize many of these substances to less toxic glucuronides, variations in UGT expression are likely to be important in maintenance of health and therapeutic outcomes. The factors that regulate UGT gene expression are beginning to be identified. From among these factors, the Liver-Enriched Transcription Factors (LETFs), including Hepatocyte Nuclear Factors 1 and 4α, have a major role in UGT regulation in the major sites of drug metabolism, the liver and gastrointestinal tract. This review will describe what is currently known about these LETFs and their role in UGT gene expression. It is likely that polymorphisms in LETFs and the sites to which they bind in UGT genes, may impact on drug induced disease and drug therapy.

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Keywords: CAAT-enhancer binding protein; UDP glucuronosyltransferase; gene regulation; hepatocyte nuclear factor; liver-enriched transcription factors

Document Type: Research Article

Publication date: June 1, 2008

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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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