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      Human UDP-glucuronosyltransferases: metabolism, expression, and disease.

      1 ,
      Annual review of pharmacology and toxicology
      Annual Reviews

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          Abstract

          In vertebrates, the glucuronidation of small lipophilic agents is catalyzed by the endoplasmic reticulum UDP-glucuronosyltransferases (UGTs). This metabolic pathway leads to the formation of water-soluble metabolites originating from normal dietary processes, cellular catabolism, or exposure to drugs and xenobiotics. This classic detoxification process, which led to the discovery nearly 50 years ago of the cosubstrate UDP-glucuronic acid (19), is now known to be carried out by 15 human UGTs. Characterization of the individual gene products using cDNA expression experiments has led to the identification of over 350 individual compounds that serve as substrates for this superfamily of proteins. This data, coupled with the introduction of sophisticated RNA detection techniques designed to elucidate patterns of gene expression of the UGT superfamily in human liver and extrahepatic tissues of the gastrointestinal tract, has aided in understanding the contribution of glucuronidation toward epithelial first-pass metabolism. In addition, characterization of the UGT1A locus and genetic studies directed at understanding the role of bilirubin glucuronidation and the biochemical basis of the clinical symptoms found in unconjugated hyperbilirubinemia have uncovered the structural gene polymorphisms associated with Crigler-Najjar's and Gilbert's syndrome. The role of the UGTs in metabolism and different disease states in humans is the topic of this review.

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          Author and article information

          Journal
          Annu Rev Pharmacol Toxicol
          Annual review of pharmacology and toxicology
          Annual Reviews
          0362-1642
          0362-1642
          2000
          : 40
          Affiliations
          [1 ] Department of Chemistry & Biochemistry, Cancer Center, University of California, San Diego, La Jolla 92093, USA. rtukey@ucsd.edu
          Article
          10.1146/annurev.pharmtox.40.1.581
          10836148
          7da800ed-eca6-4fc9-ae22-0b33dafb17c0
          History

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