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Review ArticleMINIREVIEW

Genetic Multiplicity of the Human UDP-Glucuronosyltransferases and Regulation in the Gastrointestinal Tract

Robert H. Tukey and Christian P. Strassburg
Molecular Pharmacology March 2001, 59 (3) 405-414; DOI: https://doi.org/10.1124/mol.59.3.405
Robert H. Tukey
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Christian P. Strassburg
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Abstract

The metabolism of ingested foods and orally administered drugs occurs in the hepato-gastrointestinal tract. This process is facilitated by several supergene families that catalyze oxidative metabolism as well as conjugation of the small molecular weight substances that enter the systemic circulation through resorption in the gastrointestinal tract. The catalytic action carried out by one of several conjugation reactions leads to the eventual elimination of the resultant metabolites from the cell. As early as 1959 (R. T. Williams,Detoxification Mechanisms) it was suggested that the detoxification of most agents is efficiently performed by the phase II conjugation reactions, because the addition of bulky, water-soluble groups to the target substrates facilitates the partitioning of these metabolites from the lipid into the aqueous compartments of the cell. The combined efforts of the phase II reactions provides remarkable redundancy in a biological system that seems to be designed to assure that many endogenously generated catabolic products as well as exogenous agents introduced through the surface tissues of the digestive tracts are efficiently removed through excretion to the bile or urine. In this review, we focus on recent findings that highlight the genetic multiplicity and regulatory patterns of the phase II superfamily UDP-glucuronosyltransferases (UGTs). Although much is known regarding the number of UGTs that make up the UGT1 andUGT2 gene families, as demonstrated after the characterization of expressed cDNAs, examples are also presented in which information obtained from the human genome project will aid in the final characterization of the genetic multiplicity. In addition, tools have now been developed and examples presented to identify the expression patterns of the UGTs in human tissues, paying particular attention to expression patterns of these genes in the hepato-gastrointestinal tract.

Footnotes

    • Received December 19, 2000.
    • Accepted December 19, 2000.
  • Send reprint requests to: Robert H. Tukey, Ph.D., Departments of Pharmacology, Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093-0635. E-mail:rtukey{at}ucsd.edu

  • This work was supported in part by National Institutes of Health Grants GM49135 and CA79834 (R.H.T.) and Grant STR493/13–3 from the Deutsche Forschungsgemeinschaft (C.P.S.).

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 59 (3)
Molecular Pharmacology
Vol. 59, Issue 3
1 Mar 2001
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Review ArticleMINIREVIEW

Genetic Multiplicity of the Human UDP-Glucuronosyltransferases and Regulation in the Gastrointestinal Tract

Robert H. Tukey and Christian P. Strassburg
Molecular Pharmacology March 1, 2001, 59 (3) 405-414; DOI: https://doi.org/10.1124/mol.59.3.405

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Review ArticleMINIREVIEW

Genetic Multiplicity of the Human UDP-Glucuronosyltransferases and Regulation in the Gastrointestinal Tract

Robert H. Tukey and Christian P. Strassburg
Molecular Pharmacology March 1, 2001, 59 (3) 405-414; DOI: https://doi.org/10.1124/mol.59.3.405
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  • Article
    • Abstract
    • Characterization of the UGTS
    • Genetic Multiplicity
    • Regulation of Human UDP-Glucuronosyltransferases in the Hepato-Gastrointestinal Tract
    • Polymorphic Interindividual Regulation of UGT Genes in the Gastrointestinal Tract.
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