Journal
TOXICOLOGY
Volume 181, Issue -, Pages 453-456Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/S0300-483X(02)00449-3
Keywords
genetic polymorphism; UDP-glucuronosyltransferase; glucuronidation
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UDP-Glucuronosyltransferase (UGT), the microsomal enzyme responsible for glucuronidation reactions, exists as a superfamily of enzymes. Genetic polymorphism has been described for 6 of the 16 functional human UGT genes characterised to date, namely UGT 1A1, IA6, 1A7, 2B4, 2B7 and 2B15. Since glucuronidation is an essential pathway for the elimination of a myriad of xenobiotics and endogenous compounds, genetic polymorphism of UGT is potentially of toxicological and physiological importance. However, functional significance has only been convincingly demonstrated for genetic polymorphism of UGT1A1 Apart from impaired bilirubin glucuronidation, the mutations responsible for Gilbert syndrome also affect the elimination of a limited number of xenobiotics. It has been proposed on the basis of altered catalytic activity of mutants of UGT 1A6, 1A7 and 2B15 that genetic polymorphism of these forms may be of toxicological significance, but this is yet to be proven. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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