P. I. Mackenzie, D. A. Gardner-Stephen, J. O. Miners

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

11 Citations (Scopus)


The UDP-glucuronosyltransferases (UGT) are enzymes that conjugate glucuronic acid to nucleophilic O, N, S, and C atoms on lipophilic compounds via a nucleophilic bimolecular (SN2) mechanism. The aglycone substrates glucuronidated include drugs, environmental toxins, and endogenous compounds such as bilirubin and steroid hormones. The glucuronide products are water-soluble and readily excreted. There are 19 functional human UGTs belonging to two UGT families: UGT1 containing nine members and UGT2 containing seven UGT2B and three UGT2A members. These UGTs reside on the luminal side of the endoplasmic reticulum and consist of two domains, an N-terminal domain involved in substrate selection and catalysis and a C-terminal domain responsible for binding the glucuronic acid donor, UDP glucuronic acid. The UGT protein is integrated into the endoplasmic reticulum membrane by a hydrophobic series of amino acids near the C-terminus and appears to form homo- or hetero-dimers with other UGT proteins and complexes with other drug metabolizing enzymes. UGT genes are regulated by several liver-enriched transcription factors such as HNF1 and HNF4? and by ligand-activated transcription factors such as AhR, Nrf2, PXR, CAR, PPAR, FXR, and LXR. Regulation by these transcription factors ensures that each tissue or organ has a distinct complement of UGTs. Several polymorphisms in UGT genes and their regulatory regions have been shown to alter the glucuronidation capacity of tissues and organs and to be risk factors for disease and adverse drug events.

Original languageEnglish
Title of host publicationComprehensive Toxicology
EditorsCharlene A. McQueen
PublisherElsevier Inc.
Number of pages22
ISBN (Electronic)978-0-08-046884-6
ISBN (Print)9780080468686
Publication statusPublished - 12 Aug 2010


  • Gene regulation
  • Glucuronidation
  • Oligomerization
  • Polymorphisms
  • Structure-function
  • Toxicity


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