Functions and transcriptional regulation of PAH-inducible human UDP-glucuronosyltransferases

Drug Metab Rev. 1999 May;31(2):411-22. doi: 10.1081/dmr-100101927.

Abstract

Functions and regulation of selected human UDP-glucuronosyltransferases (UGT1A1, UGT1A4, UGT1A6, UGT1A9, UGT2B7, UGT2B15) are summarized. Evidence for at least two PAH-inducible UGTs (UGT1A6 and UGT1A9) is presented, which, however, are also constitutively expressed in a tissue- and cell-specific manner. These isoforms have recently been characterized to conjugate planar and bulky phenols, respectively. Using a selective RT-PCR method, UGT1A6 expression was detected in a variety of tissues (liver, kidney, lung, intestine, and pharyngeal mucosa). PAH-inducible UGTs may cooperate in the metabolism of phenolic metabolites of benzo(a)pyrene. Studies with stably expressed isoforms suggest that UGT1A9 is responsible for the formation of benzo(a)pyrene-3.6-diphenol diglucuronide, the major biliary metabolite of benzo(a)pyrene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Enzyme Induction
  • Gene Expression Regulation, Enzymologic*
  • Glucuronosyltransferase / genetics*
  • Glucuronosyltransferase / physiology
  • Humans
  • Polycyclic Aromatic Hydrocarbons / metabolism
  • Polycyclic Aromatic Hydrocarbons / pharmacology*
  • Transcription, Genetic / drug effects

Substances

  • Polycyclic Aromatic Hydrocarbons
  • Glucuronosyltransferase