Functions and transcriptional regulation of PAH-inducible human UDP-glucuronosyltransferases.
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.
Bock
K W
KW
Institute of Toxicology, University of Tübingen, Germany.
Gschaidmeier
H
H
Heel
H
H
Lehmköster
T
T
Münzel
P A
PA
Bock-Hennig
B S
BS
D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000502:physiology; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D011084:Polycyclic Aromatic Hydrocarbons; D014453:Glucuronosyltransferase