Cloning and expression of a rat liver phenobarbital-inducible UDP-glucuronosyltransferase (2B12) with specificity for monoterpenoid alcohols.
A full-length cDNA, HBPA2, that encodes for a new rat hepatic UDP-glucuronosyltransferase protein, designated UGT2B12, was isolated from a rat liver cDNA library. The isolated clone contains a 1590-nucleotide open reading frame flanked by 2 and 252 base pairs of 5' and 3' noncoding sequences, respectively. Human embryonic kidney 293 cells transfected with UGT2B12 expressed a protein with a subunit molecular mass of 53 kDa. The expressed protein catalyzed the glucuronidation of monoterpenoid alcohols, such as (-)-borneol, (+)-menthol, and (-)-nopol. In addition, a number of simple phenolic compounds, such as hydroxybiphenyls, 7-hydroxylated coumarins, p-nitrophenol, and food-derived substances (e.g., naringenin and eugenol), were also substrates for the expressed enzyme. Northern blot analysis showed that treatment of rats with phenobarbital increased hepatic mRNA levels for UGT2B12 approximately twofold. In addition to liver, Northern blot analysis demonstrated that UGT2B12 mRNA is present in kidney and testis.
Green
M D
MD
Department of Pharmacology, University of Iowa, Iowa City 52242, USA.
Clarke
D J
DJ
Oturu
E M
EM
Styczynski
P B
PB
Jackson
M R
MR
Burchell
B
B
Tephly
T R
TR
D000438:Alcohols / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004790:Enzyme Induction; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008969:Molecular Sequence Data; D010634:Phenobarbital / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013379:Substrate Specificity; D013729:Terpenes / Q000378:metabolism*; D014018:Tissue Distribution; D015262:Xenobiotics / Q000378:metabolism
D000438:Alcohols; D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013729:Terpenes; D015262:Xenobiotics; D014453:Glucuronosyltransferase; D010634:Phenobarbital