RT Journal Article
SR Electronic
T1 Glucuronidation of Opioids, Carboxylic Acid-Containing Drugs, and Hydroxylated Xenobiotics Catalyzed by Expressed Monkey UDP-Glucuronosyltransferase 2B9 Protein
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1389
OP 1394
VO 25
IS 12
A1 Green, Mitchell D.
A1 Bélanger, Guy
A1 Hum, Dean W.
A1 Bélanger, Alain
A1 Tephly, Thomas R.
YR 1997
UL http://dmd.aspetjournals.org/content/25/12/1389.abstract
AB UDP-glucuronosyltransferase (UGT) 2B9, isolated from a cynomolgus monkey liver cDNA library, is 89% identical to human UGT2B7 in primary amino acid sequence, and the two expressed enzymes were previously shown to catalyze the glucuronidation of many common endogenous substrates. The purpose of the present study was to characterize the reactivity of expressed UGT2B9 with important therapeutic agents and other xenobiotics. UGT2B9, stably expressed in human embryonic kidney 293 cells, catalyzes the 3-O- and 6-O-glucuronidation of morphine and the 6-O-glucuronidation of codeine. A number of other morphinan (e.g. naloxone, naltrexone, and nalorphine) and oripavine (e.g. buprenorphine) derivatives are substrates for this enzyme. In general, morphinan derivatives are glucuronidated at higher rates, compared with oripavines; however, glucuronidation efficiency values (Vmax/KM ) for the compounds are similar. Stably expressed UGT2B9 also catalyzes the glucuronidation of profen nonsteroidal anti-inflammatory drugs, fibrate hypolipidemic agents, and straight-chain fatty acids at the carboxylic acid moiety. Monoterpenoid alcohols and propanolol are glucuronidated at aliphatic hydroxyl positions. Expressed UGT2B9 exhibits enantioselective glucuronidation for (R/S)-ibuprofen, (R/S)-propanolol, and (+)/(−)-menthol. The data suggest that monkey UGT2B9 and human UGT2B7 are functionally similar. The American Society for Pharmacology and Experimental Therapeutics