RT Journal Article
SR Electronic
T1 Human UGT2B7 Catalyzes Morphine Glucuronidation
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1
OP 4
VO 25
IS 1
A1 Birgit L. Coffman
A1 Gladys R. Rios
A1 Christopher D. King
A1 Thomas R. Tephly
YR 1997
UL http://dmd.aspetjournals.org/content/25/1/1.abstract
AB A human UDP-glucuronosyltransferase (UGT) catalyzing the glucuronidation of morphine has been identified. A full length cDNA was isolated from a human liver cDNA library and found to be identical to the UGT2B7 form having a tyrosine at position 268. This cDNA was transfected into HK 293 cells, and stable expression was achieved. Cell homogenates and membrane preparations from HK 293 cells expressing UGT2B7 catalyzed the glucuronidation of morphine and other clinically significant opioid agonists, antagonists, and partial agonists. UGT2B7 catalyzed morphine glucuronidation at the 3- and 6-hydroxy positions and also mediated the formation of codeine-6-glucuronide from codeine. This represents the first demonstration of a UGT capable of catalyzing the glucuronidation of both the 3- and 6-positions of opioids. Since humans excrete morphine-3-glucuronide and morphine-6-glucuronide after morphine administration, it is likely that UGT2B7 is a major isoform in humans responsible for the metabolism of this important drug and its surrogates. The American Society for Pharmacology and Experimental Therapeutics