Coffman B L, Rios G R, King C D, Tephly T R
Department of Pharmacology, University of Iowa, Iowa City 52242, USA.
Drug Metab Dispos. 1997 Jan;25(1):1-4.
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 288. 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.
已鉴定出一种催化吗啡葡萄糖醛酸化的人源UDP - 葡萄糖醛酸基转移酶（UGT）。从人肝脏cDNA文库中分离出一个全长cDNA，发现其与在288位具有酪氨酸的UGT2B7形式相同。将该cDNA转染到HK 293细胞中，并实现了稳定表达。来自表达UGT2B7的HK 293细胞的细胞匀浆和膜制剂催化了吗啡以及其他临床上重要的阿片类激动剂、拮抗剂和部分激动剂的葡萄糖醛酸化。UGT2B7催化吗啡在3 - 和6 - 羟基位置的葡萄糖醛酸化，还介导了可待因形成可待因 - 6 - 葡萄糖醛酸酯。这是首次证明一种UGT能够催化阿片类药物3 - 和6 - 位的葡萄糖醛酸化。由于人类在服用吗啡后会排泄吗啡 - 3 - 葡萄糖醛酸酯和吗啡 - 6 - 葡萄糖醛酸酯，因此UGT2B7很可能是人类中负责这种重要药物及其替代物代谢的主要同工型。
