Human UGT2B7 catalyzes morphine glucuronidation.
Human UGT2B7 catalyzes morphine glucuronidation.
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发表时间：
1997
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通讯作者：
B. Coffman;G. Rios;C. King;T. Tephly
中科院分区：
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作者：
B. Coffman;G. Rios;C. King;T. Tephly
已鉴定了催化吗啡葡萄糖醛酸化的人UDP-葡萄糖醛酸基转移酶（UGT）。从人肝cDNA文库中分离全长cDNA，发现其与在288位具有酪氨酸的UGT 2B 7形式相同。将该cDNA转染HK 293细胞，获得稳定表达.来自表达UGT 2B 7的HK 293细胞的细胞匀浆和膜制备物催化吗啡和其他具有临床意义的阿片激动剂、拮抗剂和部分激动剂的葡萄糖醛酸化。UGT 2B 7在3-和6-羟基位置催化吗啡葡萄糖醛酸化，还介导可待因形成可待因-6-葡萄糖醛酸苷。这代表了UGT能够催化阿片类药物的3位和6位的葡萄糖醛酸化的首次证明。由于人类在吗啡给药后排泄吗啡-3-葡萄糖醛酸苷和吗啡-6-葡萄糖醛酸苷，因此UGT 2B 7可能是人体中负责这种重要药物及其替代物代谢的主要亚型。
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.