Ebner T, Burchell B
Department of Biochemical Medicine, University of Dundee, Scotland, UK.
Drug Metab Dispos. 1993 Jan-Feb;21(1):50-5.
Two cloned human hepatic UDP-glucuronosyltransferase (UGT) cDNAs were stably expressed in chinese hamster V79 cells. More than 100 drugs and xenobiotics were used as substrates for glucuronidation catalyzed by the cloned human transferases to determine the chemical structures accepted as substrates. UGT HP1 exhibited a limited substrate specificity for planar phenolic compounds, whereas UGT HP4 was more promiscuous in acceptance of non-planar phenols, anthraquinones, flavones, aliphatic alcohols, aromatic carboxylic acids, steroids, and many drugs of varied structure. Levels of HP4 UGT activity toward some substrates were sufficient to allow determination of kinetic parameters for the enzyme reaction. Metabolism of drugs could be studied by addition to the recombinant cell lines in culture, and extraction of the media allowed analysis of glucuronide formation. Data presented herein demonstrate the potential of using these recombinant cell lines for investigation of phase II metabolism by human UGTs.
两个克隆的人肝UDP - 葡萄糖醛酸基转移酶（UGT）cDNA在中华仓鼠V79细胞中稳定表达。超过100种药物和外源性物质被用作克隆的人转移酶催化葡萄糖醛酸化的底物，以确定被接受为底物的化学结构。UGT HP1对平面酚类化合物表现出有限的底物特异性，而UGT HP4在接受非平面酚类、蒽醌、黄酮、脂肪醇、芳香羧酸、类固醇以及许多结构各异的药物方面更为广泛。HP4 UGT对某些底物的活性水平足以测定酶反应的动力学参数。通过向培养的重组细胞系中添加药物来研究药物代谢，并通过提取培养基来分析葡萄糖醛酸苷的形成。本文提供的数据证明了使用这些重组细胞系研究人UGT介导的II相代谢的潜力。
