Wooster R, Ebner T, Sutherland L, Clarke D, Burchell B
Department of Biochemical Medicine, Ninewells Hospital Medical School, Scotland, UK.
Toxicology. 1993 Oct 5;82(1-3):119-29. doi: 10.1016/0300-483x(93)02607-i.
Two human UDP-Glucuronosyltransferase (UGT) cDNA clones were stably integrated into V79 chinese hamster fibroblast cells and the functional enzymes were expressed in this heterologous environment. More than 100 drugs and xenobiotics were used as substrates for glucuronidation, catalysed by the cloned UGTs to determine the chemical structures accepted as substrates. UGT HP1 exhibited a limited 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. These conclusions are illustrated here by using a series of alkyl- and halophenols. This work indicates the considerable potential value in use of these recombinant cell lines to study human drug glucuronidation.
两个人类尿苷二磷酸葡萄糖醛酸基转移酶（UGT）cDNA克隆被稳定整合到V79中国仓鼠成纤维细胞中，并且功能性酶在这种异源环境中得以表达。超过100种药物和外源性物质被用作葡萄糖醛酸化的底物，由克隆的UGT催化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宽泛。这里通过使用一系列烷基酚和卤代酚来说明这些结论。这项工作表明使用这些重组细胞系来研究人类药物葡萄糖醛酸化具有相当大的潜在价值。
