Noort D, Coughtrie M W, Burchell B, van der Marel G A, van Boom J H, van der Gen A, Mulder G J
Division of Toxicology, University of Leiden, The Netherlands.
Eur J Biochem. 1990 Mar 10;188(2):309-12. doi: 10.1111/j.1432-1033.1990.tb15404.x.
A series of possible transition state analogues of the glucuronidation reaction catalyzed by UDP-glucuronosyltransferase were tested for their inhibitory effect on glucuronidation of various substrates in a rat liver microsomal fraction. In general 4-nitrophenol glucuronidation was more effectively inhibited than that of 1-naphthol, bilirubin or testosterone. 2-(1-Naphthyl)ethyl-UDP and 2,2,2-(triphenyl)ethyl-UDP were the most effective inhibitors. Their inhibitory effect was competitive towards both UDP-glucuronic acid and 4-nitrophenol. These compounds were much more effective inhibitors than UDP; therefore addition of a lipophilic group enhances the inhibitory potency of UDP. The various UDP derivatives showed differences in their abilities to inhibit the glucuronidation of the four acceptor substrates, supporting the concept that the different forms of UDP-glucuronosyl transferase have different active sites.
对一系列可能作为尿苷二磷酸葡萄糖醛酸基转移酶催化的葡萄糖醛酸化反应过渡态类似物，测试了它们对大鼠肝微粒体组分中各种底物葡萄糖醛酸化的抑制作用。一般来说，4-硝基苯酚的葡萄糖醛酸化比1-萘酚、胆红素或睾酮的葡萄糖醛酸化更易被抑制。2-(1-萘基)乙基-尿苷二磷酸和2,2,2-(三苯基)乙基-尿苷二磷酸是最有效的抑制剂。它们的抑制作用对尿苷二磷酸葡萄糖醛酸和4-硝基苯酚均呈竞争性。这些化合物作为抑制剂比尿苷二磷酸有效得多；因此，添加亲脂性基团可增强尿苷二磷酸的抑制效力。各种尿苷二磷酸衍生物在抑制四种受体底物葡萄糖醛酸化的能力上存在差异，这支持了不同形式的尿苷二磷酸葡萄糖醛酸基转移酶具有不同活性位点的观点。
