葡萄糖醛酸转移酶-药学学报.PDF

药学学报 Acta Pharmaceutica Sinica 2009, 44 ( 11) : 1193 1199 ·1193 · 葡萄糖醛酸转移酶 (UGTs) 诱导羧酸药物代谢激活的研究进展 彤, 梁 艳, 郝海平, 林, 王广基* ( 中国 科大学 物代谢动力学重点实验室, 江苏 南京 210009) 摘要: 含羧酸基团的药物可以通过葡萄糖醛酸转移酶的代谢转化, 形成亲电子活性的酰基葡萄糖醛酸苷活 性中间代谢产物, 然后经过一系列的非酶或酶反应形成蛋白加合物或DNA 加合物。加合物的形成是含羧酸基团 物形成特异质反应和基因毒性的主要因素。本文以该类 物的代谢激活为例, 阐述了酰基葡萄糖醛酸苷的化 学活性、致毒机制、分布特征以及产生的毒性反应, 并探讨了研究现状和前景。 关键词: 羧酸药物; 葡萄糖醛酸转移酶; 酰基葡萄糖醛酸苷; 代谢激活 中图分类号: R969 文献标识码:A 文章编号: 05 13-4870 (2009) 11-1193-07 Advances in study of metabolic activation of carboxyl-acid containing drugs by UGTs * XIE Tong, LIANG Yan, HAO Hai-ping, XIE Lin, WANG Guang-ji (Key Lab of Drug M etabolism and Pharmacokinetics, China Pharmaceutical University, Nanj ing 210009, China) Abstract: The metabolic transformation of the drugs containing carboxylic acid groups can lead to the formation of acyl glucuronide metabolites through catalysis by glucuronosyltransferase, and produce pro-acyl glucuronide intermediate metabolites with electronic activity. Then, protein or DNA adducts appeared after a series of non-enzyme or enzyme reactions. These adducts would change the protein activity and potentially lead to idiosyncratic and genotoxicity. In this paper, we discussed the chemical activity, drug-induced mechanisms, distribution and toxicity resulting from this metabolic activation for these drugs, and stated the status and prospects of research in this field. Key words: carboxyl-acid containing drug;