Quantitative regioselectivity of glucuronidation of quercetin by recombinant UDP-glucuronosyltransferases 1A9 and 1A3 using enzymatic kinetic parameters
Quantitative regioselectivity of glucuronidation of quercetin by recombinant UDP-glucuronosyltransferases 1A9 and 1A3 using enzymatic kinetic parameters
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DOI：
10.1080/00498250500372172
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发表时间：
2005-10-01
期刊：
影响因子：
1.8
通讯作者：
Zeng, S
中科院分区：
文献类型：
--
作者：
Chen, YK;Chen, SQ;Zeng, S
槲皮素已被认为至少部分地通过其代谢产物如葡萄糖醛酸苷发挥其药理作用。定量区域选择性分析对于了解UDP-葡萄糖醛酸转移酶（UGT）对槲皮素药理活性的贡献非常重要。本工作通过Bac-to-Bac表达系统获得了活性UGT 1A 9和UGT 1A 3酶，并且槲皮素被它们各自代谢为四种单葡萄糖醛酸苷（7-、3-、4 '-和3'-葡萄糖醛酸苷）。计算每种葡糖苷酸的酶动力学参数，以定量阐明UGT 1A 9和UGT 1A 3对槲皮素的区域选择性。观察到UGT 1A 3对3 '-葡萄糖醛酸苷的葡萄糖醛酸化效率最高，其次是3-、4'-和7-葡萄糖醛酸苷。UGT 1A 9的催化效率顺序为3- > 7- > 3 '-> 4'-葡糖苷酸。
Quercetin has been suggested to exert its pharmacological effects, at least in part, via its metabolites, such as glucuronides. Quantitative regioselectivity analyses are important to understand the contributions of UDP-glucuronosyltransferases (UGTs) to the pharmacological activity of quercetin. The present work obtained active UGT1A9 and UGT1A3 enzymes with a Bac-to-Bac expression system, and quercetin was metabolized by each of them to four monoglucuronides (7-, 3-, 4'- and 3'-glucuronide). Enzymatic kinetic parameters of each glucuronide were calculated to elucidate quantitatively UGT1A9's and UGT1A3's regioselectivities for quercetin. UGT1A3's highest glucuronidation efficiency was observed for the 3'-glucuronide, then the 3-, 4'- and 7-glucuronide. The catalytic efficiency order for UGT1A9 was 3- > 7- > 3'- > 4'-glucuronide.