title: Quantitative regioselectivity of glucuronidation of quercetin by recombinant UDP-glucuronosyltransferases 1A9 and 1A3 using enzymatic kinetic parameters.
abstract: 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.
authors.affiliation: Department of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Y K
authors.initials: YK
authors.lastname: Chen
authors.forename: S Q
authors.initials: SQ
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Zeng
mesh_terms: D003198:Computer Simulation; D020719:Glucuronides / Q000032:analysis / Q000737:chemistry*; D014453:Glucuronosyltransferase / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D007536:Isomerism; D007700:Kinetics; D008956:Models, Chemical; D015202:Protein Engineering / Q000379:methods*; D011794:Quercetin / Q000032:analysis / Q000737:chemistry*; D011994:Recombinant Proteins / Q000032:analysis / Q000737:chemistry; D000090264:UDP-Glucuronosyltransferase 1A9
chemical_list: D020719:Glucuronides; D011994:Recombinant Proteins; D011794:Quercetin; C122075:UDP-glucuronosyltransferase, UGT1A3; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9