title: Identifying and applying a highly selective probe to simultaneously determine the O-glucuronidation activity of human UGT1A3 and UGT1A4.
abstract: Glucuronidation mediated by uridine 5'-diphospho (UDP)-glucuronosyltransferase is an important detoxification pathway. However, identifying a selective probe of UDP- glucuronosyltransferase is complicated because of the significant overlapping substrate specificity displayed by the enzyme. In this paper, desacetylcinobufagin (DACB) 3-O- and 16-O-glucuronidation were found to be isoform-specific probe reactions for UGT1A4 and UGT1A3, respectively. DACB was well characterized as a probe for simultaneously determining the catalytic activities of O-glucuronidation mediated by UGT1A3 and UGT1A4 from various enzyme sources, through a sensitive analysis method.
authors.affiliation: College of Pharmacy, Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning, Academy of Integrative Medicine, Dalian Medical University, Dalian, 116044, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: 1] Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China [2] Graduate School of Chinese Academy of Sciences, Beijing, China.
authors.forename: Si-Cheng
authors.initials: SC
authors.lastname: Liang
authors.affiliation: College of Pharmacy, Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning, Academy of Integrative Medicine, Dalian Medical University, Dalian, 116044, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Guang-Bo
authors.initials: GB
authors.lastname: Ge
authors.affiliation: College of Pharmacy, Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning, Academy of Integrative Medicine, Dalian Medical University, Dalian, 116044, China.
authors.forename: Xiao-Kui
authors.initials: XK
authors.lastname: Huo
authors.affiliation: Second Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Qi
authors.affiliation: College of Pharmacy, Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning, Academy of Integrative Medicine, Dalian Medical University, Dalian, 116044, China.
authors.forename: Sa
authors.initials: S
authors.lastname: Deng
authors.affiliation: College of Pharmacy, Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning, Academy of Integrative Medicine, Dalian Medical University, Dalian, 116044, China.
authors.forename: Ke-Xin
authors.initials: KX
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning, Academy of Integrative Medicine, Dalian Medical University, Dalian, 116044, China.
authors.forename: Xiao-Chi
authors.initials: XC
authors.lastname: Ma
mesh_terms: D002018:Bufanolides / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D002018:Bufanolides; D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D011994:Recombinant Proteins; C019787:bilirubin glucuronoside glucuronosyltransferase; C582494:desacetylcinobufagin; C122075:UDP-glucuronosyltransferase, UGT1A3; D014453:Glucuronosyltransferase