Glucuronidation of bavachinin by human tissues and expressed UGT enzymes: Identification of UGT1A1 and UGT1A8 as the major contributing enzymes

	Glucuronidation of bavachinin by human tissues and expressed UGT enzymes: Identification of UGT1A1 and UGT1A8 as the major contributing enzymes
	Lv, Xia 1,2; Hou, Jie 3; Xia, Yang-Liu 2; Ning, Jing 2,3; He, Gui-Yuan 2; Wang, Ping 2; Ge, Guang-Bo 2; Xiu, Zhi-Long 1; Yang, Ling 2
刊名	drug metabolism and pharmacokinetics
	2015-10-01
卷号	30 期号:5 页码:358-365
关键词	Bavachinin UDP-glucuronosyltransferases UGT1A1 UGT1A8 Glucuronidation Human tissues
英文摘要	bavachinin (bci), a major bioactive compound in chinese herbal psoralea corylifolia, possesses a wide range of biological activities. in this study, the glucuronidation pathway of bci was characterized for the first time, by using pooled human liver microsomes (hlm), pooled human intestine microsomes (him) and recombinant human udp-glucosyltransferases (ugts). one mono-glucuronide was detected in hlm in the presence of uridine-diphosphate glucuronic acid (udpga), and it was biosynthesized and well-characterized as bci-4'-o-glucuronide (bcig). reaction phenotyping assay showed that ugt1a1, ugt1a3 and ugt1a8 were involved in bci-4'-o-glucuronidation, while ugt1a1 and ugt1a8 displayed the higher catalytic ability among all tested ugt isoforms. kinetic analysis demonstrated that bci-4'-o-glucuronidation in both hlm and ugt1a1 followed sigmoidal kinetic behaviors and displayed much close km values (12.4 mu m in hlm & 9.7 mu m in ugt1a1). both chemical inhibition assays and correlation analysis demonstrated that ugt1a1 displayed a predominant role in bci-4'-o-glucuronidation in hlm. both him and ugt1a8 exhibited substrate inhibition at high concentrations, and km values of him and ugt1a8 were 3.6 and 2.3 mm, respectively. similar catalytic efficiencies were observed for him (199.3 mu l/min/mg) and ugt1a8 (216.2 ml/min/mg). these findings suggested that ugt1a1 and ugt1a8 were the primary isoforms involved in bci-4'-o-glucuronidation in hlm, and him, respectively. copyright (c) 2015, the japanese society for the study of xenobiotics. published by elsevier ltd. all rights reserved.
WOS标题词	science & technology ; life sciences & biomedicine
类目[WOS]	pharmacology & pharmacy
研究领域[WOS]	pharmacology & pharmacy
关键词[WOS]	udp-glucuronosyltransferase isoforms ; human liver ; psoralea-corylifolia ; in-vitro ; liquid-chromatography ; acid ; intestine ; magnolol ; potent ; seeds
收录类别	SCI
语种	英语
WOS记录号	WOS:000362974900006
公开日期	2016-05-09
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/146597]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
作者单位	1.Dalian Univ Technol, Dept Biosci & Biotechnol, Dalian, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China 3.Dalian Med Univ, Dalian, Peoples R China
推荐引用方式 GB/T 7714	Lv, Xia,Hou, Jie,Xia, Yang-Liu,et al. Glucuronidation of bavachinin by human tissues and expressed UGT enzymes: Identification of UGT1A1 and UGT1A8 as the major contributing enzymes[J]. drug metabolism and pharmacokinetics,2015,30(5):358-365.
APA	Lv, Xia.,Hou, Jie.,Xia, Yang-Liu.,Ning, Jing.,He, Gui-Yuan.,...&Yang, Ling.(2015).Glucuronidation of bavachinin by human tissues and expressed UGT enzymes: Identification of UGT1A1 and UGT1A8 as the major contributing enzymes.drug metabolism and pharmacokinetics,30(5),358-365.
MLA	Lv, Xia,et al."Glucuronidation of bavachinin by human tissues and expressed UGT enzymes: Identification of UGT1A1 and UGT1A8 as the major contributing enzymes".drug metabolism and pharmacokinetics 30.5(2015):358-365.