UGT1A10 Is a High Activity and Important Extrahepatic Enzyme: Why Has Its Role in Intestinal Glucuronidation Been Frequently Underestimated?

	UGT1A10 Is a High Activity and Important Extrahepatic Enzyme: Why Has Its Role in Intestinal Glucuronidation Been Frequently Underestimated?
	Troberg, Johanna 2; Jarvinen, Erkka 2; Ge, Guang-Bo 1; Yang, Ling 1; Finel, Moshe 2
刊名	MOLECULAR PHARMACEUTICS
	2017-09-01
卷号	14 期号:9 页码:2875-2883
关键词	UDP-glucuronosyltransferase recombinant UGT1A10 intestine microsomes intestinal glucuronidation estradiol estrone morphine SN-38 AMC NCHN bavachinin
英文摘要	The aim of this work was to highlight a considerable and broad problem in UGT1A10 activity assessment that has led to underestimation of its role in intestinal glucuronidation of drugs and other xenobiotics. The reason appears to be poor activity of the commercial UGT1A10 that is used by many laboratories, and here we have tested it by comparison with our recombinant His-tagged UGT1A10 (designated as UGT1A10-H), both expressed in insect cells. The glucuronidation rates of morphine, estradiol, estrone, SN-38, diclofenac, 4-methylumbelliferone, 7-amino-4-methylcoumarin, N-(3-carboxypropyl)-4-hydroxy-1,8-naphthalimide, and bavachinin were assayed. The results revealed that the activity of commercial UGT1A10 was low, very low, and in the cases of morphine, estrone, 7-methyl-4-aminocoumarin, and bavachinin it was below the detection limit. On the other hand, under the same conditions, UGT1A10-H exhibited high glucuronidation rates toward all these compounds. Moreover, using estradiol, morphine, and estrone, in the presence and absence of suitable inhibitors, nilotinib or atractylenolide I, it was demonstrated that UGT1A10-H, but not the commercial UGT1A10, provides a good tool to study the role of native UGT1A10 in the human intestine. The results also suggest that much of the data in the literature on UGT1A10 activity may have to be re-evaluated.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]	Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]	HUMAN UDP-GLUCURONOSYLTRANSFERASES ; TANDEM MASS-SPECTROMETRY ; TRANSFERASE 1A ; HUMAN TISSUES ; UGT ENZYMES ; IN-VITRO ; EXPRESSION ; ISOFORMS ; QUANTIFICATION ; SELECTIVITY
收录类别	SCI
语种	英语
WOS记录号	WOS:000410005100003
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/150136]
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.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China 2.Univ Helsinki, Div Pharmaceut Chem & Technol, Fac Pharm, POB 56 Viikinkaari 5, Helsinki 00014, Finland
推荐引用方式 GB/T 7714	Troberg, Johanna,Jarvinen, Erkka,Ge, Guang-Bo,et al. UGT1A10 Is a High Activity and Important Extrahepatic Enzyme: Why Has Its Role in Intestinal Glucuronidation Been Frequently Underestimated?[J]. MOLECULAR PHARMACEUTICS,2017,14(9):2875-2883.
APA	Troberg, Johanna,Jarvinen, Erkka,Ge, Guang-Bo,Yang, Ling,&Finel, Moshe.(2017).UGT1A10 Is a High Activity and Important Extrahepatic Enzyme: Why Has Its Role in Intestinal Glucuronidation Been Frequently Underestimated?.MOLECULAR PHARMACEUTICS,14(9),2875-2883.
MLA	Troberg, Johanna,et al."UGT1A10 Is a High Activity and Important Extrahepatic Enzyme: Why Has Its Role in Intestinal Glucuronidation Been Frequently Underestimated?".MOLECULAR PHARMACEUTICS 14.9(2017):2875-2883.