DICP OpenIR
UGT1A10 Is a High Activity and Important Extrahepatic Enzyme: Why Has Its Role in Intestinal Glucuronidation Been Frequently Underestimated?
Troberg, Johanna1; Jarvinen, Erkka1; Ge, Guang-Bo2; Yang, Ling2; Finel, Moshe1
KeywordUdp-glucuronosyltransferase Recombinant Ugt1a10 Intestine Microsomes Intestinal Glucuronidation Estradiol Estrone Morphine Sn-38 Amc Nchn Bavachinin
Source PublicationMOLECULAR PHARMACEUTICS
2017-09-01
DOI10.1021/acs.molpharmaceut.6b00852
Volume14Issue:9Pages:2875-2883
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS KeywordHUMAN UDP-GLUCURONOSYLTRANSFERASES ; TANDEM MASS-SPECTROMETRY ; TRANSFERASE 1A ; HUMAN TISSUES ; UGT ENZYMES ; IN-VITRO ; EXPRESSION ; ISOFORMS ; QUANTIFICATION ; SELECTIVITY
AbstractThe 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.
Language英语
WOS IDWOS:000410005100003
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/150036
Collection中国科学院大连化学物理研究所
Affiliation1.Univ Helsinki, Div Pharmaceut Chem & Technol, Fac Pharm, POB 56 Viikinkaari 5, Helsinki 00014, Finland
2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
Recommended Citation
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.
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