| Human UDP-glucuronosyltransferase isoforms involved in bisphenol A glucuronidation. | |
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MedLine Citation:
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PMID: 18990428 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bisphenol A (BPA) is one of a number of potential endocrine disruptors which may affect normal hormonal function. In this study, human UDP-glucuronosyltransferase (UGT) isoforms involved in BPA glucuronidation were studied by kinetic analyses using human liver microsomes and recombinant human UGTs expressed in insect cells (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17). BPA glucuronidation was catalyzed by UGT1A1, UGT1A3, UGT1A9, UGT2B4, UGT2B7 and UGT2B15 as well as by human liver microsomes. Among these UGTs, UGT2B15 showed the highest activity of BPA glucuronidation at low- (1.0 microM) and high- (20 microM) substrate concentrations. Kinetic analyses of BPA glucuronidation were performed by constructing Michaelis-Menten and Eadie-Hofstee plots. The kinetic profile of BPA glucuronidation by pooled human liver microsomes and UGT2B15 was monophasic, the K(m) and V(max) values were 6.39 microM and 4250 pmol min(-1)mg(-1)protein for pooled human liver microsomes, and 8.68 microM and 873 pmol min(-1)mg(-1)protein for UGT2B15, respectively. The K(m) values for BPA glucuronidation by pooled human liver microsomes and UGT2B15 were similar. These findings demonstrate that BPA is mainly glucuronidated by UGT2B15 in human liver microsomes, and suggest that this UGT isoform plays important roles in the detoxification and elimination of BPA. |
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Authors:
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Nobumitsu Hanioka; Takanori Naito; Shizuo Narimatsu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-11-05 |
Journal Detail:
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Title: Chemosphere Volume: 74 ISSN: 1879-1298 ISO Abbreviation: Chemosphere Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-17 Completed Date: 2009-01-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0320657 Medline TA: Chemosphere Country: England |
Other Details:
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Languages: eng Pagination: 33-6 Citation Subset: IM |
Affiliation:
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Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Animals Cell Line Chromatography, High Pressure Liquid Chromatography, Thin Layer Female Glucuronides / chemistry, metabolism* Glucuronosyltransferase / genetics, metabolism* Humans Isoenzymes / genetics, metabolism Kinetics Male Microsomes, Liver / metabolism Middle Aged Phenols / chemistry, metabolism* Recombinant Proteins / metabolism Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Glucuronides; 0/Isoenzymes; 0/Phenols; 0/Recombinant Proteins; 80-05-7/bisphenol A; EC 2.4.1.17/Glucuronosyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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