Human UDP-glucuronosyltransferase isoforms involved in bisphenol A glucuronidation

Nobumitsu Hanioka; Takanori Naito; Shizuo Narimatsu

doi:10.1016/j.chemosphere.2008.09.053

Human UDP-glucuronosyltransferase isoforms involved in bisphenol A glucuronidation

Nobumitsu Hanioka, Takanori Naito, Shizuo Narimatsu

Research output: Contribution to journal › Article › peer-review

98 Citations (Scopus)

Abstract

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 μM) and high- (20 μM) 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 μM and 4250 pmol min^-1 mg^-1 protein for pooled human liver microsomes, and 8.68 μM 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.

Original language	English
Pages (from-to)	33-36
Number of pages	4
Journal	Chemosphere
Volume	74
Issue number	1
DOIs	https://doi.org/10.1016/j.chemosphere.2008.09.053
Publication status	Published - Dec 2008
Externally published	Yes

Keywords

Bisphenol
Human liver microsomes
UDP-glucuronosyltransferase
UGT2B15

ASJC Scopus subject areas

Environmental Engineering
Chemistry(all)
Environmental Chemistry
Pollution
Public Health, Environmental and Occupational Health
Health, Toxicology and Mutagenesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chemosphere.2008.09.053

Cite this

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title = "Human UDP-glucuronosyltransferase isoforms involved in bisphenol A glucuronidation",

abstract = "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 μM) and high- (20 μM) 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 Km and Vmax values were 6.39 μM and 4250 pmol min-1 mg-1 protein for pooled human liver microsomes, and 8.68 μM and 873 pmol min-1 mg-1 protein for UGT2B15, respectively. The Km 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.",

keywords = "Bisphenol, Human liver microsomes, UDP-glucuronosyltransferase, UGT2B15",

author = "Nobumitsu Hanioka and Takanori Naito and Shizuo Narimatsu",

note = "Funding Information: This work was supported in part by a Grant-in-Aid for Scientific Research (20590121) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.",

year = "2008",

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T1 - Human UDP-glucuronosyltransferase isoforms involved in bisphenol A glucuronidation

AU - Hanioka, Nobumitsu

AU - Naito, Takanori

AU - Narimatsu, Shizuo

N1 - Funding Information: This work was supported in part by a Grant-in-Aid for Scientific Research (20590121) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

PY - 2008/12

Y1 - 2008/12

N2 - 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 μM) and high- (20 μM) 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 Km and Vmax values were 6.39 μM and 4250 pmol min-1 mg-1 protein for pooled human liver microsomes, and 8.68 μM and 873 pmol min-1 mg-1 protein for UGT2B15, respectively. The Km 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.

AB - 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 μM) and high- (20 μM) 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 Km and Vmax values were 6.39 μM and 4250 pmol min-1 mg-1 protein for pooled human liver microsomes, and 8.68 μM and 873 pmol min-1 mg-1 protein for UGT2B15, respectively. The Km 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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KW - Human liver microsomes

KW - UDP-glucuronosyltransferase

KW - UGT2B15

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Human UDP-glucuronosyltransferase isoforms involved in bisphenol A glucuronidation

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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