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Identification and Characterization of the Human Cytosolic Sulfotransferases Mediating the Sulfation of Clioquinol and Iodoquinol

Identification and Characterization of the Human Cytosolic Sulfotransferases Mediating the Sulfation of Clioquinol and Iodoquinol

Akihiro Yamamoto, Maame Debrah-Pinamang, Nicholas J DiModica, Katsuhisa Kurogi, Ali A Naqvi, Ying Hui, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu

Drug Metab Lett. 2016;10(3):200-205.

PMID: 27449410

Abstract:

Objective:
The aim of the current study was to identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating clioquinol and iodoquinol, and to verify the presence of clioquinol/ iodoquinol-sulfating activity in human organ homogenates and cultured cells.
Method:
An established sulfotransferase assay was employed to analyze clioquinol/iodoquinolsulfating activity of thirteen known human SULTs, as well as cytosols of human kidney, liver, lung, and small intestine. Metabolic labeling with [35S]sulfate in the presence of different concentrations of clioquinol/iodoquinol was performed using cultured HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells.
Results:
A systematic analysis revealed that six of the thirteen known human SULTs, SULT1A1 SULT1A2, SULTA3, SULT1B1, SULT1C4, and SULT1E1 showed considerable clioquinol/ iodoquinol-sulfating activity. Kinetic parameters of the sulfation of clioquinol and iodoquinol by three SULTs, SULT1A1, SULT1A3, and SULT1C4, that showed the strongest clioquinol/iodoquinolsulfating activity were determined. Moreover, clioquinol/iodoquinol-sulfating activity was detected in the cytosol fractions of human liver, lung, kidney, and small intestine. Cultured HepG2 and Caco-2 cells were shown to be capable of sulfating clioquinol/iodoquinol under metabolic conditions.
Conclusion:
Collectively, these results provided a molecular basis underling the metabolism of clioquinol and iodoquinol through sulfation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP83738	Iodoquinol		83-73-8	Price

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