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.