Ethanol sulfation by the human cytosolic sulfotransferases: a systematic analysis.

Ethyl sulfate, a minor and direct ethanol metabolite in adult human body, has been implicated as a biomarker for alcohol consumption and in utero exposure to ethanol. To understand better the physiological relevance of the sulfation of ethanol, it is important to clarify the cytosolic sulfotransferase (SULT) enzymes that are responsible for ethanol sulfation. The present study aimed to identify the major ethanol-sulfating human SULTs and to investigate the sulfation of ethanol under the metabolic setting. A systematic analysis revealed four ethanol-sulfating SULTs, SULT1A1, SULT1A2, SULT1A3, and SULT1C4, among the eleven human SULT enzymes previously prepared and purified. A metabolic labeling study demonstrated the generation and release of ethyl [(35)S]sulfate in a concentration-dependent manner by HepG2 human hepatoma cells labeled with [(35)S]sulfate in the presence of different concentrations of ethanol. Cytosol or S9 fractions of human lung, liver, and small intestine were examined to verify the presence of ethanol-sulfating activity in vivo. Of the three human organs, the small intestine displayed the highest activity.

Sulfation of ractopamine and salbutamol by the human cytosolic sulfotransferases.

Feed additives such as ractopamine and salbutamol are pharmacologically active compounds, acting primarily as ß-adrenergic agonists. This study was designed to investigate whether the sulfation of ractopamine and salbutamol may occur under the metabolic conditions and to identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating two major feed additive compounds, ractopamine and salbutamol. A metabolic labelling study showed the generation and release of [(35)S]sulfated ractopamine and salbutamol by HepG2 human hepatoma cells labelled with [(35)S]sulfate in the presence of these two compounds. A systematic analysis using 11 purified human SULTs revealed SULT1A3 as the major SULT responsible for the sulfation of ractopamine and salbutamol. The pH dependence and kinetic parameters were analyzed. Moreover, the inhibitory effects of ractopamine and salbutamol on SULT1A3-mediated dopamine sulfation were investigated. Cytosol or S9 fractions of human lung, liver, kidney and small intestine were examined to verify the presence of ractopamine-/salbutamol-sulfating activity in vivo. Of the four human organs, the small intestine displayed the highest activity towards both compounds. Collectively, these results imply that the sulfation mediated by SULT1A3 may play an important role in the metabolism and detoxification of ractopamine and salbutamol.