Human Cytosolic Sulfotransferase SULT1A3 Mediates the Sulfation of Dextrorphan

  • Yamamoto Akihiro
    Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki
  • Kurogi Katsuhisa
    Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki
  • Schiefer Isaac Thomas
    Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus
  • Liu Ming-Yih
    National Synchrotron Radiation Research Center
  • Sakakibara Yoichi
    Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki
  • Suiko Masahito
    Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki
  • Liu Ming-Cheh
    Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus

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<p>Dextrorphan, an active metabolite of the antitussive dextromethorphan, has been shown to be subjected to sulfation by several zebrafish cytosolic sulfotransferases (SULTs). We were interested in finding out which of the human SULT(s) is(are) capable of catalyzing the sulfation of dextrorphan, and to verify whether sulfation of dextrorphan may occur in cultured human cells and human organ cytosols. Data from the enzymatic assays showed that, of all thirteen known human SULTs, SULT1A3 displayed the strongest dextrorphan-sulfating activity. Cell culture experiments using HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells incubated with [35S]sulfate together with varying concentrations of dextrorphan revealed indeed the production and release of [35S]sulfated dextrorphan in a concentration-dependent manner. Additionally, significant dextrorphan-sulfating activity was detected in human liver, small intestine and lung cytosols. Taken together, these results provided a biochemical basis for the sulfation of dextrorphan in humans.</p>

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