title: Sulphation of acetaminophen by the human cytosolic sulfotransferases: a systematic analysis.
abstract: Sulphation is known to be critically involved in the metabolism of acetaminophen in vivo. This study aimed to systematically identify the major human cytosolic sulfotransferase (SULT) enzyme(s) responsible for the sulphation of acetaminophen. A systematic analysis showed that three of the twelve human SULTs, SULT1A1, SULT1A3 and SULT1C4, displayed the strongest sulphating activity towards acetaminophen. The pH dependence of the sulphation of acetaminophen by each of these three SULTs was examined. Kinetic parameters of these three SULTs in catalysing acetaminophen sulphation were determined. Moreover, sulphation of acetaminophen was shown to occur in HepG2 human hepatoma cells and Caco-2 human intestinal epithelial cells under the metabolic setting. Of the four human organ samples tested, liver and intestine cytosols displayed considerably higher acetaminophen-sulphating activity than those of lung and kidney. Collectively, these results provided useful information concerning the biochemical basis underlying the metabolism of acetaminophen in vivo previously reported.
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614, USA; Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan; and.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan.
authors.forename: Ming-Yih
authors.initials: MY
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614, USA; Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan; and.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Kurogi
authors.affiliation: Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan; and.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakakibara
authors.affiliation: Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan; and.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Saeki
authors.affiliation: Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan; and.
authors.forename: Masahito
authors.initials: M
authors.lastname: Suiko
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614, USA; ming.liu@utoledo.edu.
authors.forename: Ming-Cheh
authors.initials: MC
authors.lastname: Liu
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics*; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics*; D015239:Arylsulfotransferase / Q000378:metabolism*; D055162:Biocatalysis; D018938:Caco-2 Cells; D003600:Cytosol / Q000201:enzymology*; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D015238:Sulfotransferases / Q000378:metabolism*
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; C513319:SULT1C2 protein, human; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C403170:monoamine-sulfating phenol sulfotransferase
keywords: SULT; acetaminophen; cytosolic sulfotransferase; sulfation