title: Quantitative evaluation of the expression and activity of five major sulfotransferases (SULTs) in human tissues: the SULT "pie".
abstract: Expression levels of the major human sulfotransferases (SULTs) involved in xenobiotic detoxification in a range of human tissues (i.e., SULT "pies") are not available in a form allowing comparison between tissues and individuals. Here we have determined, by quantitative immunoblotting, expression levels for the five principal human SULTs-SULT1A1, SULT1A3/4, SULT1B1, SULT1E1, and SULT2A1-and determined the kinetic properties toward probe substrates, where available, for these enzymes in cytosol samples from a bank of adult human liver, small intestine, kidney, and lung. We produced new isoform-selective antibodies against SULT1B1 and SULT2A1, which were used alongside antibodies against SULT1A3 and SULT1A1 previously produced in our laboratory or available commercially (SULT1E1). Expression levels were derived using purified recombinant enzymes to construct standard curves for each individual isoform and immunoblot. Substantial intertissue and interindividual differences in expression were observed. SULT1A1 was the major enzyme (>50% of total, range 420-4900 ng/mg cytosol protein) in the liver, followed by SULT2A1, SULT1B1, and SULT1E1. SULT1A3 was completely absent from this tissue. In contrast, the small intestine contained the largest overall amount of SULT of any of the tissues, with SULT1B1 the major enzyme (36%), closely followed by SULT1A3 (31%), and SULT1A1, SULT1E1, and SULT2A1 more minor forms (19, 8, and 6% of total, respectively). The kidney and lung contained low levels of SULT. We provide a unique data set that will add value to the study of the role and contribution of sulfation to drug and xenobiotic metabolism in humans.
authors.affiliation: Division of Medical Sciences, Centre for Oncology and Molecular Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Riches
authors.forename: Emma L
authors.initials: EL
authors.lastname: Stanley
authors.forename: Jackie C
authors.initials: JC
authors.lastname: Bloomer
authors.forename: Michael W H
authors.initials: MW
authors.lastname: Coughtrie
mesh_terms: D000328:Adult; D000368:Aged; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007421:Intestine, Small / Q000737:chemistry / Q000201:enzymology; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000737:chemistry / Q000201:enzymology; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008168:Lung / Q000737:chemistry / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D015238:Sulfotransferases / Q000032:analysis* / Q000096:biosynthesis* / Q000235:genetics; D014018:Tissue Distribution / Q000502:physiology; D055815:Young Adult
chemical_list: D007527:Isoenzymes; D015238:Sulfotransferases
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