Quantitative evaluation of the expression and activity of five major sulfotransferases (SULTs) in human tissues: the SULT "pie"

TitleQuantitative evaluation of the expression and activity of five major sulfotransferases (SULTs) in human tissues: the SULT "pie"
Publication TypeJournal Article
Year of Publication2009
AuthorsRiches Z, Stanley EL, Bloomer JC, Coughtrie MWH
JournalDrug Metab Dispos
Volume37
Issue11
Pagination2255-61
Date Published11/2009
ISSN1521-009X
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.

DOI10.1124/dmd.109.028399
Alternate JournalDrug Metab. Dispos.
PubMed ID19679676
PubMed Central IDPMC2774979
Grant ListBBS/S/B/2004/11767 / / Biotechnology and Biological Sciences Research Council / United Kingdom
G0000267 / / Medical Research Council / United Kingdom
G0000281 / / Medical Research Council / United Kingdom