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Cited by 366Pharmacogenetics and Drug MetabolismGlutathione Transferases and PolymorphismsDrug Transport and Resistance Mechanisms

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

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Riches, Zoe, Stanley, Emma L., Bloomer, Jackie C., Coughtrie, Michael W.H.·2009·Drug Metabolism and Disposition
DOI 10.1124/dmd.109.028399PMC PMC2774979
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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.

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  • Because SULT2A1 expression is mainly limited to the liver, adrenal, colon and kidney, glucuronidation is the more important conjugation reaction in androgen target tissue.

    “As SULT2A1 expression is mainly limited to the liver, adrenal, colon and kidney (Riches et al., 2009), glucuronidation is the more important conjugation reaction in androgen target tissue.”

    From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Riches et al., 2009

  • The liver shows high SULT expression and activity compared to other tissues, including SULT2A1 and SULT2B1 involved in androgen metabolism.

    “The liver also shows high SULT expression and activity compared to other tissues, including SULT2A1 and SULT2B1 involved in androgen metabolism (Meloche and Falany, 2001, Riches et al., 2009).”

    From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Riches et al., 2009

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Authors
Riches, Z., Stanley, E. L., Bloomer, J. C., & Coughtrie, M. W. H.
Affiliations
University of Dundee (GB)
ORCID
Venue
Drug Metabolism and Disposition
Publisher
Elsevier BV
Published
2009-11
Volume
37
Issue
11
Pages
2255-2261
ISSN
0090-9556 (ISSN-L)
DOI
10.1124/dmd.109.028399
PMC
PMC2774979
OpenAlex
W2155462152
Cited by
365
References
51
Citations by year
2026: 10 · 2025: 14 · 2024: 15 · 2023: 18 · 2022: 21 · 2021: 26 · 2020: 19 · 2019: 20 · 2018: 26 · 2017: 33 · 2016: 28 · 2015: 27 · 2014: 31 · 2013: 22 · 2012: 30
FWCI
16.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Drug Metabolism and Disposition (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (publishedVersion)
Funders
Biotechnology and Biological Sciences Research Council (BBS/S/B/2004/11767)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
sulfotransferase, SULT1A1, SULT1A3, SULT1B1, SULT1E1, SULT2A1, sulfation, xenobiotic detoxification, tissue-specific enzyme expression, interindividual variability, enzyme kinetics, human liver, small intestine, kidney, lung, drug metabolism
MeSH terms
Adult, Aged, Enzyme Activation, Female, Humans, Intestine, Small, Isoenzymes, Kidney, Liver, Lung, Male, Middle Aged, Tissue Distribution, Sulfotransferases, Gene Expression Regulation, Enzymologic, Young Adult

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