Human sulfotransferases and their role in chemical metabolism

Niranjali Gamage, Amanda Barnett, Nadine Hempel, Ronald G. Duggleby, Kelly F. Windmill, Jennifer L. Martin, Michael E. McManus

Research output: Contribution to journalReview article

373 Citations (Scopus)

Abstract

Sulfonation is an important reaction in the metabolism of numerous xenobiotics, drugs, and endogenous compounds. A supergene family of enzymes called sulfotransferases (SULTs) catalyze this reaction. In most cases, the addition of a sulfonate moiety to a compound increases its water solubility and decreases its biological activity. However, many of these enzymes are also capable of bioactivating procarcinogens to reactive electrophiles. In humans three SULT families, SULT1, SULT2, and SULT4, have been identified that contain at least thirteen distinct members. SULTs have a wide tissue distribution and act as a major detoxification enzyme system in adult and the developing human fetus. Nine crystal structures of human cytosolic SULTs have now been determined, and together with site-directed mutagenesis experiments and molecular modeling, we are now beginning to understand the factors that govern distinct but overlapping substrate specificities. These studies have also provided insight into the enzyme kinetics and inhibition characteristics of these enzymes. The regulation of human SULTs remains as one of the least explored areas of research in the field, though there have been some recent advances on the molecular transcription mechanism controlling the individual SULT promoters. Interindividual variation in sulfonation capacity may be important in determining an individual's response to xenobiotics, and recent studies have begun to suggest roles for SULT polymorphism in disease susceptibility. This review aims to provide a summary of our present understanding of the function of human cytosolic sulfotransferases.

Original languageEnglish (US)
Pages (from-to)5-22
Number of pages18
JournalToxicological Sciences
Volume90
Issue number1
DOIs
StatePublished - Mar 1 2006

Fingerprint

Sulfotransferases
Metabolism
Enzymes
Sulfonation
Xenobiotics
Enzyme inhibition
Enzyme kinetics
Detoxification
Mutagenesis
Molecular modeling
Disease Susceptibility
Tissue Distribution
Transcription
Substrate Specificity
Site-Directed Mutagenesis
Bioactivity
Polymorphism
Solubility
Fetus
Crystal structure

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Gamage, N., Barnett, A., Hempel, N., Duggleby, R. G., Windmill, K. F., Martin, J. L., & McManus, M. E. (2006). Human sulfotransferases and their role in chemical metabolism. Toxicological Sciences, 90(1), 5-22. https://doi.org/10.1093/toxsci/kfj061
Gamage, Niranjali ; Barnett, Amanda ; Hempel, Nadine ; Duggleby, Ronald G. ; Windmill, Kelly F. ; Martin, Jennifer L. ; McManus, Michael E. / Human sulfotransferases and their role in chemical metabolism. In: Toxicological Sciences. 2006 ; Vol. 90, No. 1. pp. 5-22.
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Gamage, N, Barnett, A, Hempel, N, Duggleby, RG, Windmill, KF, Martin, JL & McManus, ME 2006, 'Human sulfotransferases and their role in chemical metabolism', Toxicological Sciences, vol. 90, no. 1, pp. 5-22. https://doi.org/10.1093/toxsci/kfj061

Human sulfotransferases and their role in chemical metabolism. / Gamage, Niranjali; Barnett, Amanda; Hempel, Nadine; Duggleby, Ronald G.; Windmill, Kelly F.; Martin, Jennifer L.; McManus, Michael E.

In: Toxicological Sciences, Vol. 90, No. 1, 01.03.2006, p. 5-22.

Research output: Contribution to journalReview article

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Gamage N, Barnett A, Hempel N, Duggleby RG, Windmill KF, Martin JL et al. Human sulfotransferases and their role in chemical metabolism. Toxicological Sciences. 2006 Mar 1;90(1):5-22. https://doi.org/10.1093/toxsci/kfj061