Human sulfotransferases and their role in chemical metabolism

Gamage, N., Barnett, A., Hempel, N., Duggleby, R. G., Windmill, K. F., Martin, J. L. and McManus, M. E. (2006) Human sulfotransferases and their role in chemical metabolism. Toxicological Sciences, 90 1: 5-22. doi:10.1093/toxsci/kfj061


Author Gamage, N.
Barnett, A.
Hempel, N.
Duggleby, R. G.
Windmill, K. F.
Martin, J. L.
McManus, M. E.
Title Human sulfotransferases and their role in chemical metabolism
Journal name Toxicological Sciences   Check publisher's open access policy
ISSN 1096-6080
Publication date 2006
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1093/toxsci/kfj061
Open Access Status Not Open Access
Volume 90
Issue 1
Start page 5
End page 22
Total pages 18
Editor Lois D Lehman-McKeeman
Virginia F Hawkins
Place of publication Oxford
Publisher Oxford Univ Press
Collection year 2006
Language eng
Subject C1
270108 Enzymes
320500 Pharmacology and Pharmaceutical Sciences
730108 Cancer and related disorders
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.
Keyword Human Sulfotransferases
Sult1a1 Regulation
Sult Crystal Structures
Bioactivation
Toxicology
Liver Dehydroepiandrosterone Sulfotransferase
Human Estrogen Sulfotransferase
Molecular-cloning
Crystal-structure
Phenol Sulfotransferase
Hydroxysteroid Sulfotransferase
Functional-characterization
Aryl Sulfotransferase
Cdna Cloning
Cytosolic Sulfotransferases
Q-Index Code C1

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Faculty of Science Publications
Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
 
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Created: Wed, 15 Aug 2007, 08:23:11 EST