Abstract
The cytosolic sulfotransferases (SULTs) are phase II conjugating enzymes that catalyze the transfer of a sulfonate group from the universal sulfate donor 3′-phosphoadenosine-5′-phosphosulfate to a nucleophilic group of their substrates to generate hydrophilic products. Sulfation has a major effect on the chemical and functional homeostasis of substrate chemicals. SULTs are widely expressed in metabolically active or hormonally responsive tissues, including the liver and many extrahepatic tissues. The expression of SULTs exhibits isoform-, tissue-, sex-, and development-specific regulations. SULTs display a broad range of substrates including xenobiotics and endobiotics. The expression of SULTs has been shown to be transcriptionally regulated by members of the nuclear receptor superfamily, such as the peroxisome proliferator–activated receptors, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, liver X receptors, farnesoid X receptor, retinoid-related orphan receptors, estrogen-related receptors, and hepatocyte nuclear factor 4α. These nuclear receptors can be activated by numerous xenobiotics and endobiotics, such as fatty acids, bile acids, and oxysterols, many of which are substrates of SULTs. Due to their metabolism of xenobiotics and endobiotics, SULTs and their regulations are implicated in the pathogenesis of many diseases. This review is aimed to summarize the central role of major SULTs, including the SULT1 and SULT2 subfamilies, in the pathophysiology of liver and liver-related diseases.
SIGNIFICANCE STATEMENT Sulfotransferases (SULTs) are indispensable in the homeostasis of xenobiotics and endobiotics. Knowing SULTs and their regulations are implicated in human diseases, it is hoped that genetic or pharmacological manipulations of the expression and/or activity of SULTs can be used to affect the clinical outcome of diseases.
Footnotes
- Received April 11, 2020.
- Accepted June 8, 2020.
Our original work described in this review article was supported in part by National Institutes of Health [Grants DK117370 and ES030429] (to W.X.). W.X. was supported in part by the Joseph Koslow Endowed Professorship from the University of Pittsburgh School of Pharmacy.
The data contained in this manuscript were presented in part from the doctoral dissertation of Y.X. (http://d-scholarship.pitt.edu/38357/).
- Copyright © 2020 by The American Society for Pharmacology and Experimental Therapeutics
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