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Citation
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HERO ID
5356761
Reference Type
Journal Article
Subtype
Review
Title
Sulfation and sulfotransferases 5: the importance of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in the regulation of sulfation
Author(s)
Klaassen, CD; Boles, JW
Year
1997
Is Peer Reviewed?
Yes
Journal
FASEB Journal
ISSN:
0892-6638
EISSN:
1530-6860
Volume
11
Issue
6
Page Numbers
404-418
Language
English
PMID
9194521
DOI
10.1096/fasebj.11.6.9194521
Web of Science Id
WOS:A1997XE40400003
Abstract
Sulfation is the transfer of a sulfate group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to a substrate that is catalyzed by a family of sulfotransferase enzymes. Many different endogenous and xenobiotic molecules are substrates for the sulfotransferases; sulfation affects many different physiological processes, including: 1) deactivation and bioactivation of xenobiotics, 2) inactivation of hormones and catecholamines, 3) structure and function of macromolecules, and 4) elimination of end products of catabolism. PAPS is the obligate cosubstrate that is synthesized in tissues to make available an "activated form" of sulfate for the sulfation reaction. PAPS participation in the reaction is dependent on its availability, which in turn is dependent on its synthesis, degradation, and ultimately its utilization in the sulfation reaction itself. PAPS synthesis is dependent on the availability of sulfate and on the activity of the two enzymes of its synthesis, ATP-sulfurylase and APS-kinase. Although the kinetic properties of these two enzymes are well described, their in vivo regulation is not fully understood. Sulfation is a high-affinity, low-capacity enzymatic process in which the entire liver content of PAPS can be consumed in less than 2 min. ATP-sulfurylase and APS-kinase can rapidly synthesize additional PAPS. The low capacity of sulfation in rats is due to the limited availability of sulfate, whereas in mice the sulfotransferases appear to limit sulfation capacity. Sulfation rates are not readily enhanced, but they can be decreased. 2,6-Dichloro-4-nitrophenol inhibits phenolsulfotransferases, but not hydroxysteroid-sulfotransferases. However, the sulfation of phenols and hydroxysteroids can be decreased by factors that decrease sulfate availability such as a low-sulfate diet, other xenobiotics that are sulfated, and molybdate, which inhibits sulfate intestinal absorption, renal reabsorption, and sulfate incorporation into PAPS.
Keywords
acetaminophen; sulfate; ATP-sulfurylase; APS-kinase; glutathione
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