PathwayStep2706 PathwayStep2707 PathwayStep2704 PathwayStep2705 PathwayStep2708 PathwayStep2709 PathwayStep2715 PathwayStep2716 PathwayStep2717 PathwayStep2718 PathwayStep2719 PathwayStep2710 PathwayStep2711 PathwayStep2712 PathwayStep2713 PathwayStep2714 PathwayStep2721 PathwayStep2720 Cytosolic sulfonation of small molecules Authored: Jassal, B, 2004-11-29 11:42:34 Edited: Jassal, B, 2008-05-19 12:57:01 GENE ONTOLOGYGO:0050427 Pubmed10503886 Pubmed11154739 Pubmed12372849 Pubmed15167709 Pubmed16322073 Pubmed9034160 Reactome Database ID Release 43156584 Reactome, http://www.reactome.org ReactomeREACT_6913 Two groups of sulfotransferease (SULT) enzymes catalyze the transfer of a sulfate group from 3-phosphoadenosine 5-phosphosulfate (PAPS) to a hydroxyl group on an acceptor molecule, yielding a sulfonated acceptor and 3-phosphoadenosine 5-phosphate (PAP). One is localized to the Golgi apparatus and mediates the sulfonation of proteoglycans. The second, annotated here, is cytosolic and mediates the sulfonation of a diverse array of small molecules, increasing their solubilities in water and modifying their physiological functions. There are probably thirteen or more human cytosolic SULT enzymes; eleven of these have been purified and characterized enzymatically, and are annotated here (Blanchard et al. 2004; Gamage et al. 2005). These enzymes appear to be active as dimers. Their substrate specificities are typically broad, and not related in an obvious way to their structures; indeed, apparently orthologous human and rodent SULT enzymes can have different substrate specificities (Glatt 2000), and none has been exhaustively characterized. The substrates listed in the table and annotated here are a sample of the known ones, chosen to indicate the range of activity of these enzymes and to capture some of their known physiologically important targets. Absence of a small molecule - enzyme pair from the table, however, may only mean that it has not yet been studied. Formation of PAPS beta-estradiol + PAPS => beta-estradiol 3-sulfate + PAP lithocholate + PAPS => lithocholate sulfate + PAP taurolithocholate + PAPS => taurolithocholate sulfate + PAP Adenosine 3',5'-bisphosphate (PAP) + H2O => AMP + orthophosphate 27-hydroxycholesterol + PAPS => 27-hydroxycholesterol 3-sulfate + PAP pregnenolone + PAPS => pregnenolone sulfate + PAP estrone + PAPS => estrone 3-sulfate + PAP dehydroepiandrosterone (DHEA) + PAPS => DHEA sulfate + PAP N-hydroxy-2-acetylaminofluorene + PAPS => 2-acetylaminofluorene-N-sulfate + PAP cholesterol + PAPS => cholesterol sulfate + PAP p-nitrophenol + PAPS => p-nitrophenol sulfate + PAP N-hydroxy-4-aminobiphenyl can form a sulfate conjugate Acetaminophen can form an O- sulfate conjugate 3,5,3'-triiodothyronine + PAPS => 3,5,3'-triiodothyronine 4-sulfate + PAP 3,3'-diiodothyronine + PAPS => 3,3'-diiodothyronine 4-sulfate + PAP Dopamine can form an O-sulfate conjugate Phenol can form a sulfate conjugate