Sulfotransferase SULT

Conjugations can also be brought about by sulfotransferases (SULTs) and glutathi-one-S-transferases (GSTs), both of which exist in a number of isoenzymic forms. Amines and alcohols are sulfate acceptors and SULTs are important in steroid hormone and catecholamine metabolism and like the UGTs require the sulfate to be activated prior to its incorporation into the target molecule (Figure 6.32). In this case, sulfate is activated at the expense of two molecules of ATP to form the final sulfate carrier PAPS O -phosphoadenosine-S -phosphosulfate). 

NAT, acetylation of nitrogen), sulfotransferases (SULT, formation of sulfate esters) and methyltransferases (MT, addition of methyl group). 

Sulfotransferases (SULTs) are important for the metabolism of a number of drugs, neurotransmitters, and hormones, especially the steroid hormones. The cosubstrate for these reactions is 3 -phosphoadenosine 5 -phosphosulfate (PAPS) (Fig. 4.1). Like the aforementioned enzymes, sulfate conjugation typically renders the compound inactive and more water soluble. However, this process can also result in the activation of certain compounds, such as the antihypertensive minoxidil and several of the steroid hormones. Seven SULT isoforms identified in humans, including SULTs lAl to 1A3, possess activity toward phenolic substrates such as dopamine, estradiol, and acetaminophen. SULTIBI possesses activity toward such endogenous substrates as dopamine and triiodothyronine. SULTIEI has substantial activity toward steroid hormones, especially estradiol and dehydroepiandrosterone, and toward the anti-... 

Zra -resveratrol-4 -0-sulfate (S2), and traras-resveratrol-3-O-sulfate (S3), respectively. Incubation in the presence of human recombinant sulfotransferases (SULTs) demonstrated that SI is almost exclusively catalyzed by SULT1A1 and only to a minor extent by SULT 1A2, 1A3, and 1E1, whereas S2 is selectively formed by SULT1E1. S3 is catalyzed by SULT1A1, SULT1E1, SULT1A2, and 1A3 (depending on the resveratrol concentration) [Miksits et al., 2005]. The metabolic pathway of resveratrol in human liver cytosol in vitro is shown in Figure 14.4. 

Glatt, H. and Meinl, W., Pharmacogenetics of soluble sulfotransferases (SULTs), Naunyn Schmiedebergs Arch. Pharmacol., 369, 55, 2004. 

Sulfotransferases (SULTs) are cytosolic phase II detoxification enzymes involved in sulfonation of various xenobiotics and endobiotics. There are also membrane-bound SULTs that are not involved in phase II metabolism but are involved in the sulfonation of proteins and polysaccharides. Substrates of cytosolic SULTs include alcohols (ethanol, 2-butanol, cholesterol, bile acids), phenols (phenol, naphthol, acetaminophen), aromatic amines and hydroxyamines (2-naphthylamine, A-hydroxy 2-naphthylamine). SULTs transfer sulfonate (S03) to a hydroxy or amino group of a substrates from the cofactor 3 -phosphoadenosine-5 -phosphosulfate (PAPS), generating highly water-soluble metabolites for elimination through the kidney and liver. 

The sulfotransferase (SULT) enzymes belong to a superfamily of enzymes that catalyze sulfation reactions. The sulfation reaction involves high-energy inputs from the cell because two molecules of ATP are necessary for the synthesis of one molecule of 3 -phosphoadenosine 5 -phosphosulfate (PAPS). The amino acids cysteine and methionine are the major sources of sulfate required for PAPS synthesis, Cellular concentrations of PAPS arc considerably less than those of UDPGA and glutathione, limiting the capacity for sulfation. 

Hepatic cytosol contains three important soluble DMEs that aren t found in microsomes, N-acetyl transferase NAC), sulfotransferase (SULT, sometimes abbreviated ST), and glutathione S-transferase (GST). When the appropriate co-factors, like Acetyl CoA for NAC, are added stability to these three conjugating enzymes can be studied. 

Blanchard et al., 2004 Blanchard RL, Freimuth RR. et al. A proposed nomenclature system for the cytosolic sulfotransferase (SULT) superfamily. Pharmacogenetics 2004 14(3) 199-211. 

Nagar S, Walther S. et al. Sulfotransferase (SULT) lAl pol5morphic variants 1, 2, and 3 are associated with altered enzymatic activity, cellular phenotype, and protein degradation. Mol Pharmacol 2006 69(6) 2084-2092. 

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