5 -phosphoadenosine 3 -phosphosulfate

Kim HJ, Cho JH, Klaassen CD. 1995. Depletion of hepatic 3 -phosphoadenosine 5 -phosphosulfate (PAPS) and sulfate in rats by xenobiotics that are sulfated. J Pharmacol Exp Ther 275 654-658. 

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-... 

Marsolais, F. et al., 3 -Phosphoadenosine 5 -phosphosulfate binding site of flavonol 3-sulfotrans-ferase studied by affinity chromatography and P-31 NMR. Biochemistry, 38, 4066, 1999. 

Phosphatidylinositol (Ptdlns) 563, 565, 566s in signalling 563 - 566 Phosphatidylinositol 3-kinase 565 Phosphatidylinositol 4,5-bisphosphate 563 Phosphatidylserine 383s, 564 decarboxylation of 753 Phosphatidylserine decarboxylase 409, 755 3 -Phosphoadenosine 5 -phosphosulfate (PAPS) 659 Phosphoadenylation... 

In Renilla the coelenterazine is stored as a coelenterazine sulfate, possibly having the structure shown. To convert this storage form to the active luciferin the sulfo group is transferred onto adenosine 3, 5 -bisphosphate to form 3 -phosphoadenosine 5 -phosphosulfate, the reverse of step d of Eq. 17-38. Tire luciferin of the ostracod crustacean Vargula hilgendorfii has a structure (Fig. 23-51) close to that from Renilla. 

Among the variety of sulfate esters formed by living cells are the sulfate esters of phenolic and steroid compounds excreted by animals, sulfate polysaccharides, and simple esters, such as choline sulfate. The key intermediate in the formation of all of these compounds lias been shown to be 3 -phosphoadenosine-5/-phosphosulfate (PAPS). This nucleotide also serves as an intermediate in sulfate reduction. 

Formation of 3 -phosphoadenosine-5 -phosphosulfate (PAPS), an active intermediate involved in sulfate reduction. The eight-electron reduction of S042 to HjS is poorly understood except for the initial steps in the activation of sulfate (shown in yellow). Reduction in yeast and plants involves the APS derivative shown. In E. coli a PAPS derivative is used. 

Sulfation is expensive in energy terms for the cell, since two molecules of ATP are necessary for the synthesis of one molecule of 3 -phosphoadenosine 5 -phosphosulfate (PAPS). Both enzymes involved in the synthesis of PAPS, ATP sulfurylase, and APS kinase, reside within a single bifunctional cytosolic protein of approximately 56 kDa, where substrate channeling of APS from ATP sulfurylase to APS kinase occurs. Several group VI anions other than sulfate can also serve as substrates, although the resultant anhydrides are unstable. Because this instability would lead to the overall consumption of ATP, these other anions can exert a toxic effect by depleting the cell of ATP. 

Phosphoadenosine -5 -phosphosulfate Sulfate group Bacteria, archaea and eukaryotes ... 

Different phenol sulfotransferases have been identified in the soluble fraction of especially the liver that use 3 -phosphoadenosine-5 -phosphosulfate as sulfate donor [16]. Examination of the substrate preferences of partially purified phenol sulfotransferases has indicated higher rates of sulfation of 3,3 -T2 than of T, and negligible sulfation of T4 and rT3 [17],... 

A second important conjugation reaction is the sulfate conjugation. This, again, occurs predominantly with hydroxy groups and occasionally with amino groups. The sulfate donor is 3 -phosphoadenosine-5 -phosphosulfate, which is formed from ATP and inorganic sulfate. The enzyme involved is sulfotransferase. 

Xu ZH (2001) Human 3 -phosphoadenosine 5 -phosphosulfate synthetase radiochemical enzymatic assay, biochemical properties and hepatic variation. Drug Metab Dispos 29 172-178... 

The sulfate molecule used in conjugation reactions is derived from 3-phosphoadenosine-5 -phosphosulfate (PAPS). Efficient synthesis of PAPS requires an adequate amount of inorganic sulfate with L-cysteine, D-cysteine, or L-methionine serving as precursors for the inorganic sulfate. PAPS is likely synthesized in every vertebrate cell, with high concentrations produced in the liver. 

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. 

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