Phosphoadenosine phosphosulfate PAPS active sulfate

The biosynthesis of sulfate esters with the help of phosphoadenosine phosphosulfate (PAPS), the active sulfate , (see p. 110) and amide formation with glycine and glutamine also play a role in conjugation. For example, benzoic acid is conjugated with glycine to form the more soluble and less toxic hippuric acid (N-benzoylglycine see p. 324). 

Another conjugative reaction, particularly of phenolic hydroxyl groups, is ethereal sulfate formation. The cytosol portion of liver cells contains enzymes that activate sulfate to a form transferrable to acceptors. Thus 3 -phosphoadenosine-5 -phosphosulfate (PAPS) will sulfate phenols to ethereal sulfates (actually half-esters of sulfuric acid), thus increasing their polarity and excretability greatly (Fig. 3-3). 

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-... 

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. 

Two major pathways are known for the reduction of sulfate. One is the assimilatory pathway, which reduces sulfate to the extent necessary for satisfying the nutritional requirements of the organism. In this pathway, which has been extensively studied in yeast by Robbins and Lip-mann (S68) and Bandurski and his colleagues 369, 370), sulfate is first activated in the presence of ATP by the enzyme ATP-sulfurylase to form adenosine 5 -phosphosulfate (APS). Then in a second reaction, APS is phosphorylated in the 3 position by ATP to form 3 -phosphoadenosine 5 -phosphosulfate (PAPS)... 

Sulfotransferases transfer sulfo groups to O and N atoms of suitable acceptors (reaction type ID, Table 10-1). Usually, transfer is from the active sulfate," 3 -phosphoadenosine 5 -phosphosulfate (PAPS), 21 whose formation is depicted in Eq. 17-38. Sulfatases catalyze hydrolysis of sulfate esters. The importance of such enzymes is demonstrated by the genetic mucopolysaccharidoses. In four of these disease-specific sulfatases that act on iduronate sulfate, heparan N-sulfate, galactose-6-sulfate, or N-acetylglu-cosamine-4-sulfate are absent. Some of these, such as heparan N-sulfatase deficiency, lead to severe mental retardation, some cause serious skeletal abnormalities, while others are mild in their effects. ... 

Phosphoadenosine 5 -phosphosulfate (PAPS) is the well-known sulfate donor that occupies a central position in sulfate biochemistry (Balasubrama-nian and Bachhawat, 1970 DeMeoi, 1975 Farooqui, 1980b). It is hydrolyzed into PAP and sulfate by PAPS sulfohydrolase (Balasubramanian and Bachhawat, 1962). Nothing has been reported on the purification of this enzyme, but the crude enzyme preparation shows optimal activity at pH 6.0. It is activated by Co " " and Mn " " and inhibited by ADP, fluoride, and sulfhydryl compounds (Balasubramanian and Bachhawat, 1962). The desulfation of PAPS is a specific reaction. Arylsulfohydrolase A from chicken brain and rabbit kidney cortex does not hydrolyze PAPS to PAP (Farooqui and Bachhawat, 1972 Farooqui and Helwig, unpublished). Because PAPS sulfohydrolase has never been purified from any source, nothing is known about its physicochemical properties. 

A cytosolic sulfotransferase has been identified in rat liver and kidney which utilizes 3 -phosphoadenosine-5 -phosphosulfate (PAPS) and shows a greater rate of sulfation for glycolithocholate than lithocholate. In an assay with the enzyme preparation, PAPS, and conjugated bile acids, 3 unidentified products were formed from taurocholate suggesting multiple sulfation of more polar conjugated bile acids [64]. The enzyme from liver, proximal intestine or adrenals of hamster produced only glycochenodeoxycholate 7-sulfate. Comparable results with the enzyme from kidney will be discussed in Section VI.3. Hepatic enzyme from the female hamster shows 4-fold greater activity than that of the male [65]. 

Ceramide reacts with phosphatidylcholine to form sphingomyelin, a component of the myelin sheath (Fig. 33.33). Ceramide also reacts with UDP-sugars to form cerebrosides (which contain a single monosaccharide, usually galactose or glucose). Galactocerebroside may react with 3 -phosphoadenosine 5 -phosphosulfate (PAPS, an active sulfate donor Figure 33.34) to form sulfatides, the major sulfolipids of the brain. 

The transfer of a sulfonate group from the donor compound 3 -phosphoadenosine 5 -phosphosulfate (PAPS) to an acceptor compound (such as TH, steroids,. .. but also xenobiotics) is catalyzed by a large family of enzymes called sulfotransferases, located in the cytoplasmic fraction of, e.g., liver cells. Unlike glucuronidation, sulfation does not facilitate the excretion ofTH, but interferes with the deio-dination process. Sulfated THs strongly facilitate the IRD activity of D1 while they inhibit the D2, D3 activity, and theORDofDl Moreno et al., 1994 VisserT. J., 1990). 

An alternative mechanism for the esterification of V-OH-AAF is the conversion of 4 to 6, as shown in Fig. 1. 31). The formation of A-acetoxy-AAF can occur by a one-electron oxidation process (Fig. 2). This reaction is catalyzed by various peroxidases (29, 31). In addition to the formation of A-acetoxy-AAF, the potential for the formation of the electrophilic sulfate esters of A-OH-AAF was also studied in vitro. It was demonstrated that 3 -phosphoadenosine-5 -phosphosulfate (PAPS) in the presence of rat liver cytosol catalyzed the formation of the sulfate ester of A-OH-AAF. With the exception of the rabbit, the presence of sulfotransferase activity correlated with the susceptibility of the liver of the various species shown in Table V to the carcinogenic activity of N-OH-AAF. 

Conjugation of phenols, aliphatic and steroid alcohols with sulfate occurs in mammals, birds, reptiles, amphibia, but not in fish. In addition, active sulfate in the presence of transferase will conjugate aromatic amines and form sulfamates [70] in mammals, birds, and spiders. The synthesis of sulfate derivatives occurs in the soluble fraction of liver homogenates through the formation of adenosine-5 -phosphosulfate (APS) and 3 -phosphoadenosine-5 -phosphosulfate (PAPS) [21]. The reactions may be written as follows ... 

Trebst and Schmidt have reported that sulfate reduction by leaves is localized in the chloroplast and that complete photoreduction of sulfate to sulfide and S-containing amino acids can be accomplished in vitro in isolated chloroplasts. Assimilatory sulfate reduction has been assumed to occur by sulfate activation with ATP to 3 -phosphoadenosine-5 -phosphosulfate (PAPS), reduction of PAPS to sulfite presumably by NADPH and further... 

Sulfotransferases catalyze the transfer of a sulfate (i.e., sulfonate, SO3) group from an activated donor onto the hydroxyl or less commonly the amino group of the acceptor molecule. The activated donor is invariably 3 phosphoadenosine 5 phosphosulfate (PAPS) [4]. PAPS is synthesized from ATP and S04 by the sequential action of ATP sulfurylase, which generates adenosine 5 phosphosulfate (APS), and APS kinase, which transfers a phosphate from ATP to APS. Chlorate, a drug which has been extremely useful for implicating the importance of sulfation... 

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). 

Inorganic sulfur in the environment (sulfate, sulfur, or sulfite) must undergo fixation to be ulitized by organisms. The process for sulfate is largely confined to plants and bacteria. Activation of sulfur for reduction is in the form of the intermediate called PAPS (3 -phosphoadenosine-5 -phosphosulfate) (see here). PAPS is formed in a two-step reaction (see here). 

When cysteine is degraded, the nitrogen is converted to urea, the carbons to pyruvate, and the sulfur to sulfate, which has two potential fates (see Fig. 39.7 see also Chapter 43). Sulfate generation, in an aqueous media, is essentially generating sulfuric acid, and both the acid and sulfate need to be disposed of in the urine. Sulfate is also used in most cells to generate an activated form of sulfate known as PAPS (3 -phosphoadenosine 5 -phosphosulfate), which is used as a sulfate donor in modifying carbohydrates or amino acids in various structures (glycosaminoglycans) and proteins in the body. 

The sulfatide isolated was soluble in chloroform-methanol (2—1) and failed to partition into an aqueous phase. Further identification of the sulfolipid was not made. Goldberg (1961) has postulated several pathways which may be involved in cerebroside sulfate synthesis. The initial steps are the activations of sulfate to 3 -phosphoadenosine-5 -phosphosulfate, i.e., PAPS, as described by Bandurski et al. (1956, 1958), Wilson and Bandurski (1956), and Robbins and Lipmann (1956, 1958a, b). 

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