3 -Phosphoadenosine

Lee KA, Fuda H, Lee YC, Negishi M, Strott CA, Pedersen LC. Crystal structure of human cholesterol sulfotransferase (SULT2Blb) in the presence of pregnenolone and 3 -phosphoadenosine 5 -phosphate. Rationale for specificity differences between prototypical SULT2A1 and the SULT2BG1 isoforms. I Biol Chem 2003 278 44593-9. 

JAIN, J.C., GROOTWASSINK, J.W.D., KOLENOVSKY, A.D., UNDERHILL, E.W., Purification and properties of 3-phosphoadenosine-5-phosphosulphate desulphoglucosinolate sulphotransferase from Brassica juncea cell cultures, Phytochemistry, 1990, 29, 1425-1428. 

The sulfotransferases catalyze formation of sulfate esters of compounds having hydroxy or amino groups. The donor in this transfer of a sulfuryl group is 3 -phosphoadenylsulfate, also named previously as 3 -phosphoadenosine-5 -phos-phosulfate (PAPS). An example of this reaction is seen in Eq. (11) for phenol as the sulfuryl (S03) acceptor, with the products of the reaction being phenyl sulfate and adenosine 3, 5 -bisphosphate (PAP). 

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). 

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. 

Example 17 Bertozzi and associates in their studies on sulfotransferases have performed synthesis of a bisubstrate analogue designed to inhibit estrogen sulfotransferase [45]. Synthesis of this diphosphate depends on the coupling of two phosphates prepared by phosphoroamidite methodology. The synthesis utilizes differently protected 3 -phosphoadenosine-5 -phos-phate allowing selective functionalization of the 5 -phosphate with the sulfate acceptor mimic. 

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). 

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. 

A variety of enzyme cofactors serving a wide range of chemical functions include adenosine as part of their structure (Fig. 8-41). They are unrelated structurally except for the presence of adenosine. In none of these cofactors does the adenosine portion participate directly in the primary function, but removal of adenosine generally results in a drastic reduction of cofactor activities. For example, removal of the adenine nucleotide (3 -phosphoadenosine diphosphate) from acetoacetyl-... 

The properties of 3 -phosphoadenosine-5 -phosphosulfaie (PAPS) the established sulfate donor in the formation of chrondrointin sulfate, cerebro-sulfatides and phenolic sulfates208 210 has been investigated through an appropriate model system211. The pH-rate profile for phenyl phosphosulfate given below (76), indicates that both the dianion and monoanion are definitely... 

Sulfotransferases917 920a 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 -phosphosuIfate (PAPS),921 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.922... 

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. 

---