Sulfation sulfotransferases, cytosol

Sulfate conjugation PAP-sulfate Sulfotransferase (cytosol) Phenols alcohols aromatic amines... 

Sulfation Phosphoadenosyl phosphosulfate Sulfotransferase (cytosol) Phenols, alcohols, aromatic amines Estrone, aniline, phenol, 3-hydroxy-coumarin, acetaminophen, methyldopa... 

Sulfotransferases are cytosolic enzymes that add sulfate to phenolic and hydroxyl functions as well as certain amines. The relative rates of sulfation of several sulfo-... 

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. 

Falany JL et al (2006) Sulfation of raloxifene and 4-hydroxytamoxifen by human cytosolic sulfotransferases. Drug Metab Dispos 34 361-368... 

Sulfotransferases located in the cytosol are involved in the sulfation (Coughtrie and Fisher 2003). An overview on isoforms and their characteristics is given in Table 4. 

The sulfotransferase enzymes comprise a superfamily of enzymes. These enzymes can either be membrane-bound or cytosolic, though the enzymes involved in xeno-biotic conjugation are primarily cytosolic. Several members of the sulfotransferase superfamily that are significant contributors to the sulfation of xenobiotics have been identified in humans. Provided below is a brief description of the known human SULTs. 

Pacifid, G.M. (2005) Sulfation of drugs, in Human Cytosolic Sulfotransferases (eds... 

Sulfation is another common form of conjugation predominately found with phenolic compounds however, sulfate esters can also be formed with alcohols, aryl-amines, and N-hydroxy compounds. Sulfation involves the transfer of S03 from 3 -phosphoadenosine-5 -phosphosulfate (PAPS) to one of the above-mentioned functional groups by an enzyme-catalyzed reaction involving the cytosolic enzymes (sulfotransferases), as illustrated in Fig. 24 [11]. It is common to find phenolic compounds that are metabolized by both sulfation and glucuronidation, as they are often competing pathways. However, sulfation has a significant limitation... 

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]. 

Part II Sulfate Conjugate-Dependent Toxicity Biochemistry of Cytosolic Sulfotransferases Involved in Bioactivation... 

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. 

Anderson RJ, Kudlacek PE, Clemens DL. Sulfation of minoxidil by multiple human cytosolic sulfotransferases. Chem Biol Interact 1998 109 53-67. 

Pharmacometrics of stilbenes and its relationship with clinical studies were recently reviewed [9]. The aim of the research [31] was to study the sulfation of resveratrol in the human liver and duodenum. A simple and reproducible radiometric assay for resveratrol sulfation was developed. It employed 3 -phosphoadenosine-5 -phospho-sulfate-[35S] as the sulfate donor, and the rate of resveratrol sulfation (pmol/min/mg cytosolic protein) were found to be 90 (liver) and 74 (duodenum). Resveratrol sulfotransferase followed Michaelis-Menten kinetics, and (fiM) was 0.63 (liver) and 0.50 (duodenum) and (pmol/min/mg cytosolic protein) were 125 (liver) and... 

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