Sulfate conjugation

Sulfate conjugates have been detected in vivo in numerous insect species following exposure to phenolic compounds. A sulfotransferase prepared from gut tissues of southern armyworm larvae has been shown to be active toward p-nitrophenol and steroids, including cholesterol, eedysone, and p-sitosterol (Yang and Wilkinson, 1972). 

Sulfation and sulfate conjugate hydrolysis, catalyzed by various members of the sul-fotransferases (SULT) and sulfatase enzyme superfamilies, play important roles in the 

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. 

In humans, there are five well-characterized SULT genes, each possessing widely different amino acid sequences and with widely different substrate specificities. Based 

Hydroxysteroid sulfotansferase also appears to exist in several forms. This reaction is now known to be important, not only as a detoxication mechanism but also in the synthesis and possibly the transport of steroids. Hydroxysteroid sulfotransferase will react with hydroxysterols and primary and secondary alcohols but not with hydroxyl groups in the aromatic rings of steroids. 

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Only the small amounts of T and T that are free in the circulation can be metabolized. The main route is deiodination of T to T and i-T, and from these to other inactive thyronines (21). Most of the Hberated iodide is reabsorbed in the kidney. Another route is the formation of glucuronide and sulfate conjugates at the 4 -OH in the Hver. These are then secreted in the bile and excreted in the feces as free phenols after hydrolysis in the lower gut. 

About 97% of po dose is absorbed from the GI tract. The dmg undergoes extensive first-pass hepatic metaboHsm and only 12% of the po dose is bioavailable. More than 95% is protein bound and peak plasma concentrations are achieved in 2—3 h. Therapeutic plasma concentrations are 0.064—1.044 lg/mL. The dmg is metabolized in the Hver to 5-hyroxypropafenone, which has some antiarrhythmic activity, and to inactive hydroxymethoxy propafenone, glucuronides, and sulfate conjugates. Less than 1% of the po dose is excreted by the kidney unchanged. The elimination half-life is 2—12 h (32). 

MRP1 (ABCC1) Glucuronides and sulfate conjugates of steroid hormones and bile salts, colchicine, doxorubicin, daunorubicin, epirubicin, folate, irinotecan, methotrexate, pacitaxel, vinblastine, vincristine, and others... 

Alternative pathways of activation of nitrosamines, including 3-hydroxylation followed by sulfate conjugation and the formation of alkoxydiazen-ium ions are discussed. The formation of alkyldiazo-nium ions from trialkyltriazenes is presented to show that the formation of the putative ultimate carcinogens from nitrosamines can be studied in a system not requiring metabolic activation,... 

Asai, A. and Miyazawa, T., Occurrence of administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma, Life Sci., 67, 2785, 2000. 

Cerniglia CE, JP Freeman, RK Mitchum (1982b) Glucuronide and sulfate conjugation in the fungal metabolism of aromatic hydrocarbons. Appl Environ Microbiol 43 1070-1075. 

Pesoia, G. R., Walle, T., Stereoselective sulfate conjugation of isoproterenol in humans comparison of hepatic, intestinal and platelet activity, Chirality 1993, 5, 602-609. 

Stehly, G.R. and W.L. Hayton. 1988. Detection of pentachlorophenol and its glucuronide and sulfate conjugates in fish bile and exposure water. Jour. Environ. Sci. Health B23 355-366. 

The concept of microbial models of mammalian metabolism was elaborated by Smith and Rosazza for just such a purpose (27-32). In principle, this concept recognizes the fact that microorganisms catalyze the same types of metabolic reactions as do mammals (32), and they accomplish these by using essentially the same type of enzymes (29). Useful biotransformation reactions common to microbial and mammalian systems include all of the known Phase I and Phase II metabolic reactions implied, including aromatic hydroxylation (accompanied by the NIH shift), N- and O-dealkylations, and glucuronide and sulfate conjugations of phenol to name but a few (27-34). All of these reactions have value in studies with the alkaloids. 

Many drugs and metabolites are metabolized by conjugation with sulfate or glucuronic acid as described in Chapter 7. Sulfate conjugates can be hydrolyzed back to the alcohol or phenol. Glucuronide conjugates can involve a wider variety of functional groups and... 

Jedlitschky, G., Leier, I., Buchholz, U., Barnouin, K., Kurz, G. and Keppler, D. (1996) Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Research, 56, 988-994. 

The present paper deals with a relation between toxicity and accumulation of chlorophenols in goldfish, Carassius auratus, PCP metabolites and their amounts excreted by the three major routes (branchial, renal and biliary) in the fish, and also with effects of pre-exposure to PCP on PCP-tolerance and on sulfate conjugation with phenol by the liver soluble fraction of the fish. 

No other conjugates including the sulfate-conjugate were detected in the bile(6). 

A PCP-conjugate excreted by short-necked clam, Tapes philip-pinarum. into surrounding water has been also identified as the sulfate-conjugate(9). 

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