Ethereal sulfate conjugation

The metabolism of thiophene (100) was first studied in 1886 by Heffter (1886MI10900), who administered it orally to dogs and noted the increased output of ethereal sulfates in urine. This is typical of aromatic hydrocarbons conversion to phenolic products which are excreted in urine as sulfate conjugates. When fed to rabbits, there was no increase in the ethereal sulfate output, but there was some indirect evidence of the presence in urine of dihydrodiols and thienylmercapturic acids (45MI10900). This was confirmed by Bray and coworkers (71MI10906,68BJ(109)11P>, who studied thiophene and benzothiophene metabolism in rabbits and rats. The only identifiable metabolites in urine were the thienylmercapturic acids (101) and (102), which are probably formed via conjugation of the intermediate... 

The glycosidic linkage of III bears a physiological resemblance to that of another conjugation product found in urine, the phenolic acid (or ethereal ) sulfate (V). Many phenols can be conjugated with either D-glucuronic acid or sulfuric acid ... 

The absence of p-coumaric and p-hydroxyphenylpropionic acids from normal urine of man and rabbit would indicate that the transformation of these acids into p-hydroxybenzoic acids (through P-oxidation) is more rapid in these species than in the rat. The same authors found also, in the urine of rats, coumaroylglycine and the ethereal sulfate of p-hydroxybenzoic acid, this conjugate being the only metabolite of p-hydroxybenzoic acid (B21). 

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). 

A small amount of the oxidation product was conjugated as an ethereal sulfate. 

Rats that had been injected with azobenzene produced urines contmning aniline, increased amounts of ethereal sulfates and glucuronosides and a compound which, when heated with strong hydrochloric acid, yielded benzidine (94). The precursor of benzidine was assumed to be hydrazobenzene which was suggested as-the primary metabolite. Williams (447) suggested that the ethereal sulfate and conjugated glucuronic acid probably result from products of further oxidation of aniline, such as p-aminophenol, and possibly phenolic derivatives of hydrazobenzene. 

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