Sulfo conjugates

Felgines, C., Strawberry anthocyanins are recovered in urine as glucuro- and sulfo-conjugates in humans, J. Nutr., 133, 1296, 2003. 

Glutathione and sulfatation conjugations are important pathways for generally detoxifying endogenous substrates and xenobiotics (Commanndeur et al. 1995). However, some produced metabolites (ie mercapturic acids, O-sulfo conjugates) are toxic by different mechanisms, often by reaction with DNA and other cellular nucleophiles. 

The discovery of dehydroepiandrosterone sulfate secretion gave a new incentive to the whole study of conjugation, and it soon became evident that dehydroepiandrosterone sulfate could not only be biosynthesized from sulfo conjugated percursors along a direct biosynthetic pathway, but could also undergo further metabolism, with or without hydrolysis of the sulfate moiety (i.e., indirect or direct metabolism) and act as a privileged precursor of active steroids. 

However new questions were asked Are other steroid conjugates secreted How and where are these secreted products biosynthesized and metabolized Are the sulfo conjugates biologically active, and what is their role in hormonal regulation Only a few of these questions can be answered yet. 

It was thus established that the enzymes involved in the biosynthesis of adrenal androgens could have sulfo conjugated compounds as substrates, but one had yet to discover whether cholesterol sulfate was the initial precursor and what was the quantitative importance of this sulfate pathway. 

In the kidney, one finds glucuronyltransferases (Dutton, 1966) but little or no steroid sulfotransferase (Bostrom and Wengle, 1967), whereas the intestine contains both enzyme systems, sulfotransferases in the intestinal wall (Baulieu et al., 1965) and glucuronyltransferases in the mucosa (Dutton, 1966). As intestinal metabolism of steroids is diflFerent in germ-free and conventional rats (GustafiFson and S jo vail, 1968), in diis animal, microorganisms in the intestine can enhance sulfo conjugation, which in turn, promotes fecal excretion a similar type of mechanism can exist in humans, yet complicated by the presence of bacterial sulfotransferases and sulfatases. 

Secretion of both testosterone sulfate and glucuronide by the testis (Saez et al., 1967 Ekstrom et al., 1968) suggests that both conjugating enzymes are present in this tissue, and some sulfurylation of dehydroe-piandrosterone has been observed in the brain (Knapstein et al., 1968). Skin has also been shown capable of sulfo conjugating dehydroepian-drosterone (Gallegos and Berliner, 1967). 

Fig. 8. Role of sulfo conjugated precursors in the biosynthesis of placental estrogens.

Data obtained in vivo (Baulieu et al, 1965) have shown (Fig. 9) that after an injection of radioactive dehydroepiandrosterone and dehydroe-piandrosterone sulfate, the free compound is transformed more rapidly and more eflBciently into androsterone and etiocholanolone than the sulfo conjugate, the latter being apparently protected from rapid liver catabolism. 

After the first demonstration of a direct metabolism of a steroid conjugate [androstenediol sulfate =i dehydroepiandrosterone sulfate (Baulieu et ah, 1963)], showing that a 17j8-hydroxysteroid oxidoreductase can have a sulfo conjugate as a substrate, other enzymic transformations of dehydroepiandrosterone sulfate were reported (Fig. 4). Dehydroepiandrosterone sulfate can undergo 16o -hydroxylation to 16a-hydroxy-dehydroepiandrosterone sulfate which can be further hydroxylated into androstenetriol sulfate its direct 17-hydroxylated metabolite, androstene-... 

After an injection of radioactive dehydroepiandrosterone sulfate, a small proportion is recovered as such in urine. However, if the double-labeled compound H-dehydroepiandrosterone sulfate- S is injected and its disappearance from the blood is observed, one finds different half-lives for H-dehydroepiandrosterone sulfate and for dehydroepiandrosterone sulfate- S (Fig. 10). This shows that there is a constant hydrolysis of the sulfo conjugate followed by a resulfation with sulfate from a large unlabeled pool (Fig. 3). In other words, the steroid moiety of dehydroepiandrosterone sulfate has a half-life of 9 hours, whereas the sulfate moiety has a shorter half-life of 6 hours, since the sulfate moiety is... 

Sulfo conjugated steroids are only partially excreted in the urine, and are largely metabolized, with or without hydrolysis of the ester bond. 

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