Conjugated steroids, metabolism

M2. Mason, M., Effects of conjugated steroids on enzymes. In Metabolic Conjugation and Metabolic Hydrolysis (W. H. Fishman, ed.), Vol. 1, pp. 121-156. Academic Press, New York, 1970. 

Metabolic studies carried out with isotopically labeled dehydroepi-androsterone sulfate [312] showed that this conjugated steroid may follow an indirect metabolic pathway initiated by the hydrolysis of the sulfate group. In the course of the metabolism the conjugated steroid thus becomes a free steroid first and the free steroid may undergo further metabolism. On the other hand, dehydroepiandrosterone sulfate may follow a direct metabolic pathway without a break of the ester group. 

In the first place the discovery of the secretion of DHA-sulfate by the adrenal cortex in apparently major quantities suggested a hitherto completely unsuspected role of steroid sulfates in steroid biosynthesis and metabolism. Second, a number of steroid metabolites conjugated with two molecules of glucuronic or sulfuric acid were discovered, particularly in pregnancy urine, amniotic fluid, and in perfused placentofetal preparations. Finally, isotopic studies revealed several cases in which administered doubly labeled steroid conjugates were metabolized in the steroid part of the molecule without hydrolysis of the conjugate (e.g., D4, R5 cf. B5). 

U2. Ulstrom, R. A., Colle, E., Burley, J., and Gunville, R., Adrenocortical steroid metabolism in newborn infants. I. Urinary excretion of free and conjugated 17-hydroxycorticosteroids in normal full-term infants. J. Clin. Endocrinol. Metab. 20, 1066-1079 (1960). 

Animal Steroid Metabolism.—The reduction of the A -double bond of cholesterol has already been discussed for plants. A similar process occurs in animals. Oxidation at C-3 is followed by an isomerisation to give the conjugated 4-en-3-one system. In rat livers a substantial isotope effect is observed when either the... 

Hence the time factor in indirect metabolism is very important. When a steroid conjugate is metabolized indirectly, the kinetics of its hydrolysis and/or the arrival of the conjugate at the sites of hydrolysis may be limiting factors, resulting in lower conversion rates, and one can speak of delayed or protected metabolism (Baulieu et al., 1965). 

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

Protein isolation, by conjugating, 13 748 Protein kinases, 20 832 Protein metabolism, anabolic steroids and, 13 5-6... 

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). 

Dumasia MC, Houghton E, Bradley CV, Williams DH. 1983. Studies related to the metabolism of anabolic steroids in the horse the metabolism of 1-dehydrosterone and the use of fast atom bombardment mass spectrometry in the identification of steroid conjugates. Biomed Mass Spectrom 10 434-440. 

The steroid hormones are mainly inactivated in the liver, where they are either reduced or further hydroxylated and then conjugated with glucuronic acid or sulfate for excretion (see p. 316). The reduction reactions attack 0X0 groups and the double bond in ring A. A combination of several inactivation reactions gives rise to many different steroid metabolites that have lost most of their hormonal activity. Finally, they are excreted with the urine and also partly via the bile. Evidence of steroids and steroid metabolites in the urine is used to investigate the hormone metabolism. 

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