Biotransformation is mediated by phase 1 biotransformation (cytochrome P450 and isoenzymes) and phase 2 biotransformation (sulfotransferase and … As sulfated estrogens are unable to bind to the estrogen receptors, sulfonation of estrogens results in their inactivation. Therefore, conjugation with sulfate protects cells and tissues from an excess of active estrogens, and this may contribute to the prevention of hormone-dependent cancer cells. It further Inhibitors,research,lifescience,medical indicates that the balance between sulfate conjugation by the Phase 2 metabolizing enzyme estrogen sulfotransferases (SULT1E1) and the removal of the sulfate by the steroid sulfotransferase (STS) is important to store the hormone in an inactive form

in the cells [16, 17]. Conjugation of lipophilic estrogens with sulfate is a main pathway for estrogen inactivation in estrogen target tissues. Sulfate conjugation of E2 is catalyzed by the Phase 2 drug metabolizing enzymes of the family of cytosolic sulfotransferases (SULTs) [18]. The isoform SULT1E1 Inhibitors,research,lifescience,medical is known as estrogen sulfotransferase, as it catalyzes the sulfonation of E1 and E2 with high efficiency at physiological concentrations. Inhibitors,research,lifescience,medical The

sulfate conjugation of androgenic precursors, for example, dehydroepiandrosterone (DHEA), is mainly achieved by another SULT isoenzyme, namely, the SULT2A1 enzyme [18]. Both, 5alpha-androstenediol-sulfat (Diol-S) and dehydroepiandrosterone (DHEA) are mainly derived from the circulation. Diol-S is converted to 5alpha-androstenediol (5-Diol) by STS. It is converted into PF-06463922 testosterone by 3beta-HSD. Dehydroepiandrosterone-sulfate (DHEA-S) is desulfonated to dehydroepiandrosterone (DHEA) and converted by 3beta-HSD to 4alpha-androstenedione (4-Dione), a precursor

for testosterone formed by 17beta-HSD. Inhibitors,research,lifescience,medical Testosterone is converted to E2 by the aromatase (CYP19). 5-Diol binds and activates estrogen receptors, but with lower affinity than E2 [19]. As depicted in Figures ​Figures11 and ​and3,3, sulfonation of E2 forms inactive estradiol sulfate (E2S), which can be reactivated following Inhibitors,research,lifescience,medical removal of the sulfate by the cytosolic estrogen sulfatase STS. Sulfate (SO42−) is obtained from the diet and the intracellular metabolism of sulfur-containing amino acids, including methionine and cysteine, and second is an important nutrient for human growth and development. Figure 3 Conjugation of estrone (E1) with sulfate by the estrogen sulfotransferases (SULT) results in the formation of inactive estrone sulfate (E1S). Sulfated estrone is reactivated by the steroid sulfatase (STS) which catalyzes the removal of sulphate, forming … The sulfuryl group donor (cosubstrate) for the SULT-catalyzed reaction to add the sulfate moiety to hydroxyl groups is 3′-phosphoadenosine 5′-phosphosulfate (PAPS). The reaction products are sulfated estrogens and adenosine 3′, 5′-diphosphate (PAP). PAPS is generated by PAPS-synthesizing enzymes (PAPSS).