a Center for Pharmacogenetics and Department of Pharmaceutical Sciences , University of Pittsburgh , Pittsburgh , PA , USA.
b Department of Endocrinology and Metabolic Disease , The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou , China.
Expert Opin Drug Metab Toxicol. 2019 Apr;15(4):329-339. doi: 10.1080/17425255.2019.1588884. Epub 2019 Mar 18.
Biotransformation is important in the metabolism of endobiotics and xenobiotics. This process comprises the activity of phase I and phase II enzymes. Estrogen sulfotransferase (SULT1E1 or EST) is a phase II conjugating enzyme that belongs to the family of cytosolic sulfotransferases. The expression of SULT1E1 can be detected in many tissues, including the liver. SULT1E1 catalyzes the transfer of a sulfate group from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to any available hydroxyl group in estrogenic molecules. The substrates of SULT1E1 include the endogenous and synthetic estrogens. Upon SULT1E1-mediated sulfation, the hydrosolubility of estrogens increases, preventing the binding between the sulfated estrogens and the estrogen receptor (ER). This sulfated state of the estrogens is not irreversible, as the steroid sulfatase (STS) can convert sulfoconjugated estrogens to free estrogens. The expression of SULT1E1 is inducible by several diseases that involve tissue inflammation, such as type 2 diabetes, sepsis, and ischemia-reperfusion injury. Areas covered: This systematic literature review aims to summarize the role of SULT1E1 in the metabolism of estrogenic drugs and xenobiotics, and the role of SULT1E1 in the pathogenesis of several diseases, including cancer, metabolic disease, sepsis, liver injury, and cystic fibrosis. Meanwhile, ablation or pharmacological inhibition of SULT1E1 can affect the outcomes of the aforementioned diseases. Expert opinion: In addition to its role in metabolizing estrogenic drugs, SULT1E1 is unexpectedly being unveiled as a mediator for the disease effect on estrogen metabolism and homeostasis. Meanwhile, because the expression and activity of SULT1E1 can affect the outcome of diseases, the same sulfotransferase and the reversing enzymes STS can be potential therapeutic targets to prevent or manage diseases. Accumulating evidence suggest that the physiological and pathophysiological effects of SULT1E1 can be estrogen-independent and it is necessary to elucidate what other possible substrates may be recognized by the enzyme. Moreover, human studies are paramount to confirm the human relevance of the animal studies.
生物转化在内源性和外源性物质的代谢中起着重要作用。这个过程包括了 I 相和 II 相酶的活性。雌激素硫酸转移酶（SULT1E1 或 EST）是一种 II 相结合酶，属于细胞溶质硫酸转移酶家族。SULT1E1 的表达可以在许多组织中检测到，包括肝脏。SULT1E1 催化 3'-磷酸腺苷-5'-磷酸硫酸（PAPS）中的硫酸根从任何可用的羟基转移到雌激素分子上。SULT1E1 的底物包括内源性和合成雌激素。在 SULT1E1 介导的硫酸化作用下，雌激素的亲水性增加，阻止了硫酸化雌激素与雌激素受体（ER）的结合。这种雌激素的硫酸化状态不是不可逆的，因为甾体硫酸酯酶（STS）可以将硫酸化的雌激素转化为游离的雌激素。SULT1E1 的表达可被几种涉及组织炎症的疾病诱导，如 2 型糖尿病、脓毒症和缺血再灌注损伤。涵盖领域：本系统文献综述旨在总结 SULT1E1 在雌激素药物和外源性物质代谢中的作用，以及 SULT1E1 在几种疾病发病机制中的作用，包括癌症、代谢性疾病、脓毒症、肝损伤和囊性纤维化。同时，SULT1E1 的消融或药理抑制可能会影响上述疾病的结局。专家意见：除了在代谢雌激素药物方面的作用外，SULT1E1 出人意料地被揭示为疾病对雌激素代谢和内稳态影响的介质。同时，由于 SULT1E1 的表达和活性会影响疾病的结局，相同的硫酸转移酶和反转酶 STS 可能是预防或管理疾病的潜在治疗靶点。越来越多的证据表明，SULT1E1 的生理和病理生理效应可能与雌激素无关，有必要阐明该酶可能识别的其他可能的底物。此外，人体研究对于证实动物研究的人类相关性至关重要。
