Sulfation of environmental estrogen-like chemicals by human cytosolic sulfotransferases

硫酸盐结合是体内外源性物质或内源性化合物（如类固醇和甲状腺激素、儿茶酚胺和胆汁酸）生物转化和/或排泄的主要途径。负责的酶，即所谓的“胞质磺基转移酶”，催化磺酸根基团从活性硫酸根，3 '-磷酸腺苷5'-磷酸硫酸根（PAPS）转移到含有羟基或氨基的底物化合物。一般认为硫酸化可以增加异生物质或内源性化合物的水溶性，并促进它们从体内的去除。在本项目中，为了研究硫酸化（体内主要的II期解毒途径）是否可以用作环境雌激素的灭活/处置的手段，制备重组人胞质磺基转移酶并测试其与双酚A的酶活性，己烯雌酚、4-辛基酚、4-壬基酚和17 α-乙炔基酚为底物 ...更多信息 es.在检查的七种重组酶中，只有SULT 1C磺基转移酶#1对测试的环境雌激素没有显示出活性。在其他六种磺基转移酶中，简单的酚（P）形式的酚磺基转移酶和雌激素磺基转移酶似乎对环境雌激素比其他四种磺基转移酶更活跃。代谢标记实验揭示了环境雌激素的硫酸化及其硫酸化衍生物由HepG 2人肝癌细胞释放。此外，硫酸化环境雌激素似乎不能穿透HepG 2细胞膜。本项目研究所取得的结果清楚地表明，环境雌激素发生了硫酸化。硫酸化环境雌激素未能穿透HepG 2细胞膜可能意味着硫酸化作为一种有用的机制，用于去除这些有害化合物。更多的研究是必要的，以充分了解参与不同的磺基转移酶在体内的环境雌激素的灭活/去除。少

Sulfate conjugation represents a major pathway in vivo for the biotransformation and/or excretion of xenobiotics or endogenous compounds such as steroid and thyroid hormones, catecholamines, and bile acids. The responsible enzymes, so-called "cytosolic sulfotransferases," catalyze the transfer of a sulfonate group from the active sulfate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), to a substrate compound containing either a hydroxyl or an amino group. It is generally believed that sulfation may increase the water-solubility of xenobiotic or endogenous compounds and facilitate their removal from the body.In this project, to investigate whether sulfation, a major Phase II detoxification pathway in vivo, can be employed as a means for the inactivation/disposal of environmental estrogens, recombinant human cytosolic sulfotransferases were prepared and tested for enzymatic activities with bisphenol A, diethylstilbestrol, 4-octylphenol, 4-nonylphenol, and 17 α-ethynylestradiol as substrat … More es. Of the seven recombinant enzymes examined, only SULT1C sulfotransferase #1 showed no activities toward the environmental estrogens tested. Among the other six sulfotransferases, the simple phenol (P)-form phenol sulfotransferase and estrogen sulfotransferase appeared to be considerably more active toward environmental estrogens than the other four sulfotransferases. Metabolic labeling experiments revealed the sulfation of environmental estrogens and the release of their sulfated derivatives by HepG2 human hepatoma cells. Moreover, sulfated environmental estrogens appeared to be incapable of penetrating through the HepG2 cell membrane. The results obtained in this project study showed clearly the occurrence of the sulfation of environmental estrogens. That the sulfated environmental estrogens failed to penetrate through the HepG2 cell membrane may imply sulfation as a useful mechanism for the removal of these hazardous compounds. More studies are warranted in order to fully appreciate the involvement of different sulfotransferases in the inactivation/removal of environmental estrogens in vivo. Less