Glucuronidation and sulfation of the tea flavonoid (-)-epicatechin by the human and rat enzymes
Glucuronidation and sulfation of the tea flavonoid (-)-epicatechin by the human and rat enzymes
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DOI：
10.1124/dmd.30.8.897
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发表时间：
2002-08-01
影响因子：
3.9
通讯作者：
Walle, T
中科院分区：
文献类型：
--
作者：
Vaidyanathan, JB;Walle, T
(-)-表儿茶素（EC）是存在于绿色茶中的类黄酮之一，被认为具有癌症的化学预防特性。然而，它的生物利用度并不清楚。在本研究中，我们确定了EC的代谢，专注于其葡萄糖醛酸和硫酸共轭使用人肝和肠微粒体和胞质溶胶以及重组UDP-葡萄糖醛酸转移酶（UGT）和磺基转移酶（SULT）的异构体相比，发生在大鼠。令人惊讶的是，EC不被人肝脏和小肠微粒体葡萄糖醛酸化。也没有人结肠微粒体或重组UGT 1A 7（不存在于肝脏或肠道中）葡萄糖醛酸化的证据。有趣的是，在大鼠肝微粒体中，EC有效地葡萄糖醛酸化，形成两个葡萄糖醛酸苷。相比之下，人肝胞质溶胶主要通过SULT 1A 1亚型有效地硫酸化EC。对于肠道，SULT 1A 1和SULT 1A 3都有贡献。其他SULT亚型的贡献很小。硫酸盐结合物的高效液相色谱显示所有组织的一个主要硫酸酯酶敏感峰。肝脏和肠胞质溶胶以及SULT 1A 1形成了额外的次要硫酸酯酶抗性峰，但Caco-2胞质溶胶和SULT 1A 3没有形成。在大鼠中，EC硫酸化的效率大大低于人类肝脏。这些结果表明，硫酸化是EC在人体肝脏和肠道中代谢的主要途径，没有发生葡萄糖醛酸化。大鼠和人类之间EC的葡萄糖醛酸化和硫酸化也存在很大的种属差异。
(-)- Epicatechin (EC) is one of the flavonoids present in green tea, suggested to have chemopreventive properties in cancer. However, its bioavailability is not clearly understood. In the present study, we determined the metabolism of EC, focusing on its glucuronic acid and sulfate conjugation using human liver and intestinal microsomes and cytosol as well as recombinant UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) isoforms in comparison with that occurring in the rat. Surprisingly, EC was not glucuronidated by the human liver and small intestinal microsomes. There was also no evidence of glucuronidation by human colon microsomes or by recombinant UGT1A7, which is not present in the liver or intestine. Interestingly, in the rat liver microsomes EC was efficiently glucuronidated with the formation of two glucuronides. In contrast, the human liver cytosol efficiently sulfated EC mainly through the SULT1A1 isoform. For the intestine, both SULT1A1 and SULT1A3 contributed. Other SULT isoforms contributed little. High-performance liquid chromatography of the sulfate conjugates showed one major sulfatase- sensitive peak with all tissues. An additional minor sulfatase- resistant peak was formed by the liver and intestinal cytosol as well as with SULT1A1 but not by the Caco-2 cytosol and SULT1A3. In the rat, EC sulfation was considerably less efficient than in the human liver. These results indicate that sulfation is the major pathway in EC metabolism in the human liver and intestine with no glucuronidation occurring. There was also a large species difference both in glucuronidation and sulfation of EC between rats and humans.