Zamierowski M M, Wagner C
J Biol Chem. 1977 Feb 10;252(3):933-8.
Intraperitoneal injection of tritiated folic acid (PteGlu) into rats has revealed the presence of three separate protein fractions in the cytosol fraction of the liver and one in the mitochondria which bind folate derivatives. The proteins in the cytosol (cytosol I, II and III) have approximate molecular weights of 350,000, 150,000, and 25,000 and the protein in the mitochondria has an approximate molecular weight of 90,000 as estimated by gel filtration. The bound folate derivatives are primarily polyglutamate forms while cytosol II contains primarily bound 5-methyltetrahydrofolate polyglutamate derivatives. Little binding of radioactively labeled folic acid or 5-methyltetrahydrofolate to these fractions was observed when binding was carried out in vitro. Significant binding in vitro was observed, however, when a mixture of biosynthetically labeled natural folate derivatives was used. These proteins have not been purified, but cytosol III partially consists of the enzyme, tetrahydrofolate dehydrogenase (EC 1.5.1.3). Studies on the time course of folic acid incorporation into the liver showed that soon after injection nonmetabolized folic acid was bound to the plasma membrane fraction of the liver cell. It is suggested that at least one of the binding proteins in the cytosol may be involved in storage of the vitamin while the binding of nonmetabolized folic acid to the plasma membrane may reflect the existence of a carrier for folic acid transport into the cell.
向大鼠腹腔注射氚标记的叶酸（蝶酰谷氨酸）后发现，肝脏细胞溶质部分存在三种不同的蛋白质组分，线粒体中有一种蛋白质组分可结合叶酸衍生物。通过凝胶过滤估计，细胞溶质中的蛋白质（细胞溶质I、II和III）的分子量约为350,000、150,000和25,000，线粒体中的蛋白质分子量约为90,000。结合的叶酸衍生物主要是多聚谷氨酸形式，而细胞溶质II主要含有结合的5-甲基四氢叶酸多聚谷氨酸衍生物。体外进行结合时，未观察到放射性标记的叶酸或5-甲基四氢叶酸与这些组分的明显结合。然而，当使用生物合成标记的天然叶酸衍生物混合物时，体外观察到了明显的结合。这些蛋白质尚未纯化，但细胞溶质III部分由四氢叶酸脱氢酶（EC 1.5.1.3）组成。对叶酸掺入肝脏的时间进程研究表明，注射后不久，未代谢的叶酸与肝细胞的质膜部分结合。有人提出，细胞溶质中的至少一种结合蛋白可能参与维生素的储存，而未代谢的叶酸与质膜的结合可能反映了存在一种将叶酸转运到细胞内的载体。
