IN VIVO DISTRIBUTION AND BIODISCRIMINATION OF alpha-TOCOPHEROL STEREOISOMERS

在维生素E类似物中，α-生育酚具有最高的生物活性。α-生育酚分为天然的和合成的。后者被称为全消旋-α-生育酚和八种立体异构体的等摩尔混合物。本文研究了大鼠口服或静脉注射全消旋-α-生育酚后，α-生育酚立体异构体的生物识别和组织分布。在给予全外消旋-α-生育酚6周后，大鼠中测试的所有组织都富含2 R立体异构体和少量2S异构体。但是，到静脉内给予全外消旋-α-生育酚后24小时，仅在肝脏中主要为2S异构体，而除肝脏外的所有组织均主要为2 R异构体。为了了解如何区分体内全消旋-α-生育酚的立体异构体，我们尝试了在吸收过程中使用插管法进入淋巴管并培养Caco-2细胞作为吸收模型进行区分的可能性。这两种方法均表明，在吸收过程中不发生歧视现象。这一结果表明，极低密度脂蛋白在肝脏排泄入血过程中可能发生生物识别。此外，这些结果表明α-生育酚转移蛋白（α-TTP）的颗粒化仅存在于肝脏中。在α-生育酚和其他生育酚类似物的所有立体异构体中，该α-TTP与RRR-a-生育酚具有最高的亲和力。因此，我们得出结论，这种α-TTP是维生素E类似物和α-生育酚立体异构体的生物鉴别的关键物质。

Among vitamin E analogs alpha-tocopherol has the highest biological activity. alpha-Tocopherol divides into natural and synthetic ones. The latter is called to all-rac-alpha-tocopherol and the equimolar mixture of eight stereoisomers. We studied the biological discrimination and distribution in tissues of stereoisomers of alpha-tocopherol in vivo after oral or intravenous administrarion of all-rac-alpha-tocopherol to rats. After administration of all-rac-alpha-tocopherol for 6 weeks, all of tissues tested in rats were rich in 2R stereoisomers with a small amounts of 2S isomers. But, by 24 hours after intarvenous administration of all-rac-alpha-tocopherol 2S isomers were predominant only in liver, whereas all tissues except liver 2R isomers were predominant. To know how to discriminate steroisomers of all-rac-alpha-tocopherol in body we tried the possibility of discrimination during absorption process using canulation methods into lymphatic duct and cultured Caco-2 cells as a model of absorption. These two methods showed that no discrimination occured during absorption. Theseresults indicate the possibility of biodiscrimination to be occured in liver during to excrete very low density lipoprotein into blood. Also, these results suggested the particication of alpha-tocopherol transfer protein (alpha-TTP) to be present only in liver. This alpha-TTP has the highest affinity with RRR-alpha-tocopherol among all of stereoisomers of alpha-tocopherol and other tocopherol analogs. Therefore, we concluded that this alpha-TTP was a key substance for biodiscrimination of vitamin E analogs and alpha-tocopherol stereoisomers.