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。-生育酚分为天然的和合成的。后者被称为全rac- α -生育酚和八个立体异构体的等摩尔混合物。研究了大鼠口服或静脉注射α -生育酚后α -生育酚立体异构体在体内的生物鉴别和组织分布。全rac- α -生育酚给药6周后，各组大鼠组织中均含有丰富的2R立体异构体和少量的2S立体异构体。但在静脉给药24小时后，全rac- α -生育酚2S异构体仅在肝脏中占优势，而除肝脏外的所有组织中均有2R异构体占优势。为了了解如何在体内识别全rac- α -生育酚的甾体异构体，我们尝试了在吸收过程中识别的可能性，采用试管法进入淋巴管，培养Caco-2细胞作为吸收模型。结果表明，两种方法在吸收过程中均无明显区别。提示极低密度脂蛋白排泄入血过程中，肝脏可能发生生物歧视。此外，这些结果表明α -生育酚转移蛋白（α - ttp）的颗粒只存在于肝脏。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 - α -生育酚的亲和性最高。因此，我们认为该α - ttp是生物鉴别维生素E类似物和α -生育酚立体异构体的关键物质。

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.