Molecular Mechanism of Vitamine E recycling in vivo.

α -生育酚是维生素E最具生物活性的形式，是一种脂溶性抗氧化剂，可以保护细胞膜免受氧化应激。维生素E在自然界中有八种不同的形式，但与其他形式相比，动物体内富含α -生育酚。对动物和人体内维生素E转运的研究表明，肝脏在α -生育酚的优先保留和随后向组织的分布中起着关键作用，但对其机制知之甚少。α -生育酚转移蛋白（α - ttp）是一种对α -生育酚具有高度特异性结合能力的细胞质肝蛋白。在体外，α - ttp也具有在膜间运输α -生育酚的能力。我们成功地从大鼠肝脏中纯化了该蛋白，并从大鼠和人体内分离了其cDNA。此外，我们已经证明编码α - ttp的基因突变导致家族性维生素E缺乏症的共济失调。此病患者血清α -生育酚浓度低或检测不到，伴有进行性脊髓小脑功能障碍。在这些患者中，从肠道吸收α -生育酚并运输到肝脏是正常的，但他们将α -生育酚纳入肝脏VLDL的能力受损。从这些观察中发现，α - ttp催化肝脏吸收的α -生育酚转移到新生的VLDL。

Alpha-tocopherol, the most biologcally active form of vitamin E,is a lipid soluble antioxidant that protects membranes from oxidative stresses. Vitamin E occurs in nature in eight different forms, but animal body is enriched in alpha-tocopherol compared with other forms. Studies on the transport vitamin E in animals and man suggest that the liver plays a key role in the preferential retention, and subsequent distribution of alpha-tocopherol to tissues, but little was known about the mechanism. Alpha-tocopherol transfer protein (alpha-TTP) is a cytosolic liver protein with highly specific binding ability for alpha-tocopherol. Alpha-TTP also has an ability to transport alpha-tocopherol between membranes in vitro. We have succeeded in purifying this protein from rat liver and isolating its cDNA from rat and human. Furthermore, we have demonstrated that the mutations in the gene that encodes alpha-TTP cause ataxia with familial vitamin E deficiecy. Patients with this disease have low or undetectable serum alpha-tocopherol concentrations and progressive spinocerebellar dysfunction. In these patients, the absorption of alpha-tocopherol from intestine and the transport to the liver is normal, but they have an impaired ability to incorporate alpha-tocopherol into VLDL in the liver. From these observation, it was found that alpha-TTP catalyze the transfer of alpha-tocopherol taken up by the liver into nascent VLDL.