Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs

Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs
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DOI:
10.1016/s0014-5793(97)00499-7
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发表时间:
1997-06-02
期刊:
影响因子:
3.5
通讯作者:
Inoue, K
Inoue, K
中科院分区:
生物学3区
文献类型:
--
作者:
Hosomi, A;Arita, M;Inoue, K

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α-生育酚转移蛋白(α-TTP)是导致家族性维生素E缺乏症的基因产物,在测定血浆维生素E水平中起着重要作用。我们研究了α-TTP识别所需的维生素E类似物的结构特征。通过评估非标记维生素E类似物和α-[H-3]生育酚在体外膜间转移的竞争来评估配体的特异性。根据竞争程度计算的相对亲和力(RRR-α-生育酚=100%)如下:β-生育酚,38%;γ-生育酚,9%;β-生育酚,2%;α-生育酚醋酸酯,2%;α-生育酚醌,2%;SRR-α-生育酚,11%;α-生育三烯酚,12%;曲洛克斯,9%。有趣的是,相对亲和力与从大鼠吸收-妊娠试验中获得的已知生物活性之间存在线性关系。从这些观察中,我们得出结论,维生素E类似物对α-TTP的亲和力是其生物活性的关键决定因素之一。(C)1997年欧洲生化学会联合会。
alpha-Tocopherol transfer protein (alpha TTP), a product of the gene which causes familial isolated vitamin E deficiency, plays an important role in determining the plasma vitamin E level. We examined the structural characteristics of vitamin E analogs required for recognition by alpha TTP. Ligand specificity was assessed by evaluating the competition of non-labeled vitamin E analogs and alpha-[H-3]tocopherol for transfer between membranes in vitro. Relative affinities (RRR-alpha-tocopherol=100%) calculated from the degree of competition were as follows: beta-tocopherol, 38%; gamma-tocopherol, 9%; delta-tocopherol, 2%; alpha-tocopherol acetate, 2%; alpha-tocopherol quinone, 2%; SRR-alpha-tocopherol, 11%; alpha-tocotrienol, 12%; trolox, 9%. Interestingly, there was a linear relationship between the relative affinity and the known biological activity obtained from the rat resorption-gestation assay. From these observations, we conclude that the affinity of vitamin E analogs for alpha TTP is one of the critical determinants of their biological activity. (C) 1997 Federation of European Biochemical Societies.