Transport of vitamin D sterols in human plasma: effect of excess vitamin D, 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D
Transport of vitamin D sterols in human plasma: effect of excess vitamin D, 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D
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维生素 D 甾醇在人血浆中的转运：过量维生素 D、25 羟基维生素 D 和 1,25 二羟基维生素 D 的影响
DOI：
10.1111/j.1365-2362.1979.tb00908.x
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发表时间：
1979
影响因子：
5.5
通讯作者：
M. Fainaru
中科院分区：
文献类型：
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作者：
J. Silver;M. Fainaru
摘要。维生素D及其更活跃的代谢物，25羟基维生素D（25‐OH‐D）和1,25‐二羟基维生素D(1,25‐（OH）2‐D)，在人血浆中通过特定的结合蛋白（DBP）运输，DBP已被证明具有α‐球蛋白的电泳流动性。由于正常人血浆中DBP的浓度约为5 μmol/l，而所有维生素D代谢物的浓度均小于0.2 μmol/l，因此在生理条件下DBP的饱和浓度小于3%。我们研究了上述代谢物在体外正常浓度和饱和浓度下在人血浆中的转运。将人血浆与越来越多的维生素D代谢物及其放射性标记示踪剂一起培养。采用超离心分离血浆脂蛋白（密度，d < 1·21 g/ml），无脂蛋白血浆琼脂糖凝胶电泳（密度，d < 1·21 g/ml）分离α球蛋白（DBP）和白蛋白。该示踪剂在血浆蛋白中的回收率均在80%以上。在生理浓度下，[3H]25‐OH‐D几乎完全与DBP结合（98%），[3H]维生素D或[14C]维生素D既与DBP结合又与脂蛋白结合（40%），[3H] 125‐（OH）2‐D与DBP结合（62%），与脂蛋白结合（15%），也与白蛋白结合（23%）。随着维生素D代谢物浓度的增加，舒张压趋于饱和。DBP对所有三种甾醇的结合能力相似，约为5 μmol/l血浆，或每摩尔蛋白质1摩尔甾醇，但三种甾醇（维生素D > 1,25‐（OH）2‐D > 25‐OH‐D）的饱和浓度不同。25‐OH‐D对DBP具有最大的亲和力，并且在较高浓度下完全取代DBP中的维生素D和125 (OH)2‐D。所有甾醇都与血浆脂蛋白和白蛋白结合：维生素D优先与脂蛋白结合，25 - OH - D和125 - (OH)2 - D与白蛋白结合。我们之前在一名维生素D中毒儿童的血浆中观察到类似的维生素D结合模式。维生素D与脂蛋白，特别是白蛋白结合的增加可能有助于解释维生素D过多症毒性的发病机制，其中更活跃的代谢物的血浆水平不足以解释临床症状。
Abstract. Vitamin D and its more active metabolites, 25 hydroxyvitamin D (25‐OH‐D) and 1,25‐dihydroxy‐vitamin D (1,25‐(OH)2‐D), are transported in human plasma on a specific binding protein (DBP), which has been shown to have an α‐globulin electrophoretic mobility. Since the concentration of DBP in normal human plasma is approximately 5 μmol/l, whereas that of all the vitamin D metabolites is less than 0·2 μmol/l, DBP is less than 3% saturated under physiological conditions. We have studied the transport of the above‐mentioned metabolites in human plasma in vitro at normal and saturating concentrations. Human plasma was incubated with increasing amounts of vitamin D metabolites together with their radiolabelled tracers. Ultracentrifugation was used to isolate plasma lipoproteins (density, d < 1·21 g/ml) and agarose gel electrophoresis of lipoprotein‐free plasma (d > 1·21 g/ml) to separate DBP (α globulin) from albumin. The recovery of the tracer in plasma proteins was always more than 80%. At physiological concentrations [3H]25‐OH‐D bound almost exclusively to DBP (98%), [3H]vitamin D or [14C]vitamin D bound both to DBP and to lipoproteins (40%), and [3H]1,25‐(OH)2‐D bound to DBP (62%), to lipoproteins (15%) and also to albumin (23%). When the concentration of vitamin D metabolites was increased, DBP became saturated. The binding capacity of DBP was similar for all three sterols, about 5 μmol/l plasma, or one mole of sterol per mole of protein, but the saturating concentration was different for the three sterols (vitamin D > 1,25‐(OH)2‐D > 25‐OH‐D). 25‐OH‐D had the greatest affinity for DBP, and it completely displaced both vitamin D and 1,25(OH)2‐D from DBP at higher concentrations. All sterols bound to both plasma lipoproteins and albumin: vitamin D preferentially to lipoproteins and both 25‐OH‐D and 1,25‐(OH)2‐D to albumin. A similar binding pattern for vitamin D in plasma was observed previously by us in a child with vitamin D toxicity. The increased binding of vitamin D to lipoproteins and especially to albumin may help explain the pathogenesis of toxicity in hypervitaminosis D, where the plasma levels of the more active metabolites are insufficient to account for the clinical signs.
维生素 D 结合蛋白。
影响因子：
--
作者：
HaddadJr,JG
通讯作者：
HaddadJr,JG