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Transport of vitamin D sterols in human plasma: effect of excess vitamin D, 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D
Author(s) -
SILVER JUSTIN,
FAINARU MENAHEM
Publication year - 1979
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1979.tb00908.x
Subject(s) - vitamin d binding protein , chemistry , albumin , vitamin d and neurology , vitamin , ergocalciferol , mole , cholecalciferol , blood proteins , human serum albumin , endocrinology , chromatography , serum albumin , medicine , biochemistry , biology
. 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 [ 3 H]25‐OH‐D bound almost exclusively to DBP (98%), [ 3 H]vitamin D or [ 14 C]vitamin D bound both to DBP and to lipoproteins (40%), and [ 3 H]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.