Human Plasma Transport of Vitamin D after Its Endogenous Synthesis

Department of Medicine, University of Pennsylvania, Philadelphia 19104.
Journal of Clinical Investigation (Impact Factor: 13.22). 06/1993; 91(6):2552-5. DOI: 10.1172/JCI116492
Source: PubMed

ABSTRACT Transport of vitamin D3 from its sites of cutaneous synthesis into the circulation has been assumed to be via the plasma vitamin D binding protein (DBP). We studied vitamin D transport from the skin in seven healthy volunteers who received whole body irradiation with 27 mJ/cm2 dosage of ultraviolet B light (290-320 nm). Samples of venous blood were collected serially in EDTA and immediately chilled. In KBr, plasma samples were ultracentrifuged to provide a rapid separation of proteins of density < and > 1.3 g/ml. Upper and lower phases and serial fractions were analyzed for vitamin D3 (extraction, HPLC), cholesterol (enzyme assay), and human DBP (hDBP) (radial immunodiffusion). Total plasma vitamin D (basal level < 1 ng/ml) increased by 10 h and peaked at 24 h (9 +/- 1 ng/ml). 98% of the D3 remained at the density > 1.3 layers for up to 7 d, whereas cholesterol (> 85%) was detected at density < 1.3 and all of the hDBP was at density > 1.3. In three volunteers who each ingested 1.25 mg of vitamin D2, the total plasma D2 increased to 90 +/- 32 ng/ml by 4 h, and the D2 was evenly distributed between the upper and lower layers at 4, 8, and 24 h after the dose, indicating a continuing association of the vitamin with chylomicrons and lipoproteins, as well as with hDBP. Actin affinity chromatography removed D3 from plasma of irradiated subjects, indicating the association of the D3 with DBP. These findings indicate that endogenously synthesized vitamin D3 travels in plasma almost exclusively on DBP, providing for a slower hepatic delivery of the vitamin D and the more sustained increase in plasma 25-hydroxycholecalciferol observed after depot, parenteral administration of vitamin D. In contrast, the association of orally administered vitamin D with chylomicrons and lipoproteins allows for receptor-mediated, rapid hepatic delivery of vitamin D, and the reported rapid but less-sustained increases in plasma 25-hydroxycholecalciferol.

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Available from: Bruce W Hollis, May 13, 2014
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    • "It circulates at a high concentration in the serum (6–7 μM), being part of the albumin gene family and sharing the multiple disulfide linked triple domain structure of albumin [7]. VDBP plays pivotal roles in multiple biological and metabolic pathways, such as the organ-specific transport of vitamin D and its metabolites to target organs [8]. VDBP binds both the inactive and the active form of Vitamin D obtained after enzymatic hydroxylation in the liver and kidney [9]. "
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    Journal of proteomics 05/2015; DOI:10.1016/j.jprot.2015.05.004 · 3.89 Impact Factor
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    • "The two KR-ratio regions for DBP are largely separated by species phylogeny (not shown). One complication that arises with DBP is the balance between the normal circulating vitamin D transport role and transport of vitamin D from the epidermis50 in those species for which synthesis in the skin is a major contributor to the vitamin D pool. Possibly the bimodal KR-ratio distribution for DBP reflects this distinction. "
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    Molecular Pharmaceutics 11/2013; 11(1). DOI:10.1021/mp4004749 · 4.38 Impact Factor
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    • "We believe that this observation is the result of the interaction between various metabolic pathways that regulate 25(OH)D levels. Previous studies have shown that endogenously synthesized vitamin D3 is transferred almost completely by VDBP to liver and this transport is slow, leading to a more sustained plasma vitamin D3, compared to that from supplementation of vitamin D, which is delivered to the liver by non-VDBP carriers in the plasma [40]. VDBP may also be an important determinant of serum 25(OH)D concentration, particularly when dietary intake of vitamin D is low. "
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