Transport of vitamin D metabolites.

Vitamin D and its metabolites are bound to an alpha globulin (DBP) in human serum. This carrier protein binds 25-OHD and 24,25(OH)2D with higher affinity than vitamin D or 1,25(OH)2D, but the binding is highly specific for the vitamin D structure. The carrier mechanism appears to be unique in that it is a high affinity and high capacity system, capable of binding as much as 120,000 IU of biological activity per liter of plasma. DBP is apparently identical to group-specific component, and a DBP-deficient state has not been identified among approximately 75,000 human sera examined thus far. The liver appears to be the site for synthesis of DBP, and serum DBP levels are increased during pregnancy and during estrogen-progesterone therapy. However, in a variety of disorders of mineral homeostasis, serum DBP levels are normal. Two tissue binding proteins for vitamin D metabolites have been identified. One protein, sedimenting at 5-6S, has been found in all nucleated tissues, and exhibits a ligand preference similar to DBP. This tissue binding protein appears to be a complex of serum DBP with a tissue protein which is heat-labile, and which shows no capacity for binding vitamin D sterols. The physiologic role, if any, for this complex of serum DBP and tissue protein is not presently understood. The other tissue binding component is a 3-4S protein found only in recognized target tissues, and which shows a high binding affinity and specificity for 1,25(OH)2 D. It appears to be the receptor in the receptor-1,25(OH)2D migration to the nucleus, leading to the biosynthesis of mRNA which codes for products which affect calcium and phosphorus transport in target tissues.