The physiologic significance of plasma transport of vitamin D and metabolites

Vitamin D and its metabolites do not circulate free but are bound to specific plasma transport proteins that solubilize them and protect them from oxidative inactivation. A specific vitamin D transport protein has been demonstrated in man, rat and chick; it preferentially binds 25-hydroxyvitamin D (25-(OH)D), the major active form of the vitamin in the circulation. The binding of vitamin D and its analogs by the D/25-(OH)D transport protein from rat plasma involves recognition of structural properties and steric configuration of both the single ring and the side chain. The C-25 hydroxyl group plus the vitamin D₃ configuration of both the side chain and the single ring maximize the binding. Although the binding of vitamin D₂ and its analogs by human and rat D/25-(OH)D transport protein is roughly equivalent to that of vitamin D₃ and its analogs, abnormal plasma binding of vitamin D₂ and 25-(OH)D₂ by the D/25-(OH)D transport protein in chick plasma may play an important role in the increased metabolic inactivation of these compounds and the resultant decreased antirachitic potency of vitamin D₂ in the chick. Preliminary studies suggest that 1,25-(OH)₂D is carried by the D/25-(OH)D transport protein in rat plasma but that a specific dihydroxy transport protein also exists in human plasma. These studies suggest that transport proteins play an important role in the facilitation of vitamin D transport and normal vitamin D metabolism.