New perspectives on the vitamin D binding protein

Abstract

The serum vitamin D binding protein (DBP), also known as GC-globulin, is a multifunctional protein known for its role in the transport of vitamin D metabolites. DBP also binds fatty acids and actin monomers, preventing their polymerization that could be detrimental in the circulatory system. DBP may have immune functions independent of its role as a transporter of vitamin D. Because of the abundance of DBP, many aspects of its basic biochemistry were quickly established. Other features of vitamin D action, particularly transcriptional mechanisms of regulation, received greater focus and early interest in DBP centred on its value as a tool for population genetics because of its intriguing genetic variations. Nonetheless, knowledge of DBP mechanisms in physiology was obtained, and functions beyond vitamin D ligand binding were identified. With the recent increased attention regarding the benefits of vitamin D (bone health and immunological regulation), there has been a resurgence of interest in DBP. Because DBP is the primary transporter of vitamin D, it has a role in maintaining the total levels of vitamin D for the organism and in regulating the amounts of free (unbound) vitamin D available for specific tissues and cell types to utilize. This review will describe the findings on the basic biochemistry and molecular biology of DBP, the studies that elucidated its biological functions and highlight these results in light of the current renewed interest in vitamin D and human health, as well as the debate over what constitutes sufficient levels of vitamin D.

PKPD modelling to predict altered disposition of 1α,25‐dihydroxyvitamin D3 in mice due to dose‐dependent regulation of CYP27B1 on synthesis and CYP24A1 on degradation

“…Furthermore, fitted values of k12 and Vss increased with dose, suggesting a larger distribution volume with increasing dose levels. These distributional changes could not be explained by a saturation of protein binding sites as the 5 μM concentration of DBP in plasma (Chun, 2012) greatly exceeds the plasma 1,25(OH)2D3 concentrations from i.v. dosing.…”

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

“…Although DBP functions as a binding protein for all vitamin D metabolites in the serum [20 times less affinity for 1,25(OH) 2 D 3 than for 25(OH)D 3 ], DBP also sequesters actin, can bind fatty acids, and can function as a chemotactic factor with a significant role in neutrophil recruitment (87,453). In Dbp null mice, neutrophil recruitment has been reported to be impaired.…”

Plasma 25‐hydroxyvitamin D and the risk of breast cancer in the European prospective investigation into cancer and nutrition: A nested case–control study

“…35 As the vitamin D-binding protein has the functions of maintaining 25(OH)D levels and transporting 25(OH)D to target organs, 36 one may speculate that HRT users with high 25(OH)D levels benefit from an improved supply of the breast tissue with vitamin D. On the other hand, the bioavailability of 25(OH)D may rather depend on its free circulating fraction. 36,37 According to the "free hormone hypothesis," presumably higher levels of free 25(OH)D among HRT users with comparably high total 25(OH)D values may therefore be another explanation for our finding.…”