ReviewBiological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism
Introduction
The vitamin D binding protein (DBP), formerly known as group-specific component of serum (Gc-globulin), is the major plasma carrier protein of vitamin D and its metabolites. Vitamin D sterols are necessary to maintain a normal serum calcium concentration and electrolyte homeostasis.
DBP is a member of the albumin, α-fetoprotein and α-albumin/afamin gene family. It is a highly polymorphic serum protein, predominantly synthesized in the liver as a single chain of glycoproteins with a molecular weight of 52–59 kDa. Apart from its specific sterol binding capacity, DBP exerts several other important biological functions, from actin scavenging to fatty acid transport and macrophage activation. DBP is involved in macrophage chemotaxis and may play a role in bone density. In this review, biological and clinical aspects of DBP will be discussed. Special interest has risen in the use of DBP as a marker for trauma, based on the actin scavenging properties of DBP.
Section snippets
Structure, synthesis, turnover
DBP is a serum α2-globulin with a molecular weight of 52–59 kDa [1], [2]. The human DBP-gene is localized on the long arm of chromosome 4 (4q12–q13) (Fig. 1). It extends over 35 kb DNA and contains 13 exons and 12 introns. The amino acid sequence is composed of 458 amino acids, arranged in three domains, in addition to a 16 amino acid leader sequence [1], [3], [4]. Two binding regions have been identified within the DBP-sequence: a vitamin D binding domain between residues 35 and 49 and an
Vitamin D binding
The major function of DBP is binding, solubilization and transport of vitamin D and its metabolites [25]. Each DBP-vitamin D metabolite complex has its own affinity constant. 25(OH)-vitamin D3 (calcidiol) binds DBP (88% bound) with high affinity (Ka = 5 × 10− 8 M), whereas 1,25(OH)2-vitamin D3 (calcitriol), the most active metabolite of vitamin D, is bound (85%) with a lower affinity (Ka = 4 × 10− 7 M) [5]. Unlike other hydrophobic hormone-carrier proteins in human plasma, DBP has a high plasma
Clinical aspects
Many researchers have made attempts to link the expression of the DBP-alleles with susceptibility or resistance to disease.
Conclusion
DBP has recently received increasing attention. DBP is recognized as a member of a multigene family that includes albumin, α-fetoprotein and α-albumin/afamin. This highly polymorphic serum protein exhibits a geographical distribution with several exotic alleles, resulting in numerous phenotypes.
DBP is synthesized in liver as a single polypeptide and exhibits multifunctional properties. Besides the transport of vitamin D-metabolites, DBP binds G-actin with high-affinity and sequesters monomeric
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