Vitamin D Binding Protein (Gc-Globulin)*

Abstract

UNLIKE other hydrophobic hormone-binding systems in mammalian plasma, the binding protein for vitamin D and its metabolites circulates in remarkably higher titer (5 × 10−6 M) compared to its major circulating ligand 25-hydroxycholecalciferol (25-OHD3) (5 × 10−8 M), and displays a rapid turnover rate (1) (see Table 1). Initially characterized as group-specific component or Gc-globulin, its identity with the plasma vitamin D binding protein (DBP) was discovered in 1975 (2). This hepatic protein has a strong homology with serum albumin (ALB) and α-fetoprotein (AFP) (3, 4). Although many thousands of sera have been tested, deletion or gross alteration of the DBP gene has not been detected, lending support to the notion that such mutations might be lethal. Since analbuminemia and abnormalities of other plasma binding proteins do not appear to cause disease (5–7), DBP activities are presumably vital. In recent years, new observations on the structure, origin, associations, and activities of DBP have been made. It is the purpose of this paper to review these findings and provide an update of recent developments in our understanding of this protein and its functions.