Vitamin K-Dependent Formation of Bone Gla Protein (Osteocalcin) and Its Function

Abstract

This chapter discusses the vitamin K–dependent formation of bone γ-carboxyglutamic acid (Gla) protein (BGP, osteocalcin) and its function. The bone Gla protein (BGP, osteocalcin) is the best characterized noncollagenous bone protein. Characteristic chemical features are small size—typically 49 or 50 residues—and existence within the molecule of three residues of the vitamin K–dependent amino acid, Gla. BGP is among the most abundant noncollagenous bone proteins and appears to be a universal constituent of the skeleton and tooth dentin of all vertebrates. As its synthesis is regulated by 1,25-dihydroxyvitamin D3, it is likely that BGP plays a role in the action of this hormone on bone. BGP has been detected in the calcified tissues of all vertebrates examined to date. The molecular weights of calf and chicken BGP have been determined by sedimentation equilibrium centrifugation and are 5800 and 6500, respectively. Both molecular weight values agree well with those computed from the corresponding covalent structures. In contrast, the apparent molecular weight of BGP determined by gel filtration and by SDS-gel electrophoresis is about 12,000.