Radioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma.

The vitamin K-dependent protein of bone has been detected in human plasma by radioimmunoassay at 4.5 ng per ml. The plasma protein has the same apparent molecular weight as the pure bone Gla protein (BGP) and other studies indicate the plasma protein is probably the intact bone protein. BGP also has been detected in bovine serum by radioimmunoassay. The bovine serum levels of BGP decrease with developmental age from 200 ng per ml in fetal calves to 26 ng per ml in adult cows. The implications of the discovery of BGP in plasma to the function of this unique protein are discussed. This assay employs rabbit antibody directed against calf BGP and has a sensitivity of 0.1 ng. The antibody crossreacts with purified human BGP but not with BGP from rat or rabbit bone. Studies with peptides of known structure derived from enzymatic digests of BGP indicate that the rabbit antibody recognizes the COOH-terminal region of the 49-residue calf bone protein.