Gamma-carboxyglutamic acid: identification and distribution in vitamin K-dependent proteins
Nelsestuen, G.L.; Zytkovicz, T.H.; Howard, J.B.
Mayo Clinic Proceedings 49(12): 941-944
1974
ISSN/ISBN: 0025-6196 PMID: 4444341 Document Number: 74483
gamma -Carboxyglutamic acid was shown to be a component of prothrombin and to reside in a peptide which contains some of the vitamin K-dependent sites in prothrombin. The vitamin is required for the incorporation of the second carboxyl group on to the glutamic acid side chain. The vitamin K-dependent sites, and hence gamma -carboxyglutamic acid, on prothrombin are responsible for calcium-binding, essential for the physiological conversion of prothrombin to thrombin, and for the adsorption of prothrombin on to precipitates of barium salts. There are at least 10 gamma -carboxyglutamic acid residues in prothrombin, all of which are in the nonthrombin region of the protein; bovine factor X contains at least 14 residues of gamma -carboxyglutamic acid. Reduction of the carboxyl groups of intact vitamin K-dependent proteins with diborane-3H followed by hydrolysis releases 5,5'-dihydroxyleucine, the reduction product of gamma -carboxyglutamic acid, which can be identified by amino acid analysis.