Carboxyglutamyl residue

Work in the mid-1970s demonstrated that the vitamin K-dependent step in prothrombin synthesis was the conversion of glutamyl residues to y-carboxyglutamyl residues. Subsequent studies more cleady defined the role of vitamin K in this conversion and have led to the current theory that the vitamin K-dependent carboxylation reaction is essentially a two-step process which first involves generation of a carbanion at the y-position of the glutamyl (Gla) residue. This event is coupled with the epoxidation of the reduced form of vitamin K and in a subsequent step, the carbanion is carboxylated (77—80). Studies have provided thermochemical confirmation for the mechanism of vitamin K and have shown the oxidation of vitamin KH2 (15) can produce a base of sufficient strength to deprotonate the y-position of the glutamate (81—83). 

Liska DJ and Suttie JW (1988) Location of gamma-carboxyglutamyl residues in partially carboxylated prothrombin preparations. Biochemistry 27, 8636 1. 

OC contains three specific glutamyl residues at amino acid positions 17, 21, and 24, which may be converted to y-carboxyglutamyl residues by a posttranslational, vitamin K-dependent enzymatic carboxylation. This unique car-boxylated amino acid binds calcium ions and is found in various proteins involved in blood coagulation and in calcium transport, deposition, and homeostasis. Undercar-boxylated OC, which has been reported in serum in some conditions, may be related to decreased bone density and may respond to administration of vitamin K. Although OC binds calcium and hydroxyapatite, its physiological role is unknown. 

Plasma or serum phylloquinone concentration Urinary y-carboxyglutamyl residues... 

Figure 49-25 Amino acid sequence of osteocalcin, A disulfide bond formed between cysteines in positions 23 and 29 stabilizes two anti parallel a-helica structures representing 40% of the overall structure.Three glutamyl residues at positions 17, 21, and 24 can be carboxyiated in a posttranslational, vitamin K-dependent, enzymatic step producing y-carboxyglutamyl (Gla) residues.

Brown, M.A., L.M. Stenberg, U. Persson, and J. Stenflo, Identification and purification of vitamin K-dependent proteins and peptides with monoclonal antibodies specific for gam-ma-carboxyglutamyl (Gla) residues. J. Biol. Chem., 2000, 275, 19795-19802. 

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