Gamma-carboxyglutamic acid

Furie, B., Bouchard, B.A. andFurie, B.C. (1999) Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid. Blood, 93 (6), 1798-1808. 

Kelleher, N.L., Zubarev, R.A., Bush, K., Eurie, B., Eurie, B.C., McLafferty, E.W. and Walsh, C.T. (1999) Localization of labile posttranslational modifications by electron capture dissociation the case of gamma-carboxyglutamic acid. Analytical Chemistry, 71, 4250-4253. 

Coumarins are competitive inhibitors of vitamin K, which is required for the formation in the liver of the amino acid, gamma-carboxyglutamic acid. This is necessary for the synthesis of prothrombin and factors VII, IX and X (Figure 17.1). After starting treatment the anticoagulant effect is delayed until the concentration of normal coagulation factors falls (36-72 h). The effects can be reversed by vitamin K (slow maximum effect only after 3-6 h) or by whole blood or plasma (fast). Gut bacteria synthesise vitamin K and thus are an important source of this vitamin. Consequently, antibiotics can cause excessive prolongation of the prothrombin time in patients otherwise adequately controlled on warfarin. 

The coagulation and anticoagulation proteases, factors VII, IX, and X, and protein C, have a common domain structure with an N-terminal gamma-carboxyglutamic acid (Gla)-containing domain that is followed by two EGF-like modules, whereas the C-terminal half of each protein is occupied by a trypsin-like serine protease domain. Prothrombin also has an N-terminal Gla domain and a C-terminal serine protease... 

C6H9N06 L-gamma-carboxyglutamic acid 53861-57-7 25.00 1.3721 2 7846 C6H10O2 methyl 3-methyl-2-butenoate 924-50-5 20.00 0.9337 1... 

Haroon Y. Rapid assay for gamma-carboxyglutamic acid in urine and bone by precolumn derivatization and reversed-phase liquid chromatography. Anal Biochem 1984 140 343-8. 

Sokoll LJ, Booth SL, O Brien ME, Davidson KW, Tsaioun KI, Sadowski JA. Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects. Am J Clin Nutr 1997 65 779-84. 

Catherwood BD, Marcus R, Madvig P, Cheung AK. Determinants of bone gamma-carboxyglutamic acid-containing protein in plasma of healthy aging subjects. Bone 1985 6 9-13. 

Li, L., Darden, T. A., Freedman, S. J., Furie, B. C., Furie, B., Baleja, J. D., Smith, H., Hiskey, R. G. Pedersen, L. G. (1997). Refinement of the NMR solution structure of the gamma-carboxyglutamic acid domain of coagulation factor IX using molecular dynamics simulation with initial Ca2+ positions determined by a genetic algorithm. Biochemistry 36(8), 2132-8. 

Osteocalcin (OCN) is one of the most prevalent non-collagenous intraosseous proteins, and it is predominantly localized to osteoblasts. This 9-kD cytoplasmic protein contains abundant gamma carboxyglutamic acid residues. Its expression is down-regulated by helix-loop-helix-type transcription factors and up-regulated by vitamin D analogs such as 1,25 dihydroxyvita-min D2 and 24-epi-l,25 dihydroxyvitamin D2 in the final steps of osteoblastic differentiation and osteoid formation. ... 

Price, P.A., Urist, M.R., Otawara, Y. (1983) Matrix Gla protein, a new gamma-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone. Biochemical and Biophysical Research Communications, 117, 765-771. 

Stenflo, J., 1978. Vitamin K, prothrombin, and gamma-carboxyglutamic acid. Adv. Enzymol. Relat. Areas Mol. Biol. 46,1-31. 

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