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. 1977 Jun;59(6):1151–1157. doi: 10.1172/JCI108739

The presence of protein-bound gamma-carboxyglutamic acid in calcium-containing renal calculi.

J B Lian, E L Prien Jr, M J Glimcher, P M Gallop
PMCID: PMC372328  PMID: 864007

Abstract

The amino acid gamma-carboxyglutamic acid (Gla) is found in four blood-clotting proteins, in a bone protein, in kidney protein, and in the protein present in various ectopic calcifications. This paper reports the presence of Gla in the EDTA-soluble, nondialyzable proteins of calcium-containing renal calculi including calcium oxalate, hydroxyapatite, and mixed stores of apatite and struvite (MgNH4PO4). Calculi composed of pure struvite and those composed of only uric acid or cystine do not contain Gla. From calcium oxalate and hydroxyapatite stontes, a protein of about 17,000 daltons was obtained which contained about 40 residues of Gla per 1,000 amino acids. The amino acid composition of this protein had no apparent relationship to the Gla-containing bone protein or to the similarly-sized F1 fragment of prothrombin which contains about 64 residues of Gla per 1,000 amino acid residues. The Gla-rich protein in calcium-containing renal stones thus may be a different Gla-containing protein. These data as well as other studies demonstrating the presence of Gla in pathologically calcified tissues not normally containing Gla suggest that the Gla-containing proteins may be of considerable pathophysiological significance.

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Selected References

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  1. Boyce W. H. Organic matrix of human urinary concretions. Am J Med. 1968 Nov;45(5):673–683. doi: 10.1016/0002-9343(68)90203-9. [DOI] [PubMed] [Google Scholar]
  2. Butler W. T., Finch J. E., Jr, Desteno C. V. Chemical character of proteins in rat incisors. Biochim Biophys Acta. 1972 Jan 26;257(1):167–171. doi: 10.1016/0005-2795(72)90266-8. [DOI] [PubMed] [Google Scholar]
  3. CAULFIELD J. B., SCHRAG P. E. ELECTRON MICROSCOPIC STUDY OF RENAL CALCIFICATION. Am J Pathol. 1964 Mar;44:365–381. [PMC free article] [PubMed] [Google Scholar]
  4. Esmon C. T., Sadowski J. A., Suttie J. W. A new carboxylation reaction. The vitamin K-dependent incorporation of H-14-CO3- into prothrombin. J Biol Chem. 1975 Jun 25;250(12):4744–4748. [PubMed] [Google Scholar]
  5. Esmon C. T., Suttie J. W., Jackson C. M. The functional significance of vitamin K action. Difference in phospholipid binding between normal and abnormal prothrombin. J Biol Chem. 1975 Jun 10;250(11):4095–4099. [PubMed] [Google Scholar]
  6. Hauschka P. V., Friedman P. A., Traverso H. P., Gallop P. M. Vitamin K-dependent gamma-carboxyglutamic acid formation by kidney microsomes in vitro. Biochem Biophys Res Commun. 1976 Aug 23;71(4):1207–1213. doi: 10.1016/0006-291x(76)90782-8. [DOI] [PubMed] [Google Scholar]
  7. Hauschka P. V., Lian J. B., Gallop P. M. Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3925–3929. doi: 10.1073/pnas.72.10.3925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lian J. B., Skinner M., Glimcher M. J., Gallop P. The presence of gamma-carboxyglutamic acid in the proteins associated with ectopic calcification. Biochem Biophys Res Commun. 1976 Nov 22;73(2):349–355. doi: 10.1016/0006-291x(76)90714-2. [DOI] [PubMed] [Google Scholar]
  9. Nelsestuen G. L., Suttie J. W. The mode of action of vitamin K. Isolation of a peptide containing the vitamin K-dependent portion of prothrombin. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3366–3370. doi: 10.1073/pnas.70.12.3366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Price P. A., Otsuka A. A., Poser J. W., Kristaponis J., Raman N. Characterization of a gamma-carboxyglutamic acid-containing protein from bone. Proc Natl Acad Sci U S A. 1976 May;73(5):1447–1451. doi: 10.1073/pnas.73.5.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Seyer J., Glimcher M. J. The amino acid sequence of two O-phosphoserine containing tripeptides isolated from the organic matrix of embryonic bovine enamel. Biochim Biophys Acta. 1969 Jul 1;181(2):410–418. doi: 10.1016/0005-2795(69)90274-8. [DOI] [PubMed] [Google Scholar]
  12. Shapiro A. L., Viñuela E., Maizel J. V., Jr Molecular weight estimation of polypeptide chains by electrophoresis in SDS-polyacrylamide gels. Biochem Biophys Res Commun. 1967 Sep 7;28(5):815–820. doi: 10.1016/0006-291x(67)90391-9. [DOI] [PubMed] [Google Scholar]
  13. Spector A. R., Gray A., Prien E. L., Jr Kidney stone matrix. Differences in acidic protein composition. Invest Urol. 1976 May;13(6):387–389. [PubMed] [Google Scholar]
  14. Stenflo J. A new vitamin K-dependent protein. Purification from bovine plasma and preliminary characterization. J Biol Chem. 1976 Jan 25;251(2):355–363. [PubMed] [Google Scholar]
  15. Stenflo J., Fernlund P., Egan W., Roepstorff P. Vitamin K dependent modifications of glutamic acid residues in prothrombin. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2730–2733. doi: 10.1073/pnas.71.7.2730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Veis A., Spector A. R., Zamoscianyk H. The isolation of an EDTA-soluble phosphoprotein from mineralizing bovine dentin. Biochim Biophys Acta. 1972 Feb 29;257(2):404–413. doi: 10.1016/0005-2795(72)90293-0. [DOI] [PubMed] [Google Scholar]

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