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. 1977 Dec;60(6):1410–1418. doi: 10.1172/JCI108902

Generation of the combined prothrombin activation peptide (F1-2) during the clotting of blood and plasma.

D L Aronson, L Stevan, A P Ball, B R Franza Jr, J S Finlayson
PMCID: PMC372499  PMID: 410831

Abstract

We have investigated the pathway of prothrombin activation in blood and plasma. By means of a rapid purification procedure involving chromatography on DEAE-cellulose and hydroxyapatite, we demonstrated that the major prothrombin fragment in serum is that representing the amino-terminal half of prothrombin (i.e. F1-2). The F1-2 isolated was characterized by its size, amino acid and antigenic compositions, amino-terminal residue, and the peptides (designated F1 and F2, respectively) it yielded upon hydrolysis by thrombin. Measurements by the isotope dilution technique showed that F1-2 could account for the fate of at least 90% of the prothrombin originally present in plasma. By contrast, the serum concentration of the fragment representing the amino-terminal third of prothrombin (viz. F1) was less than 10% that of F1-2. These results demonstrated that the major route of prothrombin conversion in blood or plasma involves the removal of the combined activation fragment (F1-2) as a single peptide.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aronson D. L., Ménaché D. Chromatographic analysis of the activation of human prothrombin with human thrombokinase. Biochemistry. 1966 Aug;5(8):2635–2640. doi: 10.1021/bi00872a022. [DOI] [PubMed] [Google Scholar]
  2. DENSON K. W. The specific assay of Prower-Stuart factor and factor VII. Acta Haematol. 1961 Feb;25:105–120. doi: 10.1159/000206523. [DOI] [PubMed] [Google Scholar]
  3. Esmon C. T., Jackson C. M. The conversion of prothrombin to thrombin. III. The factor Xa-catalyzed activation of prothrombin. J Biol Chem. 1974 Dec 25;249(24):7782–7790. [PubMed] [Google Scholar]
  4. Esmon C. T., Owen W. G., Jackson C. M. The conversion of prothrombin to thrombin. II. Differentiation between thrombin- and factor Xa-catalyzed proteolyses. J Biol Chem. 1974 Jan 25;249(2):606–611. [PubMed] [Google Scholar]
  5. Esmon C. T., Owen W. G., Jackson C. M. The conversion of prothrombin to thrombin. V. The activation of prothrombin by factor Xa in the presence of phospholipid. J Biol Chem. 1974 Dec 25;249(24):7798–7807. [PubMed] [Google Scholar]
  6. Fass D. N., Mann K. G. Activation of fluorescein-labeled prothrombin. J Biol Chem. 1973 May 10;248(9):3280–3287. [PubMed] [Google Scholar]
  7. Franza B. R., Jr, Aronson D. L., Finlayson J. S. Activation of human prothrombin by a procoagulant fraction from the venom of Echis carinatus. Identification of a high molecular weight intermediate with thrombin activity. J Biol Chem. 1975 Sep 10;250(17):7057–7068. [PubMed] [Google Scholar]
  8. Ganrot P. O., Niléhn J. E. Prothrombin fragmentation during coagulation of whole blood and plasma. Scand J Clin Lab Invest. 1969 Aug;24(1):15–21. doi: 10.3109/00365516909080126. [DOI] [PubMed] [Google Scholar]
  9. Ganrot P. O., Stenflo J. Prothrombin derivatives in human serum. Isolation and some properties of the non-thrombin fragments. Scand J Clin Lab Invest. 1970 Sep;26(2):161–168. doi: 10.3109/00365517009049229. [DOI] [PubMed] [Google Scholar]
  10. Heldebrant C. M., Butkowski R. J., Bajaj S. P., Mann K. G. The activation of prothrombin. II. Partial reactions, physical and chemical characterization of the intermediates of activation. J Biol Chem. 1973 Oct 25;248(20):7149–7163. [PubMed] [Google Scholar]
  11. Kornalik F., Blombäck B. Prothrombin activation induced by Ecarin - a prothrombin converting enzyme from Echis carinatus venom. Thromb Res. 1975 Jan;6(1):57–63. doi: 10.1016/0049-3848(75)90150-4. [DOI] [PubMed] [Google Scholar]
  12. Lanchantin G. F., Friedmann J. A., Hart D. W. On the occurrence of polymorphic human prothrombin. Electrophoretic and chromatographic alterations of the molecule due to the action of thrombin. J Biol Chem. 1968 Feb 10;243(3):476–486. [PubMed] [Google Scholar]
  13. Morita T., Iwanaga S., Suzuki T. Activation of bovine prothrombin by an activator isolated from Echis carinatus venom. Thromb Res. 1976 May;8(2 Suppl):59–65. doi: 10.1016/0049-3848(76)90048-7. [DOI] [PubMed] [Google Scholar]
  14. Morita T., Iwanaga S., Suzuki T. The mechanism of activation of bovine prothrombin by an activator isolated from Echis carinatus venon and characterization of the new active intermediates. J Biochem. 1976 May;79(5):1089–1108. doi: 10.1093/oxfordjournals.jbchem.a131150. [DOI] [PubMed] [Google Scholar]
  15. Mosesson M. W., Finlayson J. S., Galanakis D. K. The essential covalent structure of human fibrinogen evinced by analysis of derivatives formed during plasmic hydrolysis. J Biol Chem. 1973 Nov 25;248(22):7913–7929. [PubMed] [Google Scholar]
  16. Rosenberg J. S., Beeler D. L., Rosenberg R. D. Activation of human prothrombin by highly purified human factors V and X-a in presence of human antithrombin. J Biol Chem. 1975 Mar 10;250(5):1607–1617. [PubMed] [Google Scholar]
  17. Stenn K. S., Blout E. R. Mechanism of bovine prothrombin activation by an insoluble preparation of bovine factor X a (thrombokinase). Biochemistry. 1972 Nov 21;11(24):4502–4515. doi: 10.1021/bi00774a012. [DOI] [PubMed] [Google Scholar]
  18. Van Lenten L., Ashwell G. Studies on the chemical and enzymatic modification of glycoproteins. A general method for the tritiation of sialic acid-containing glycoproteins. J Biol Chem. 1971 Mar 25;246(6):1889–1894. [PubMed] [Google Scholar]
  19. Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]

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