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Thromb Haemost 1977; 38(04): 0793-0800
DOI: 10.1055/s-0038-1651898
Original Article
Schattauer GmbH

Degradation Pathway of Fibrinogen by Plasmin

Andrei Z. Budzynski
1   Departments of Medicine and Biochemistry and the Specialized Center of Research in Thrombosis, Temple University Health Sciences Center, Philadelphia, Pennsylvania, 19140, U.S.A.
,
Victor J. Marder   *
1   Departments of Medicine and Biochemistry and the Specialized Center of Research in Thrombosis, Temple University Health Sciences Center, Philadelphia, Pennsylvania, 19140, U.S.A.
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Publication History

Publication Date:
04 July 2018 (online)

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Summary

The molecular weights of derivatives obtained from chemical and enzymatic degradation of fibrinogen and fibrin support a model in which the two halves of the fibrinogen molecule are covalently linked by a set of disulfide bonds at the amino-terminal region. The 2 asymmetric cleavages caused by plasmin in the fibrinogen molecule occur according to the reactions:

X → Y + D

Y → E + D

The quantitative analysis of the amino-terminal amino acids in fragments D (from fibrinogen) and DD (from crosslinked fibrin) yields a total of 3.0 and 6.9 moles of amino acids per mole of protein, indicating three and six polypeptide chain structures, respectively. The data on molecular weights, polypeptide chain composition and immunologic properties of fibrinogen degradation products support the hypothesis on the asymmetric pathway of fibrinogen degradation by plasmin and the formation of two fragment D and one fragment E molecules from each molecule of fibrinogen.

* Present address: Department of Internal Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, N. Y. 14642


 

  • References

  • 1 Alkjaersig N, Fletcher A. P, Sherry S. 1962; Pathogenesis of the coagulation defect developing during pathological plasma proteolytic (»fibrinolytic«) states. II. The significance, mechanism and consequences of defective fibrin polymerization. Journal of Clinical Investigation 41: 917.
    CrossrefPubMedGoogle Scholar
  • 2 Blombäck B, Yamashina I. 1958; On the N-terminal amino acids in fibrinogen and fibrin. Arkiv Kemi 12: 299.
    PubMedGoogle Scholar
  • 3 Blombäck B, Blombäck M, Henschen A, Hessel B, Iwanaga S, Woods K. R. 1968; N-terminal disulfide knot of human fibrinogen. Nature 218: 130.
    CrossrefPubMedGoogle Scholar
  • 4 Blombäck B. 1971; Subunit structure of fibrinogen. Scandinavian Journal of Haematology Suppl. 13: 11.
    PubMedGoogle Scholar
  • 5 Budzynski A. Z, Marder V. J, Shainoff J. R. 1974; Structure of plasmic degradation products of human fibrinogen. Fibrinopeptide and polypeptide chain analysis. Journal of Biological Chemistry 249: 2294.
    PubMedGoogle Scholar
  • 6 Chen R, Doolittle R. F. 1971; γ-γ cross-linking sites in human and bovine fibrin. Biochemistry 10: 4486.
    CrossrefPubMedGoogle Scholar
  • 7 Collen D, Kudryk B, Hessel B, Blombäck B. 1975; Primary structure of human fibrinogen and fibrin. Isolation and partial characterization of chains of Fragment D. Journal of Biological Chemistry 250: 5808.
    PubMedGoogle Scholar
  • 8 Dudek G. A, Kloczewiak M, Budzynski A. Z, Latallo Z. S, Kopec M. 1970; Characterization and comparison of macromolecular end products of fibrinogen and fibrin proteolysis by plasmin. Biochimica et Biophysica Acta 214: 44.
    CrossrefPubMedGoogle Scholar
  • 9 Ferguson E. W, Fretto L. J, McKee P. A. 1975; A re-examination of the cleavage of fibrinogen and fibrin by plasmin. Journal of Biological Chemistry 250: 7210.
    PubMedGoogle Scholar
  • 10 Furlan M, Beck E. A. 1972; Plasmic degradation of human fibrinogen. I. Structural characterization of degradation products. Biochimica et Biophysica Acta 263: 631.
    CrossrefPubMedGoogle Scholar
  • 11 Furlan M, Seelich T, Beck E. A. 1975; Plasmic degradation of human fibrinogen. IV. Identification of subunit chain remnants in Fragment Y. Biochimica et Biophysica Acta 400: 112.
    CrossrefPubMedGoogle Scholar
  • 12 Gaffney P. J, Dobos P. 1971; A structural aspect of human fibrinogen suggested by its plasmin degradation. FEBS letters 15: 13.
    CrossrefPubMedGoogle Scholar
  • 13 Gaffney P. J, Brasher M. 1973; Subunit structure of the plasmin-induced degradation products of crosslinked fibrin. Biochimica et Biophysica Acta 295: 308.
    CrossrefPubMedGoogle Scholar
  • 14 Gaffney P. J. 1973; Subunit relationships between fibrinogen and fibrin degradation products. Thrombosis Research 2: 201.
    CrossrefPubMedGoogle Scholar
  • 15 Hall C. E, Slayter H. S. 1959; The fibrinogen molecule: its size, shape and mode of polymerization. Journal of Biophysiology, Biochemistry, and Cytology 5: 11.
    PubMedGoogle Scholar
  • 16 Henschen A. 1964; S-suIfo-derivatives of fibrinogen and fibrin: Preparations and general properties. Arkiv. Kemi 22: 1.
    PubMedGoogle Scholar
  • 17 Kopec M, Teisseyre E, Dudek-Wojciechowska G, Kloczewiak M, Pankiewicz A, Latallo Z. S. 1973; Studies on the “Double D” fragment from stabilized bovine fibrin. Thrombosis Research 2: 283.
    CrossrefPubMedGoogle Scholar
  • 18 Koppel G. 1966; Electron microscopic investigation of the shape of fibrinogen nodules: A model for certain protein. Nature 212: 1608.
    PubMedGoogle Scholar
  • 19 Kowalska-Loth B, Gardlund B, Egberg N, Blombäck B. 1973; Plasmic degradation products of human fibrinogen. II. Chemical and immunological relation between Fragment E and N-DSK. Thrombosis Research 2: 423.
    CrossrefPubMedGoogle Scholar
  • 20 Marder V. J, Shulman N. R, Carroll W. R. 1967; The importance of intermediate degradation products of fibrinogen in fibrinolytic hemorrhage. Transactions of the Association of American Physicians 53: 156.
    PubMedGoogle Scholar
  • 21 Marder V. J. 1968. Immunologic structure of fibrinogen and its plasmin degradation products. Theoretical and clinical considerations. In: Laki K. (ed.) Fibrinogen. Marcel Dekker, Inc.; New York: 333.
    Google Scholar
  • 22 Marder V. J, James H. L, Sherry S. 1969; a The purification of fibrinogen degradation products by Pevikon block electrophoresis. Thrombosis et Diathesis Haemorrhagica 22: 234.
    PubMedGoogle Scholar
  • 23 Marder V. J, Shulman N. R, Carroll W. R. 1969; b High molecular weight derivatives of human fibrinogen produced by plasmin. I. Physicochemical and immunological characterization. Journal of Biological Chemistry 244: 2111.
    PubMedGoogle Scholar
  • 24 Marder V. J. 1971; Identification and purification of fibrinogen degradation products produced by plasmin. Considerations on the structure of fibrinogen. In: Verstraete M, Vermylen J, Donati M. B. (eds.) Fibrinogen Degradation Products. Int. Workshop, Leuven, Belgium Scandinavian Journal of Haematology Suppl. 13: 21.
    PubMedGoogle Scholar
  • 25 Marder V. J, Budzynski A. Z, James H. L. 1972; High molecular weight derivatives of human fibrinogen produced by plasmin. III. Their NH2-terminal amino acids and comparison with the “NH2 terminal disulfide knot”. Journal of Biological Chemistry 247: 4775.
    PubMedGoogle Scholar
  • 26 Marder V. J, Budzynski A. Z. 1974; Degradation products of fibrinogen and crosslinked fibrin. Projected clinical applications. Thrombosis et Diathesis Haemorrhagica 32: 49.
    PubMedGoogle Scholar
  • 27 Marder V. J, Budzynski A. Z, Barlow G. H. 1976; Comparison of the physicochemical properties of Fragment D derivatives of fibrinogen and Fragment D-D of crosslinked fibrin. Biochimica et Biophysica Acta 427: 1.
    CrossrefPubMedGoogle Scholar
  • 28 Mmalyi E, Weinberg R. M, Towne D. W, Friedman M. E. 1976; Proteolytic fragmentation of fibrinogen. I. Comparison of the fragmentation of human and bovine fibrinogen by trypsin or plasmin. Biochemistry 15: 5372.
    CrossrefPubMedGoogle Scholar
  • 29 Mills D. A. 1972; A molecular model for the proteolysis of human fibrinogen by plasmin. Biochimica et Biophysica Acta 263: 619.
    CrossrefPubMedGoogle Scholar
  • 30 Mills D, Kärpätkin S. 1972; The initial macromolecular derivatives of human fibrinogen produced by plasmin. Biochimica et Biophysica Acta 271: 163.
    CrossrefPubMedGoogle Scholar
  • 31 Mosesson M. W, Finlayson J. S. 1976; The search for the structure of fibrinogen. Progr. Hemost. Thromb 3: 61.
    PubMedGoogle Scholar
  • 32 Mosesson M. W, Finlayson J. S, Galanakis D. K. 1973; The essential covalent structure of human fibrinogen evinced by analysis of derivatives formed during plasmic hydrolysis. Journal of Biological Chemistry 248: 7913.
    PubMedGoogle Scholar
  • 33 Niléhn J. E. 1967; Split products of fibrinogen after prolonged interaction with plasmin. Thrombosis et Diathesis Haemorrhagica 18: 89.
    PubMedGoogle Scholar
  • 34 Nussenzweig V, Seligmann M, Pelmont U, Grabar P. 1961; Le produits de dégradation du fibrinogène humain par la plasmine. I. Séparation et propriétés physicochimiques. Annales de l’Institut Pasteur 100: 377.
    PubMedGoogle Scholar
  • 35 Pizzo S. V, Schwartz M. L, Hill R. L, McKee P. A. 1972; The effect of plasmin on the subunit structure of human fibrinogen. Journal of Biological Chemistry 247: 636.
    PubMedGoogle Scholar
  • 36 Pizzo S. V, Schwartz M. L, Hill R. L, McKee P. A. 1973; a The effect of plasmin on the subunit structure of human fibrin. Journal of Biological Chemistry 248: 4574.
    PubMedGoogle Scholar
  • 37 Pizzo S. V, Taylor Jr. L. M, Schwartz M. L, Hill R. L, McKee P. A. 1973; b Subunit structure of Fragment D from fibrinogen and cross-linked fibrin. Journal of Biological Chemistry 248: 4584.
    PubMedGoogle Scholar
  • 38 Plow E. F, Edgington T. S. 1974; The number of D and E regions in the fibrinogen molecule. Proceedings of the National Academy of Sciences of the United States of America 71: 158.
    CrossrefPubMedGoogle Scholar
  • 39 Takagi T, Doolittle R. F. 1975; Amino acid sequence of the carboxy-terminal cyanogen bromide peptide of the human fibrinogen β-chain: Homology with the corresponding γ-chain peptide and presence in Fragment D. Biochimica et Biophysica Acta 386: 617.
    CrossrefPubMedGoogle Scholar