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Biochemistry of Intra Vascular Clotting: Focus on the Prothrombinase Complex

  • Frederick A. Spencer
  • Richard C. Becker
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 193)

Abstract

The prothrombinase complex plays a pivotal role in the coagulation cascade. It is responsible for the proteolytic conversion of prothrombin to thrombin, which in turn is involved directly in the formation of fibrin, activation of platelets, and feedback activation of other components of the cascade. It is among the most thoroughly studied coagulation processes, and some have suggested that the mechanisms of prothrombinase assembly can serve as a model for understanding other components of the coagulation system. Prothrombinase assembly requires a platelet surface in vivo; thus, this stage of clotting involves a unique interaction between the protein-based coagulation cascade and platelet activity. Accordingly, the investigation and development of antithrombotic compounds has recently been directed toward prothrombinase. In this chapter we summarize the current understanding of prothrombinase assembly and function.

Keywords

Factor Versus Platelet Factor Phospholipid Vesicle Prothrombin Activation Adherent Platelet 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Mann KG. Lawson JH. The role of the membrane in the expression of the vitamin K-dependent enzymes. Arch Pathol Lab Med 116:1330, 1992.PubMedGoogle Scholar
  2. 2.
    Doolirtle RF, Feng DF, Johnson MS. Computer-based characterization of epidermal growth factor precursor. Nature 307:558, 1984.CrossRefGoogle Scholar
  3. 3.
    Mann KG. Nesheim ME, Church WR, Haley P, Krishnaswamy S. Surface-dependent reactions of the vitamin K-dependent enzyme complexes. Blood 76:1, 1990.PubMedGoogle Scholar
  4. 4.
    Church WR, Boulanger LL, Messier TL, Mann KG. Evidence for a common metal ion-dependent transition in the 4-carboxyglutamic acid domains of several vitamin K dependent proteins. J Biol Chem 264:17882, 1989.PubMedGoogle Scholar
  5. 5.
    Malhotra DP, Nesheim ME, Mann KG. The kinetics of activation of normal and gammacarboxyglutamaic acid-deficient prothrombins. J Biol Chem 260:279, 1985.PubMedGoogle Scholar
  6. 6.
    Mann KG, Krishnaswamy S, Lawson JH. Surface dependent hemostasis. Semin Hematol 29:213, 1992.PubMedGoogle Scholar
  7. 7.
    Silverberg SA, Nemerson Y, Zur M. Kinetics of the activation of bovine coagulation factor X by components of the extrinsic pathway. J Biol Chem 252:8481, 1977.PubMedGoogle Scholar
  8. 8.
    Krishnaswamy S, Jones KC, Mann KG. Kinetic mechanism of enzyme assembly on phospholipid vesicles. J Biol Chem 263:3823, 1988.PubMedGoogle Scholar
  9. 9.
    Nesheim ME, Myrmel KH, Hibbard L, Mann KG. Isolation and characterization of single chain bovine factor V. J Biol Chem 254:508, 1979.PubMedGoogle Scholar
  10. 10.
    Viskup RW, Tracy PB, Mann KG. The isolation of human platelet factor V. Blood 69:1188, 1987.PubMedGoogle Scholar
  11. 11.
    Nesheim ME, Nichols WL, Cole TL, Houston JG, Schenk RB, Mann KG, Bovie EJW. Isolation and study of an acquired inhibitor of human coagulation factor V. J Clin Invest 77:405, 1986.PubMedCrossRefGoogle Scholar
  12. 12.
    Rand MD, Kalafatis M, Mann KG. Platelet coagulation factor Va: The major secretory platelet phosphoproteia. Blood 83:2180, 1994.PubMedGoogle Scholar
  13. 13.
    Tracy PB, Giles AR, Mann KG, Elde LL, Hoogendourn H, Riourd GE. J Clin Invest 74:1221, 1984.PubMedGoogle Scholar
  14. 14.
    Bloom JW, Neisheim ME, Mann KG. Phospholipid binding properties of bovine factor V and factor Va. Biochemistry 18:4419, 1979.PubMedCrossRefGoogle Scholar
  15. 15.
    Higgins DL, Mann RG. The interaction of bovine factor V and factor V-derived peptides with phospholipid vesicles. J Biol Chem 258:6503, 1983.PubMedGoogle Scholar
  16. 16.
    Tracy PB, Mann KG. Prothrombinase complex assembly on the platelet surface is mediated through the 74,000 dalton component of factor Va. Proc Natl Acad Sci USA 80:2380, 1983.PubMedCrossRefGoogle Scholar
  17. 17.
    Kalafahs M, Rand MD, Mann KG. Factor Va membrane interaction is mediated by two regions located on the light chain of the cofactor. Biochemistry 33:486, 1994.CrossRefGoogle Scholar
  18. 18.
    Krishnaswamy S, Jones KC, Mann KG. Prothrombinase complex assembly on kinetic mechanism of enzyme assembly on phospholipid vesicles. J Biol Chem 263:3823, 1988.PubMedGoogle Scholar
  19. 19.
    Krishnaswamy S, Field KA, Edgington TS. Morrissey JH, Mann KG. Role of the membrane surface in the activation of human coagulation factor X. J Biol Chem 267:26110, 1992.PubMedGoogle Scholar
  20. 20.
    Pryzdial EL. Mann KG. The association of coagulation factor Xa and factor Va. J Biol Chem 266:8969, 1991.PubMedGoogle Scholar
  21. 21.
    Esmon CT. The subunit structure of thrombin-activated factor V. Isolation of activated factor V, separation of subunits, and reconstitution of biological activity. J Biol Chem 254:964, 1979.PubMedGoogle Scholar
  22. 22.
    Nesheim ME, Mann KG. Thrombin-catalyzed activation of single chain bovine factor V. J Biol Chem 254:1326, 1979.PubMedGoogle Scholar
  23. 23.
    Nesheim ME, Taswell JB, Mann KG. The contribution of bovine factor V and factor Va to the activity of prothrombinase. J Biol Chem 254:10952, 1979.PubMedGoogle Scholar
  24. 24.
    Foster BW, Neisheim ME, Mann KG. The factor Xa catalyzed activation of factor V. J Biol Chem 258:13970, 1983.PubMedGoogle Scholar
  25. 25.
    Monkovic DD, Tracy PB. Activation of human factor V by Xa and thrombin. Biochemistry 29:1118, 1990.PubMedCrossRefGoogle Scholar
  26. 26.
    Krishnaswamy S, Russell GD, Mann KG. The reassociation of factor Va from its isolated subunits. J Biol Chem 264:3160, 1989.PubMedGoogle Scholar
  27. 27.
    Foster WB, Nesheim ME, Mann KG. The factor Xa catalyzed activation of factor V. J Biol Chem 258:13970, 1983.PubMedGoogle Scholar
  28. 28.
    Barron PG, Hanahan DJ. Some lipid protein interactions involved in prothrombin activation. Biochem Biophys Acta 187:319, 1969.Google Scholar
  29. 29.
    Higgins DC, Callahan PJ, Prendergast FG, Newsheim ME, Mann KG. Lipid mobility in the assembly and expression of the activity of the prothrombinase complex. J Biol Chem 260:3604, 1985.PubMedGoogle Scholar
  30. 30.
    Tracy PB, Mann KG. In Wolmsen H (ed). Platelet Responses and Metabolism. Boca Raton, FL: CRC Press, 1986:297.Google Scholar
  31. 31.
    Tracy PB, Nesheim ME, Mann KG. Coordinate binding of factor Va and factor Xa to the unstimulated platelet. J Biol Chem 256:743, 1981.PubMedGoogle Scholar
  32. 32.
    Newrorh PP, Hundley DA, Esmon CT, et al. Interleukin induces endothelial cell procoagulant activity while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci USA 83:3460, 1986.CrossRefGoogle Scholar
  33. 33.
    Nesheim ME, Kettner C, Shaw E, Mann KG. Cofactor dependence of factor Xa incorporation into the prothrombinase complex. J Biol Chem 256:6537, 1979.Google Scholar
  34. 34.
    Nesheim ME, Eid S, Mann KG. Assembly of the prothrombinase complex in the absence ot prothrombin. J Biol Chem 256:9874, 1981.PubMedGoogle Scholar
  35. 35.
    Krishnaswamy S, Church WR, Nesheim ME, Mann KG. Activation of human prothrombin by human prothrombinase. Influence of factor Va on the reaction mechanism. J Biol Chem 262:3291, 1987.PubMedGoogle Scholar
  36. 36.
    Kane WH, Lindhout MJ, Jackson CM, Majerus PW. Factor Va dependent binding of factor Xa to human platelets. J Biol Chem 255:1170, 1980.PubMedGoogle Scholar
  37. 37.
    Miletich JP, Jackson CM, Majerus PW. Properties of the factor Xa binding site on human platelets. J Biol Chem 253:6908, 1978.PubMedGoogle Scholar
  38. 38.
    Miletich JP, Majerus DW, Majerus PW. Patients with congenital factor V deficiency have decreased factor Xa binding sites on their platelets. J Clin Invest 62:824, 1978.PubMedGoogle Scholar
  39. 39.
    Miletich JP, Kane WH, Hoffman SL, Stanford N, Majerus PW. Deficiency of factor Xa-factor Va binding sites on the platelets of a patient with a bleeding disorder. Blood 54:1015, 1979.PubMedGoogle Scholar
  40. 40.
    Kane WH, Lindhout MJ, Jackson CM, Majerus PW. Factor Va-dependent binding of factor-Xa to human platelets. J Biol Chem 255:1170, 1981.Google Scholar
  41. 41.
    Tracy PB, Peterson JM, Nesheim ME, McDuffie FC, Mann KG. Interaction of coagulation factor V and factor Va with platelets. J Biol Chem 254:10354, 1979.PubMedGoogle Scholar
  42. 42.
    Tracy PB, Peterson JM, Nesheim ME, McDuffie FC, Mann KG. In Taylor FB Jr, Mann KG (eds). The Regulation of Coagulation. New York: Elsevier, 1980:237.Google Scholar
  43. 43.
    Mann KG, Nesheim ME, Church WR, Huley P, Krishnaswamy S. Surface-dependent reactions of the vitamin K dependent enzyme complexes. Blood 76:1, 1990.PubMedGoogle Scholar
  44. 44.
    Krishnaswamy S. Prothrombinase complex assembly: Contributions of protein-protein and protein-membrane interactions towards complex formation. J Biol Chem 265:3708, 1990.PubMedGoogle Scholar
  45. 45.
    Krishnaswamy S, Jones KC, Mann KG. Kinetic mechanism of enzyme assembly on phospholipid vesicles. J Biol Chem 263:3823, 1988.PubMedGoogle Scholar
  46. 46.
    Swords NA, Mann KG. The assembly of the prothrombinase complex on adherent platelets. Arterioscleros Thrombos 13:1602, 1993.Google Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Frederick A. Spencer
  • Richard C. Becker

There are no affiliations available

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