Skip to main content
  • 17 Accesses

Abstract

One of the most surprising features of living systems is their use of proteases for many physiological functions apart from digestion of food, for when protease function becomes uncontrolled, cell autolysis occurs, with widespread destruction of tissues and later death of the organism. In cells proteases are segregated in special compartments, lysosomes, which offer partial protection for the rest of the cell contents. But the frequency of entry of proteases into the blood stream and their utilisation for a number of protective functions show that compartmentation is not necessary for controlled action of proteases. Control of protease action in the plasma depends on (a) localisation of the site of release of the protease, (b) the control of the amount released and (c) the control of the duration of action of the protease. Here we are only concerned with (c). A major feature controlling the duration of action of proteases in the circulation is reaction with protease inhibitors. The importance of these is well illustrated by the effects of genetic abnormalities which reduce levels or activity of circulating antiproteases. Thus, a low level of alpha-1 proteinase inhibitor is often associated with emphysema, probably from alveolar destruction by white cell elastases1; a low level of Cī inhibitor, with recurrent attacks of angioneurotic oedema2; and a low level of antithrombin III (AT), with recurrent attacks of deep venous thrombosis3,4.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Jeppson, J. O. and Laurell, C. B. (1975). Function and chemical composition of α1 antitrypsin. In Proteases and Biological Control (E. Reich, D. B. Rifkin and E. Shaw, Eds.), Cold Spring Harbor Laboratory, N.Y., p. 405.

    Google Scholar 

  2. Ruddy, S. and Austen, K. F. (1972). Inherited abnormalities of the complement system in man. In The Metabolic Basis of Inherited Disease (J. B. Stanbury, J. B. Wyngaarden and D. S. Frederickson, Eds.), McGraw-Hill, New York, Ch. 71.

    Google Scholar 

  3. Egeberg, O. (1965). Inherited antithrombin deficiency causing thrombophilia. Thromb. Diath. Haemorrh., 13, 516.

    Google Scholar 

  4. Ambruso, D. R., Jacobson, L. J. and Hathaway, W. E. (1980). Inherited antithrombin III deficiency and cerebral thrombosis in a child. Pediatrics, 65, 125.

    Google Scholar 

  5. Abildgaard, U. (1982). Antithrombin and related inhibitors of coagulation. In Recent Advances in Blood Coagulation, Churchill Livingstone, London.

    Google Scholar 

  6. Barrowcliffe, M. A., Johnson, E. A. and Thomas, D. (1978). Antithrombin III and heparin. Br. Med. Bull., 34, 143.

    Google Scholar 

  7. Rosenberg, R. D. (1977). Chemistry of the hemostatic mechanism and its relationship to the action of heparin. Fed. Proc., 36, 10.

    Google Scholar 

  8. Rosenberg, R. D. and Damus, P. S. (1973). The purification and mechanism of action of human antithrombin-heparin cofactor. J. Biol. Chem., 248, 6490.

    Google Scholar 

  9. Miller-Andersson, M., Borg, H. and Andersson, L. O. (1974). Purification of antithrombin III by affinity chromatography. Thromb. Res., 5, 439.

    Article  Google Scholar 

  10. Reeve, E. B., Leonard, B. and Carlson, T. (1981). Kinetic studies in vivo of antithrombin III. Ann. N.Y. Acad. Sci., 370, 680.

    Article  Google Scholar 

  11. Reeve, E. B., Leonard, B., Wentland, S. H. and Damus, P. (1980). Studies with 133I-labelled antithrombin in dogs. Thromb. Res., 20, 375.

    Article  Google Scholar 

  12. Jesty, J. (1979). Dissociation of complexes and their derivatives formed during inhibition of bovine thrombin and activated factor X by antithrombin III. J. Biol. Chem., 254, 1044.

    Google Scholar 

  13. Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, Lond., 227, 680.

    Article  Google Scholar 

  14. Weber, K. and Osborn, M. (1969). The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J. Biol. Chem., 244, 4406.

    Google Scholar 

  15. Damus, P. S. and Rosenberg, R. D. (1976). Antithrombin-heparin cofactor. In Methods in Enzymology XLV: Proteolytic Enzymes B (L. Lorand, Ed.), Academic Press, New York, p. 653.

    Chapter  Google Scholar 

  16. Bradshaw, R. A. and Wessler, S. (1974). Heparin, Plenum Press, New York.

    Google Scholar 

  17. Lam, L. H., Silbert, J. E. and Rosenberg, R. D. (1977). The separation of active and inactive forms of heparin. Biochem. Biophys. Res. Commun., 69, 570.

    Article  Google Scholar 

  18. Hook, M., Bjork, I., Hopwood, J. and Lindahl, U. (1976). Anticoagulant activity of heparin: separation of high-activity and low-activity heparin species by affinity chromatography on immobilized antithrombin. FEBS Lett., 66, 90.

    Article  Google Scholar 

  19. Jordan, R., Beeler, D. and Rosenberg, R. (1979). Fractionation of low molecular weight heparin species and their interaction with antithrombin. J. Biol. Chem., 254, 2902.

    Google Scholar 

  20. Carlson, T. H. and Atencio, A. C. (1982). Isolation and partial characterization of two distinct types of antithrombin III from rabbit. Thromb. Res., 27, 23.

    Article  Google Scholar 

  21. Tollefsen, T. M., Majerus, D. W. and Blank, M. K. (1982). Heparin cofactor II. J. Biol. Chem., 257, 2162.

    Google Scholar 

  22. Abildgaard, U. (1967). Purification of two progressive antithrombins of human plasma. Scand. J. Clin. Lab. Invest., 19, 190.

    Article  Google Scholar 

  23. Fish, W. W., Orre, K. and Bjork, I. (1979). Routes of thrombin action in the production of proteolytically modified secondary forms of antithrombin-thrombin complex. Eur. J. Biochem., 101, 39.

    Article  Google Scholar 

  24. Bjork, I., Jackson, C. M., Jornvall, H., et al. (1982). The active site of antithrombin. J. Biol. Chem., 257, 2406.

    Google Scholar 

  25. Lundblad, R. L., Kingdon, H. S. and Mann, K. G. (1967). Thrombin. In Methods in Enzymology XLV: Proteolytic Enzymes B (L. Lorand, Ed.), Academic Press, New York, p. 156.

    Google Scholar 

  26. Witt, I. (1977). New Methods for the Analysis of Coagulation Using Chromogenic Substrates, de Gruyter, Berlin.

    Google Scholar 

  27. Gaffney, P. J., Lord, K., Brasher, M. and Kirkwood, T. B. L. (1977). Problems in the assay of thrombin using synthetic peptides as substrates. Thromb. Res., 10, 549.

    Article  Google Scholar 

  28. Machovich, R., Sorbodi, A., Blasko, G. and Orakzai, S. A. (1977). Inactivation of α- and β-thrombin by antithrombin III, α 2-macroglobulin and α 1-proteinase inhibitor. Biochem. J., 167, 393.

    Article  Google Scholar 

  29. Chang, T., Feinman, R. D., Landis, B. H. and Fenton, J. W. (1979). Antithrombin reactions with α- and γ-thrombins. Biochemistry, 18, 113.

    Article  Google Scholar 

  30. Odegard, O. R., Abildgaard, U., Lie, M. and Miller-Andersson, M. (1977). Inactivation of bovine and human thrombin and factor Xa by antithrombin III studied with amidolytic methods. Thromb. Res., 11, 205.

    Article  Google Scholar 

  31. Abildgaard, U. (1968). Inhibition of the thrombin fibrinogen reaction by heparin in the absence of cofactor. Scand. J. Haematol., 5, 432.

    Article  Google Scholar 

  32. Nordenman, B. and Bjork, I. (1981). Influence of ionic strength and pH on the interaction between high affinity heparin and antithrombin. Biochim. Biophys. Acta, 672, 227.

    Article  Google Scholar 

  33. Carlstrom, A.-S., Lieden, K. and Bjork, I. (1977). Decreased binding of heparin to antithrombin following the interaction between antithrombin and thrombin. Thromb. Res., 11, 785.

    Article  Google Scholar 

  34. McKay, E. J. and Laurell, C. B. (1980). The interaction of heparin with plasma proteins. J. Lab. Clin. Med., 95, 69.

    Google Scholar 

  35. Marciniak, E. (1981). Thrombin-induced proteolysis of human antithrombin III: an outstanding contribution of heparin. Br. J. Haematol., 48, 325.

    Article  Google Scholar 

  36. Jacobsson, K.-G. and Lindahl, U. (1979). Attempted determination of endogenous heparin in blood. Thromb. Haemost., 42, 84 (Abstract).

    Google Scholar 

  37. Thomas, D. P., Merton, R. E., Barrowcliffe, T. W., Mulloy, B. and Johnson, E. A. (1979). Antifactor Xa activity of heparan sulphate. Thromb. Res., 14, 507.

    Article  Google Scholar 

  38. Dawes, J. and Pepper, D. S. (1982). A sensitive competitive binding assay for exogenous and endogenous heparins. Thromb. Res., 27, 387.

    Article  Google Scholar 

  39. Kurachi, K., Fujikawa, K., Schmer, G. and Davie, E. W. (1976). Inhibition of bovine factor IXa and factor Xaβ by antithrombin III. Biochemistry, 15, 373.

    Article  Google Scholar 

  40. Yin, E. T., Wessler, S. and Stoll, P. J. (1971). Biological properties of the naturally occurring plasma inhibitor to activated factor X. J. Biol. Chem., 246, 3703.

    Google Scholar 

  41. Osterud, B., Miller-Andersson, M., Abildgaard, U. and Prydz, H. (1976). The effect of antithrombin III on the activity of the coagulation factors VII, IX and X. Thromb. Haemost., 35, 295.

    Google Scholar 

  42. Rosenberg, R. D. (1978). Heparin, antithrombin and abnormal clotting. Ann. Rev. Med., 29, 367.

    Article  Google Scholar 

  43. Burrowes, C. E., Habal, F. M. and Movat, H. Z. (1975). The inhibition of human plasma kallikrein by antithrombin III. Thromb. Res., 7, 175.

    Article  Google Scholar 

  44. Lorand, L. (Ed.) (1975).Methods in Enzymology, Vol. 45, Academic Press, New York.

    Google Scholar 

  45. Lorand, L. (Ed.) (1981). Methods in Enzymology, Vol. 80, Academic Press, New York.

    Google Scholar 

  46. Jesty, J. (1978). The inhibition of activated bovine coagulation factors X and VII by antithrombin III. Arch. Biochem. Biophys., 185, 165.

    Article  Google Scholar 

  47. Kobayashi, N. and Takeda, Y. (1977). Studies of the effects of estradiol, progesterone, cortisol, thrombophlebitis and typhoid vaccine on synthesis and catabolism of antithrombin III in the dog. Thromb. Haemost., 37, 111.

    Google Scholar 

  48. Collen, D., Schetz, J., de Cock, F., Holmer, E. and Verstraete, M. (1977). Metabolism of antithrombin III (heparin cofactor) in man: effects of venous thrombosis and of heparin administration. Eur. J. Clin. Invest., 7, 27.

    Article  Google Scholar 

  49. Vogel, C. N., Kingdon, H. S. and Lundblad, R. L. (1977). In vivo characterization of rabbit thrombin, antithrombin III and thrombin-antithrombin III complex and determination of their survival times in vivo. Thromb. Haemost., 38, 119.

    Google Scholar 

  50. Chan, V., Lai, C. L. and Chan, T. K. (1981). Metabolism of antithrombin III in cirrhosis and carcinoma of the liver. Clin. Sci., 60, 681.

    Article  Google Scholar 

  51. Reeve, E. B. and Chen, Y.-H. (1982). Models of plasma protein turnover in steady and non-steady states. In Quantitative Approaches to Metabolism (D. G. Cramp, Ed.), Wiley, New York, p. 329.

    Google Scholar 

  52. Takeda, Y. and Reeve, E. B. (1962). Distribution and excretion of I131-iodide in men on pharmacologic doses of iodides. J. Lab. Clin. Med., 60, 944.

    Google Scholar 

  53. Reeve, E. B., Bies, R. D. and Leonard, B. (1983). In preparation.

    Google Scholar 

  54. Ambruso, D. R., Leonard, B. D., Bies, R. D., Jacobson, L., Hathaway, W. E. and Reeve, E. B. (1982). Antithrombin III deficiency: decreased synthesis of a biochemically normal molecule. Blood, 60, 78.

    Google Scholar 

  55. Sas, G., Blasko, G., Banhegyi, D., Jako, J. and Palos, L. A. (1974). Abnormal antithrombin III (antithrombin III ‘Budapest’) as a cause of a familial thrombophilia. Thromb. Diath. Haemorrh., 32, 105.

    Google Scholar 

  56. Fagerhol, M. D. and Abildgaard, U. (1970). Immunological studies on human antithrombin III. Influence of age, sex and use of oral contraceptives on serum concentration. Scand. J. Haematol., 7, 10.

    Article  Google Scholar 

  57. Gordon, E. M., Ratnoff, O. D. and Jones, P. K. (1982). Role of augmented Hageman factor titers in cold promoted activation of factor VII and spontaneous shortening of prothrombin time in women using oral contraceptives. J. Lab. Clin. Med., 99, 363.

    Google Scholar 

  58. Kahle, L. H., Schipper, H. G., Jenkins, C. S. P. and ten Cate, J. W. (1978). Antithrombin III: evaluation of an automated antithrombin III method. Thromb. Res., 12, 1003.

    Article  Google Scholar 

  59. Odegard, O. R. and Abildgaard, U. (1978). Antithrombin III: critical review of assay methods. Haemostasis, 7, 127.

    Google Scholar 

  60. Reeve, E. B. (1980). Steady state relations between factors X, Xa, II, IIa, antithrombin III and alpha-2 macroglobulin in thrombosis. Thromb. Res., 18, 19.

    Article  Google Scholar 

  61. Koj, A. and Regoeczi, E. (1978). Effect of experimental inflammation on the synthesis and distribution of antithrombin III and al-antitrypsin in rabbits. Br. J. Exp. Pathol., 59, 473.

    Google Scholar 

  62. Leonard, B., Bies, R., Carlson, T. and Reeve, E. B. (1983). Further studies of the turnover of dog antithrombin III. Thromb. Res., 30, 165.

    Article  Google Scholar 

  63. Fischer, A. M., Bros, A., Rafowicz, S. and Josso, F. (1979). Inhibition par l’heparine de l’activité antithrombique de l’α 2 macroglobuline. C. R. Acad. Sci., Paris, 288, 887.

    Google Scholar 

  64. Fischer, A. M., Tapon-Bretandiere, J., Bros, A. and Josso, F. (1981). Respective roles of antithrombin III and alpha 2 macroglobulin in thrombin inactivation. Thromb. Haemost., 45, 51.

    Google Scholar 

  65. Koj, A., Regoeczi, E., Toews, C. J., Leveille, R. and Gauldce, J. (1978). Synthesis of antithrombin III and alpha-1-antitrypsin in the perfused rat liver. Biochim. Biophys. Acta, 539, 496.

    Article  Google Scholar 

  66. Chan, T. K. and Chan, V. (1981). Antithrombin III, the major modulator of intravascular coagulation, is synthesized by human endothelial cells. Thromb. Haemost., 46, 504.

    Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Copyright information

© 1984 The contributors

About this chapter

Cite this chapter

Reeve, E.B., Bies, R.D., Leonard, B.D., Stephens, A. (1984). Studies of antithrombin turnover. In: Mariani, G. (eds) Pathophysiology of Plasma Protein Metabolism. Palgrave, London. https://doi.org/10.1007/978-1-349-06680-3_14

Download citation

Publish with us

Policies and ethics