Inactivation of α- and β-Thrombin by Antithrombin-III and Heparin

Raymund Machovich; György Blaskó; Anna Borsodi

doi:10.1055/s-0038-1648069

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1976; 36(03): 503-508
DOI: 10.1055/s-0038-1648069

Original Article

Schattauer GmbH

Inactivation of α- and β-Thrombin by Antithrombin-III and Heparin

Raymund Machovich

¹Postgraduate Medical School, First Department of Medicine, 1389 Budapest

²Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, 6701 Szeged, Hungary

,

György Blaskó

¹Postgraduate Medical School, First Department of Medicine, 1389 Budapest

²Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, 6701 Szeged, Hungary

,

Anna Borsodi

¹Postgraduate Medical School, First Department of Medicine, 1389 Budapest

²Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, 6701 Szeged, Hungary

› Author Affiliations

Abstract

Summary

Inactivation of α- and β-thrombin by antithrombin-III and heparin was studied, since it had been suggested that two forms of thrombin exist with respect to heparin sensitivity (Machovich 1975b).

It was found that the inactivation rates of α- and β-thrombin by antithrombin were different, namely α-thrombin was more sensitive to antithrombin than β-thrombin. Heparin facilitated the complex formation between α-thrombin and antithrombin-III, whereas β-thrombin inactivation was only slightly affected.

Furthermore, heparin protected α-thrombin against the inactivating effect of heat, while β-thrombin lost its activity during the heat treatment.

These findings suggest that the formation of β-thrombin in blood circulation may have an important role in thrombosis predisposition.

Full Text

References

References
1 Borsodi A, Bradshaw A. R. 1976 Purification of human antithrombin-III. Thrombosis Research. in press.
2 Damus P. S, Hicks M, Rosenberg R. 1973; Anticoagulant action of heparin. Nature 246: 355.
3 Glover G, Shaw E. 1971; The purification of thrombin and isolation of a peptide containing the active center histidine. Journal of Biological Chemistry 246: 4594.
4 Gorman J. J, Castaldi P. A. 1974; Isolation and characterisation of multiple forms of human thrombin. Thrombosis Research 4: 653.
5 Lanchantin G. F, Friedmann J. A, Hart D. W. 1973; Two forms of human thrombin. Isolation and characterisation. Journal of Biological Chemistry 248: 5956.
6 Li E. H. H, Orton Ch, Feinman R. D. 1974; The interaction of thrombin and heparin. Proflavine dye binding studies. Biochemistry 13: 5012.
7 Lowry O. H, Rosebrough N, Farr A. L, Randall R. J. 1951; Protein measurement with Folin phenol reagent. Journal of Biological Chemistry 193: 265.
8 Lundblad R. L. 1971; A rapid method for the purification of bovine thrombin. Biochemistry 10: 2501.
9 Lundblad R. L, Uhteg L. C, Vogel C. N, Kingdon H. S, Mann K. G. 1975; Preparation and partial characterisation of two forms of bovine thrombin. Biochemical and Biophysical Research Communications 66: 482.
10 Machovich R. 1975; a Mechanism of action of heparin through thrombin on blood coagulation. Biochimica et Biophysica Acta 412: 13.
11 Machovich R. 1975; b Heparin sensitive and nonsensitive forms of thrombin. Biochimica et Biophysica Acta 400: 62.
12 Machovich R. 1975; c Heparin levels and blood coagulation. Thrombosis et Diathesis Haemorrhagica 34: 867.
13 Machovich R, Blaskó Gy, Pálos Á. L. 1975; a Action of heparin on thrombin-antithrombin reaction. Biochimica et Biophysica Acta 379: 193.
14 Machovich R, Blaskó Gy, Arányi P. 1975; b The interaction of thrombin and heparin. Heat inactivation kinetics. Thrombosis Research 7: 253.
15 Mann K. G, Batt C. W. 1969; The molecular weight of bovine thrombin and its primary autolysis products. Journal of Biological Chemistry 244: 6555.
16 Mann K. G, Yip R, Heldebrandt Ch. M, Fass D. N. 1973; Multiple active forms of thrombin. Journal of Biological Chemistry 248: 1868.
17 Pálos Á. L. 1949; Protecting effect of heparin on the inactivation of thrombin by heat. Proceedings of the Society for Experimental Biology and Medicine 71: 471.
18 Seegers W. H, Walz D. A, Reuterby J, McCoy L. E. 1974; Isolation and some properties of thrombin-E and other prothrombin derivatives. Thrombosis Research 4: 829.