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DOI: 10.1055/s-0038-1644415
SYNERGY OF TRANEXAMIC ACID AND FIBRIN IN THE ENHANCEMENT OF THE ACTIVATION OF GLU-PLASMINOGEN BY UROKINASE
Publication History
Publication Date:
23 August 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/198701/lookinside/thumbnails/10-1055-s-0038-1644415-1.jpg)
The activation rate of Glu-plasminogen (Glu-plg) by urokinase (UK) was enhanced in the presence of either tranexamic acid or fibrin with increase in catalytic rate constant (kcat) without change in Km. The values of kcat increased almost linearly up to 0.5 mM of tranexamic acid concentration and reached a plateau. On the other hand, the presence of increasing concentrations of fibrin resulted in almost hyperbolic increase in kcat values, reaching the plateau level at 0.04 μM. The values of kcat increased three fold at 0.5 mM of tranexamic acid and at 0.04 μM of fibrin. Fibrinogen was less effective and kcat increased two fold in the presence of 1 μM of fibrinogen. Similar kinetic parameters suggest that basic mechanisms underlying the enhanced activation of Glu-plg by UK may be similar between in the presence of tranexamic acid and fibrin. Possibly conformational changes of Glu-plg upon interaction of its lysine binding sites (LBS)< with tranexamic acid or fibrin may be reasons for the enhanced activation. The addition of fibrin to 1 mM tranexamic acid resulted in further increase in kcat of the UK activation of Glu-plg. On the other hand, the addition of tranexamic acid to 0.1 μM of fibrin further increased kcat of the UK activation of Glu-plg. Thus synergy was observed in the activation of Glu-plg by UK between tranexamic acid and fibrin. Fibrin binding site on kringle 5 of Glu-plg may be involved in further increase in the activation rate of Glu-plg by UK in the presence of both fibrin and tranexamic acid in comparison to that in the presence of tranexamic acid alone. Possibly, Glu-plg bound with both tranexamic acid and fibrin (at kringle 5) may be most effectively activated by UK. From the concentrations of fibrin to show 50 % changes of kcat, it is also suggested that two molecules of Glu-plg should bind to one molecule of fibrin monomer.