Enhancement of the activation of Glu-plasminogen by urokinase in the simultaneous presence of tranexamic acid or fibrin.
The activation rate of Glu-plasminogen (Glu-plg) by urokinase (UK) was enhanced in the presence of either tranexamic acid or fibrin with an increase in the catalytic rate constant (kcat). The maximum increase in kcat was obtained at 0.5 mM of tranexamic acid and 0.1 microM of fibrin. Km did not change. The addition of fibrin to 1 mM tranexamic acid resulted in a further increase in kcat of the UK activation of Glu-plg. On the other hand, the addition of tranexamic acid to 0.1 microM fibrin further increased kcat of the UK activation of Glu-plg. Thus, stimulatory effects were observed on the activation of Glu-plg by UK in the simultaneous presence of tranexamic acid and fibrin. Fibrin-binding sites on the kringle 5 of Glu-plg may be involved in the 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, the Glu-plg binding with both tranexamic acid and fibrin (at kringle 5) may be most effectively activated by UK. It is also suggested that two molecules of Glu-plg bind to one molecule of fibrin monomer.
Takada
A
A
Department of Physiology, Hamamatsu University, School of Medicine, Shizuoka-ken, Japan.
Sugawara
Y
Y
Takada
Y
Y
D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005337:Fibrin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D014148:Tranexamic Acid / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*
D003509:Cyclohexanecarboxylic Acids; D014148:Tranexamic Acid; D005337:Fibrin; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator