Mechanism of Action of-Amino Acids on Plasminogen Activation and Fibrinolysis Induced by Staphylokinase
Stimulation of Lys-plasminogen (Lys-Pg) and Glu-plasminogen (Glu-Pg) activation under the action of staphyloki-nase and Glu-Pg activation under the action of preformed activator complex plasmin-staphylokinase (Pm-STA) by low concentrations and inhibition by high concentrations of-amino acids (90-140 mM) were found. Maximal stimulation of the activation was observed at concentrations of L-lysine, 6-amino hexanoic acid (6-AHA) and <i>trans-</i>(4-aminomethyl)cyclohexane carboxylic acid 8.0, 2.0, and 0.8 mM, respectively. Sharp decrease in the Lys-Pg activation rate by complex Pm-STA was noted when concentrations of-amino acids were higher than the above mentioned values. It was found that Pm-STA complex formation from a mixture of equimolar concentrations of staphy-lokinase and Glu-Pg or Lys-Pg is stimulated by low concentrations of 6-AHA (to the maximum at 10 mM). Some increase in the activities of plasmin and complex Pm-STA was detected at higher concentrations of 6-AHA (to maxima at 70 and 50 mM, respectively). Inhibitory effects of-amino acids on kinetics of fibrinolysis by staphylokinase, Pm-STA complex and plasmin were compared. It was revealed that inhibition by-amino acids of fibrinolysis by staphylokinase includes blocking the reactions of Pm-STA complex formation, plasminogen activation by this complex, and lysis of fibrin by forming plasmin as a result of displacement of plasminogen and plasmin from fibrin. Thus, the slow stage of Pm-STA complex formation plays an important role in the mechanism of action of-amino acids on Glu-Pg activation and fibrinolysis induced by staphylokinase. Stimulation of Pm-STA complex formation, in addition tochange in Glu-Pg conformation, leads to enhanced Glu-Pg activation rate in the presence of low concentrations of-amino acids. Inhibition by-amino acids of Pm-STA complex formation on fibrin surface is responsible for appearance of long lag phases on curves of fibrinolysis induced by staphylokinase.