Mechanism of action of omega-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 staphylokinase and Glu-Pg activation under the action of preformed plasmin-staphylokinase activator complex (Pm-STA) by low concentrations and inhibition by high concentrations of omega-amino acids (>90-140 mM) were found. Maximal stimulation of the activation was observed at concentrations of L-lysine, 6-aminohexanoic acid (6-AHA), and trans-(4-aminomethyl)cyclohexanecarboxylic acid 8.0, 2.0, and 0.8 mM, respectively. In contrast, the Lys-Pg activation rate by Pm-STA complex sharply decreased when concentrations of omega-amino acids exceeded the above-mentioned values. It was found that formation of Pm-STA complex from a mixture of equimolar concentrations of staphylokinase and Glu-Pg or Lys-Pg is stimulated by low concentrations (maximal at 10 mM) of 6-AHA. Negligible increase in the specific activities of plasmin and Pm-STA complex was detected at higher concentrations of 6-AHA (to maximal at 70 and 50 mM, respectively). Inhibitory effects of omega-amino acids on the rate of fibrinolysis induced by staphylokinase, Pm-STA complex, and plasmin were compared. It was found that inhibition of staphylokinase-induced fibrinolysis by omega-amino acids includes blocking of 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 the fibrin surface. Thus, the slow stage of Pm-STA complex formation plays an important role in the mechanism of action of omega-amino acids on Glu-Pg activation and fibrinolysis induced by staphylokinase. In addition to alpha-->beta change of Glu-Pg conformation, stimulation of Pm-STA complex formation leads to increase in Glu-Pg activation rate in the presence of low concentrations of omega-amino acids. Inhibition of Pm-STA complex formation on fibrin surface by omega-amino acids is responsible for appearance of long lag phases on curves of fibrinolysis induced by staphylokinase.
Levashov
M Yu
MY
Chemical Faculty, Lomonosov Moscow State University, Moscow, 119992, Russia.
Aisina
R B
RB
Gershkovich
K B
KB
Varfolomeyev
S D
SD
D000596:Amino Acids / Q000737:chemistry*; D015119:Aminocaproic Acid / Q000737:chemistry; D004789:Enzyme Activation; D005341:Fibrinolysin / Q000737:chemistry; D005342:Fibrinolysis; D007700:Kinetics; D008666:Metalloendopeptidases / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D010958:Plasminogen / Q000737:chemistry*; D010960:Plasminogen Activators / Q000737:chemistry*
D000596:Amino Acids; D010446:Peptide Fragments; C018998:lysyl-plasminogen; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus; D015119:Aminocaproic Acid