Differences in the binding to fibrin of native plasminogen and plasminogen modified by proteolytic degradation. Influence of omega-aminocarboxylic acids.
Pretreatment of native plasminogen with plasmin or activators resulted in a pronounced increase in the binding of plasminogen to fibrin. The pretreated plasminogen was considered to be identical to the proteolytically degraded proenzyme with NH2-terminal lysine, valine or methionine, which is formed as an intermediate stage during activation of plasminogen. Bound plasminogen could be extracted by 6-aminohexanoic acid indicating a reversible binding between plasminogen and fibrin. Adsorption of pretreated plasminogen decreased when increasing concentrations of 6-aminohexanoic acid or trans-4-aminomethylcyclohexane-1-carboxylic acid (t-AMCHA) were present during fibrin formation. The concentration of amino acid producing a decrease in the binding of pretreated plasminogen to 0.5 of the amount bound in the absence of amino acid was 8.0-10(-5) M with 6-aminohexanoic acid and 1.7.10-5 M with t-AMCHA. The decrease in binding is most likely related to an effect of the amino acids on plasminogen, since agarose gel electrophoresis of pretreated plasminogen in the presence of 6-aminohexanoic acid or t-AMCHA showed a cathodic shift in mobility at the same range of concentrations of amino acid, which produced the decrease in binding of plasminogen to fibrin. Evidence is provided that the decrease in binding of proteolytically degraded plasminogen may result in an inhibition of fibrinolysis caused by activators.
D000596:Amino Acids; D000818:Animals; D001665:Binding Sites; D001780:Blood Coagulation Tests; D002417:Cattle; D004586:Electrophoresis; D004789:Enzyme Activation; D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin; D006801:Humans; D007700:Kinetics; D010447:Peptide Hydrolases; D010958:Plasminogen / Q000378:metabolism; D011485:Protein Binding; D012685:Sepharose; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator
D000596:Amino Acids; D005337:Fibrin; D010958:Plasminogen; D012685:Sepharose; D010447:Peptide Hydrolases; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator