xi-Aminocaproic acid: an inhibitor of plasminogen activation.

Human and animal sera contain a globulin, plasminogen, which in the presence of activators is rapidly converted to plasmin, a proteolytic enzyme active at neutral hydrogen ion concentrations. Activators specific for plasminogen include streptokinase and staphylokinase of bacterial origin, urokinase and plasma activator found in body fluids, and fibrinokinase derived from tissues. Trypsin, an activator of other enzyme systems, will activate plasminogen, and plasminogen may undergo spontaneous activation. Streptokinase, urokinase, and trypsin activate plasminogen by a first order enzymatic reaction that involves the release of trichloroacetic acid soluble moieties (I), and spontaneous activation involves a similar process (2). Plasmin acts on a number of substrates among which are casein, fibrin, fibrinogen, gelatin, protamine-heparin complex, and certain synthetic substrates containing lysine and arginine esters. Arginine and lysine esters are competitive inhibitors of the proteolytic activity of plasmin (3) as well as of the activator activity of urokinase, streptokinase, and trypsin (1). Numerous inorganic and organic inhibitors of plasmin activity have been described (4, 5) and often the same substances, which include toxic phosphorus compounds (6) also inhibit trypsin. However certain quaternary amines and laurylamine (5, 7), in high concentration, inhibit only plasmin and in low concentration possess the peculiar property of enhancing both the actions of plasmin and trypsin. Hitherto, because of limitations of technical method, infrequent distinction has been made between plasmin inhibitors and inhibitors of plasminogen activation. The present communication describes the effects of e-aminocaproic acid, a newly described “plasmin inhibitor” (8), as an inhibitor of plasminogen activation and also of plasmin. The results indicate that the primary action of e-aminocaproic acid is to inhibit the activation of plasminogen, but that it also possesses, depending upon its concentration, the dual property of either inhibiting or enhancing the action of plasmin.