On the formation of different types of plasmin by streptokinase activation.

Plasminogen, a normal constituent of human blood plasma, can be activated in various ways to yield the proteolytic enzyme plasmin capable of dissolving fibrin clots and of hydrolyzing a variety of other proteins and synthetic amino acid esters. The activation by the bacterial product streptokinase has been widely studied in the past and appears to proceed through a two-stage reaction: the interaction of streptokinase with plasminogen (1) (or a hypothetical substance called proactivator) (2) yielding “activator,” which in turn converts plasminogen to plasmin. The conversion of plasminogen to plasmin by streptokinase has been reported to result in a decrease in molecular weight from 143,000 to 120,000 (3). The fibrinolytic and caseinolytic activities of streptokinase-activated plasminogen have been invariably attributed to the end product of this reaction. The studies reported here were designed to test the functional homogeneity of the product resulting from the addition of streptokinase to human plasminogen. The possibility that more than one enzyme is produced by streptokinase activation was suggested by our earlier studies (reported in abstracts, 4-6) which indicated that maximal fibrinolytic activities develop within one minute after the addition of streptokinase, before measurable amounts of peptides are released. This finding suggested that at least part of the hydrolytic activity of plasmin may be attributed to a molecular species which appears earlier in the course of activation than the one characterized by the loss of a peptide moiety. The existence of several active components was demonstrated by the measurement of the rates at which activities toward different substrates develop and by the use of inhibitors. Experiments with physical separation methods are in progress.