Fibrinolysis mediated by tissue plasminogen activator. Disclosure of a kinetic transition

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Abstract
The rate of Glu-plasminogen activation by tissue plasminogen activator was repeatedly determined during a fibrinolytic process. The process was found to proceed via 2 distinct phases. The kinetics of each phase obeyed Michaelis-Menten equation in the first phase; kcat [activation rate] about 0.17 s-1 and Km was about 1 .mu.M. In the 2nd phase, kcat was, 0.13 s-1 and Km was about 0.06 .mu.M. Practically identical results were obtained with 1-chain as with 2-chain tissue plasminogen activator. Transition from 1st to 2nd phase occurred when the system was exposed to a certain degree of plasmin digestion. Electrophoretic analysis demonstrated time correlation between the appearance of minimally degraded fibrin (X-fragments) and the transition. No such correlation was found between transition and conversion of Glu-plasminogen to Lys-plasminogen. The effect can result in an acceleration (up to 13-fold) of the fibrinolytic process once a slight degradation of the fibrin has taken place. In vivo, the effect described may constitute a mechanism that protects a fibrin clot from premature lysis.