Fibrinolysis mediated by tissue plasminogen activator. Disclosure of a kinetic transition.
The rate of 'Glu'-plasminogen activation by tissue plasminogen activator was repeatedly determined during a fibrinolytic process. The process was found to proceed via two distinct phases. The kinetics of each phase obeyed Michaelis-Menten equation: First phase; kcat about 0.17 s-1 and Km about 1 microM, second phase; kcat about 0.13 s-1 and Km about 0.06 microM. Practically identical results were obtained with one-chain as with two-chain tissue plasminogen activator. Transition from first to second phase occurred when the system had been 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.
Norrman
B
B
Wallén
P
P
Rånby
M
M
D000818:Animals; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000096:biosynthesis / Q000378:metabolism; D005342:Fibrinolysis; D007700:Kinetics; D008545:Melanoma; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000502:physiology*
D005337:Fibrin; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin