Studies on the kinetics of plasminogen activation by tissue plasminogen activator.
The steady-state rate of plasminogen activation by tissue plasminogen activator has been determined at various plasminogen concentrations. A plasmin substrate method similar to that presented by Christensen and Müllertz (Biochim. Biophys. Acta 480 (1977) 257-281) was used. The reaction was studied using one-chain type and two-chain type tissue plasminogen activator, N-terminal glutamic acid and N-terminal lysine plasminogen in the presence and in the absence of fibrin (eight studies). The kinetic data were fitted to a general Wong-Hanes equation and the simplest equation with significant parameters was found. In the absence of fibrin N-terminal glutamic acid plasminogen activation obeyed the Michaelis-Menten rate equation (Km 4.9 and 7.6 micro M and kcat 0.0013 and 0.0078 s-1 for one-chain type and two-chain type tissue plasminogen activator, respectively. In the absence of fibrin the activation of N-terminal lysine plasminogen activation failed to obey the Michaelis-Menten rate equation. Fibrin was found to stimulate greatly (up to 1000-fold) the steady-state activation rate. A theory for the fibrin stimulating mechanism is presented.
D000818:Animals; D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008433:Mathematics; D010446:Peptide Fragments / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism*; D013552:Swine
D010446:Peptide Fragments; C018998:lysyl-plasminogen; D005337:Fibrin; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin