Kinetic Analyses of Potentiation of Plasminogen Activation by Streptokinase in the Presence of Fibrin or Its Degradation Products

Abstract

When Glu-plasminogen (Glu-plg) was activated by various amounts of streptokinase (SK), K_m of the hydrolysis of S-2251 by the mixture of Glu-plg and SK did not change, but V_max increased with an increase in the amount of SK. Since low concentrations of SK-plg complex do not result in its conversion to the SK-plasmin complex by mutual activation, these results seem to suggest that the SK-plg complex may be a better activator when S-2251 is used as a substrate. When Glu-plg was activated by SK in the presence of fibrin(ogen) or its degradation products (potentiating agents), K_m did not change with an increase in the concentration of each potentiating agent, but V_max increased. The effects of potentiating agents on the k_cat values of these activators were in the order of fibrin > fibrinogen > D > E.

Enhanced Activator Activity of the Mixture of Streptokinase and a Modified Form of Plasminogen (Lys-Plasminogen) in the Presence of Fibrin: Role of Conformational Change of Plasminogen

“…Km did not change in the presence of such potentiating agents. The results are similar to our previous report showing that the addition of potentiating agents to the mixture of Glu-PLG and SK resulted in increase in kcat without change in Km [5]. Fibrin was most effective in the enhancement of the activator activity (in fact hydrolysis of S-2251) of the mixture of Lys-PLG and SK.…”

“…We have also shown that Glu-PLG changed its conformation upon interaction of its lysine binding sites with fibrin, thereby being activated better by UK [7], Kinetic analyses of the activation of Glu-PLG by UK in the presence of fibrin or other poten tiating agents indicated that kcal of the rate of the conversion of Glu-PLG to plasmin by UK increased in the presence of potentiating agents whereas Km did not change [6], These results are similar to the results of kinetic analyses of the activity of the complex of SK, Glu-PLG and potentiating agents [5], The presence of potentiating agents increased kca, value of the activity of the mixture of SK and Glu-PLG, but Km did not change in their presence. So it seems to be important to know if the enhanced activation of plasmin ogen by SK in the presence of potentiating agents is due to the conformational change of Glu-PLG in their presence.…”

“…Previously we have analyzed kinetically the enhanced activation rate of Glu-PLG by SK in the presence of various potentiating agents and indicated that kcal increased in the presence of potentiating agents whereas Km did not change in their presence [5],…”

“…Kinetic analyses of the activation of a native form of plasminogen (Glu-PLG) by SK indicated that catalytic rate constant (kcal) of the activation of Glu-PLG by SK increased in the presence of fibrin and fi brinogen degradation product, and the effec tiveness was in the order of fibrin, SK poten tiator, fibrinogen, fragment D and fragment E [4,5],…”

Streptokinase - Biochemistry and Clinical Application

“…Studies from several laboratories showed that fibrin, fibrinogen and fragment D en hance the activity of streptokinase [12,[28][29][30][31][32], It was claimed that fibrinogen increases only the rate of formation of an active site in the SK-plasminogen complex and does not have an effect on the activator activity of the SK-plasminogen complex [30]. However, other studies [12,31,32] found that fibrino gen also stimulates the activator activity of the complex.…”