Binding of one-chain tissue-type plasminogen activator to fibrin, partially plasmin-degraded fibrin, lysine and heparin.

Abstract

Tissue-type plasminogen activator (t-PA) binds to heparin with an association constant of 2.4 x 10(4) l/mol at pH 7.4. The binding increases at lower pH-values and reaches maximal values below pH 6.0. Sodium chloride above 0.5 mol/l abolishes t-PA binding to heparin at neutral pH. t-PA binds to lysine maximally at pH 6 to pH 9. At neutral pH the association constant is 1.8 x 10(5) l/mol. Sodium chloride concentrations of 1 mol/l reduce interaction of the enzyme to lysine by about 60% at pH 7.4. Binding of t-PA to fibrin and to partially plasmin-degraded fibrin takes place maximally at pH 6 to 9. The interaction of t-PA with plasmin-degraded fibrin is less sensitive to addition of lysine than the interaction of t-PA and fibrin. Sodium chloride concentrations of 1 mol/l reduce the interaction of t-PA to fibrin by about 60% at pH 7.4.