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8350814 
Journal Article 
Cancer procoagulant (EC 3.4.22.26): The kinetics of its inhibition by e-64 and modulation of the activity by cadmium, copper and tin ions 
Mielicki, WP; Sobolewska, M 
2001 
11 
2 
135-141 
English 
Problem: Cancer procoagulant (CP) is a protease produced by malignant and fetal tissue. The CP activity is inhibited by E-64. However, there is no data on the inhibition kinetics. It is known that Mn2+, Ca2+, Mg2+, Fe2+ and Zn2+ modulate the CP activity. In the present study the kinetics of CP inhibition by E-64 and the influence of other divalent ions: Cd2+, Cu2+ and Sn2+ on the CP activity were evaluated. Methods: CP was isolated from human amnion-chorion. CP activity was determined by 3-stage chromogenic assay and by direct chromogenic assay with the substrate H-D-Ile-Pip-Arg-pNA. Results: The level of CP inhibition by E-64 was dependent on the substrate concentration. However, the maximum velocity (Vmax) of the reaction was not affected by E-64. Both Cu2+ and Sn2+ did not activate CP. In contrast, Cd2+ ions activated the enzyme. Mn2+ ions did not change the activity of Cd2+-activated CP. The activity of Ca2+-activated CP was enhanced by Cd2+ ions. Addition of Mn2+ together with Ca2+ and Cd2+ did not affect the CP activity. Conclusions: E-64 is a competitive inhibitor of CP. Cd2+ ions enhance the activity of CP effecting the protein in a region recognized also by Mn2+ ions. 
Blood coagulation; Cadmium; Cancer procoagulant; Divalent ions