Acceleration of surface-dependent autocatalytic activation of blood coagulation factor XII by divalent metal ions

• Published in: Biochemistry (Easton) 1987-04, Vol.26 (8), p.2250-2258
• Main Authors: Shore, Joseph D, Day, Duane E, Bock, Paul E, Olson, Steven T
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood coagulation. Blood cells; Cations, Divalent; Coagulation factors; Edetic Acid - pharmacology; Enzyme Activation; Factor XII - isolation & purification; Factor XII - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Kinetics; Molecular and cellular biology; Osmolar Concentration; Zinc - pharmacology
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00382a027

The effect of divalent metal ions on the rate of dextran sulfate dependent autocatalytic activation of human blood coagulation factor XII was studied at pH 7.4 and 25 degrees C. Zn2+ and Cu2+, but not Co2+, increased the rate of factor XII activation induced by dextran sulfate with optimum effects at approximately 5 and 1 microM, respectively, while Ca2+ acceleration required much higher concentrations (millimolar). Further investigation of the effect of Zn2+ on factor XII activation demonstrated a complete dependence on the presence of dextran sulfate, lack of inhibition by soybean trypsin inhibitor, the appearance of alpha-XIIa as the primary reaction product, and reaction kinetics characteristic of an autocatalytic process. These results were consistent with Zn2+ affecting only the rate of surface-mediated factor XII autoactivation. The initial turnover velocity of dextran sulfate induced factor XII autoactivation increased linearly with factor XII concentration in the absence of Zn2+ up to 0.9 microM factor XII but showed saturation behavior over this same concentration range in the presence of 5 microM Zn2+, indicating that Zn2+ increased the reaction rate primarily by lowering the apparent Km. Comparison of the kinetics of autoactivation at mu = 0.15 and 0.24 revealed that the enhancement in the apparent kcat/Km brought about by Zn2+ increased from 19-fold to 520-fold, respectively, due to a differential dependence of the Zn2+-stimulated and unstimulated reactions on ionic strength.