Sulfatide-dependent autoactivation of human blood coagulation Factor XII (Hageman Factor).
When purified human blood coagulation Factor XII (Hageman factor) is incubated with sulfatides at 37 degrees C, activation of Factor XII occurs as judged by the appearance of amidolytic activity towards the chromogenic substrate H-D-Pro-Phe-Arg-p-nitroanilide. Polyacrylamide gel electrophoresis studies using 125I-Factor XII as a marker show that the appearance of amidolytic activity correlates with Factor XII cleavage, that activation goes to completion and that virtually all Factor XIIa formed is present as the two-chain, 80,000 Mr form, alpha-Factor XIIa. Rigorous analysis of kinetic data establishes that, between 0.02 and greater than 90% of the reaction, the activation of Factor XII is described by a mechanism of autoactivation of Factor XII by Factor XIIa. The rate of autoactivation increases with increasing Factor XII concentrations at constant sulfatide levels but decreases with increasing sulfatide concentrations at constant levels of Factor XII. These findings suggest that the concentrations of Factor XII and Factor XIIa bound to the sulfatide surface determine the rate of autoactivation. Soybean trypsin inhibitor, Trasylol, and anti-prekallikrein antibodies have no influence on the rate of sulfatide-dependent autoactivation of Factor XII. Benzamidine inhibits autoactivation with an inhibitor constant, Ki, of 1.9 mM which is similar to the Ki of 1.5 mM for the enzyme, alpha-Factor XIIa. Thus, sulfatide-dependent activation of purified Factor XII is not due to contaminating proteases and is described by a second order mechanism of autoactivation due to the action of surface-bound Factor XIIa on surface-bound Factor XII.
D001550:Benzamidines / Q000494:pharmacology; D004789:Enzyme Activation; D005174:Factor XII / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007610:Kallikreins / Q000378:metabolism; D007700:Kinetics; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*
D001550:Benzamidines; D013433:Sulfoglycosphingolipids; D005174:Factor XII; D007610:Kallikreins; C032157:benzamidine