Inhibition of activated factor XII by antithrombin-heparin cofactor.
The activation of Factor XII occurs via fragmentation of this zymogen into a diverse spectrum of enzymatically potent molecular species. To study the interaction of antithrombin-heparin cofactor and heparin with activated Factor XII, we have employed two forms of this enzyme with widely differing physical characteristics and biologic potencies. Antithrombin-heparin cofactor was found to be a progressive, time-dependent inhibitor of both forms. The addition of heparin dramatically accelerated the rates of these interactions. Furthermore, sodium dodecyl sulfate gel electrophoresis of reduced proteins has indicated that antithrombin-heparin cofactor functions by forming an undissociable complex with either species of the enzyme. This complex represents a 1:1 stoichiometric combination of activated Factor XII and inhibitor. In the presence of heparin, both species undergo virtually instantaneous complex formation with antithrombin-heparin cofactor without exhibiting alterations in dissociability or stoichiometry.
D000510:Alpha-Globulins / Q000494:pharmacology*; D000990:Antithrombin III / Q000494:pharmacology*; D004789:Enzyme Activation; D005174:Factor XII / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007705:Kinins / Q000378:metabolism
D000510:Alpha-Globulins; D007705:Kinins; D000990:Antithrombin III; D005174:Factor XII; D006493:Heparin