Demonstration of a Threshold Response in a Proteolytic Feedback System: Control of the Autoactivation of Factor XII

Jolyon Jesty, José Rodriguez, Edward Beltrami
2005 Pathophysiology of Haemostasis and Thrombosis  
Mathematical analysis of positive feedback loops in proteolytic systems has previously suggested that when the active enzymes are subject to inhibitory control these systems will exhibit threshold behavior. This is demonstrated in the present study, for the autolytic activation of factor XII in the presence of a contact activator and an irreversible inhibitor of factor XIIa. The threshold between the two system states -complete factor XII activation, or complete stability -is dependent on the
more » ... dependent on the kinetic balance between the catalytic rate of autoactivation and rate of enzyme (factor XIIa) inhibition. Activation of the system can be brought about by either increasing the catalytic rate (in this study, by using more potent contactactivation conditions), or by lowering the enzyme inhibition rate. Previous mathematical work predicted complete stability in a positive-feedback system that is below threshold, and this has been experimentally confi rmed.
doi:10.1159/000089928 pmid:16432309 fatcat:p332ehmxwvcjlk3xkfw67dgahy