Pathophysiology of Haemostasis and Thrombosis
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Demonstration of a Threshold Response in a Proteolytic Feedback System: Control of the Autoactivation of Factor XIIJesty J.a · Rodriguez J.a, b · Beltrami E.caDivision of Hematology, Department of Medicine, State University of New York, Stony Brook, N.Y., bStrang Laboratory of Cancer Research, Rockefeller University, New York, N.Y., and cDepartment of Applied Mathematics and Statistics, State University of New York, Stony Brook, N.Y., USA
Jolyon Jesty Division of Hematology Health Sciences Center, Stony Brook University Stony Brook, NY 11794-8151 (USA) Tel. +1 631 444 2059, Fax +1 631 444 7530, E-Mail jolyon.jesty@sunysb.edu |
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Pathophysiol Haemos Thromb 2005;34:71–79
Abstract
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 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 contact-activation 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 confirmed.
© 2005 S. Karger AG, Basel
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External Resources
- Jesty J, Beltrami E, Willems G: Mathematical analysis of a proteolytic positive-feedback loop: dependence of lag time and enzyme yields on the initial conditions and kinetic parameters. Biochemistry 1993;32:6266–6274.
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Published online: January 26, 2006
Issue release date: January 2006
Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 0
ISSN: 1424-8832 (Print)
eISSN: 1424-8840 (Online)
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