A kinetic model for the alpha-thrombin-catalyzed conversion of plasma levels of fibrinogen to fibrin in the presence of antithrombin III

• Published in: The Journal of biological chemistry Vol. 266; no. 20; pp. 13003 - 13010
• Main Authors: NASKI, M. C, SHAFER, J. A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 15.07.1991
• Subjects: Antithrombin III - pharmacology; Biological and medical sciences; Blood coagulation. Blood cells; fibrin; Fibrin - metabolism; fibrinogen; Fibrinogen - metabolism; Fibrinopeptide B - isolation & purification; Fibrinopeptide B - metabolism; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods, hemostasis, fibrinolysis; Humans; Kinetics; Mathematics; Models, Theoretical; Molecular and cellular biology; Thrombin - metabolism; Human; Blood coagulation; Fibrin; Kinetic model; Fibrinopeptide; Antithrombin III; Enzyme; Fibrinogen; Enzymatic digestion; Enzyme inhibitor; Thrombin; Blood plasma
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)98795-8

In this study we report a kinetic model for the alpha-thrombin-catalyzed production of fibrin I and fibrin II at pH 7.4, 37 degrees C, gamma/2 0.17. The fibrin is produced by the action of human alpha-thrombin on plasma levels of human fibrinogen in the presence of the major inhibitor of alpha-thrombin in plasma, antithrombin III (AT). This model quantitatively accounts for the time dependence of alpha-thrombin-catalyzed release of fibrinopeptides A and B concurrent with the inactivation of alpha-thrombin by AT and delineates the concerted interactions of alpha-thrombin, fibrin(ogen), and AT during the production of a fibrin clot. The model also provides a method for estimating the concentration of alpha-thrombin required to produce a clot of known composition and predicts a direct relationship between the plasma concentration of fibrinogen and the amount of fibrin produced by a bolus of alpha-thrombin. The predicted relationship between the concentration of fibrinogen and the amount of fibrin produced in plasma provides a plausible explanation for the observed linkage between plasma concentrations of fibrinogen and the risk for ischemic heart disease.