A kinetic model for the alpha-thrombin-catalyzed conversion of plasma levels of fibrinogen to fibrin in the presence of antithrombin III.
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.
Naski
M C
MC
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109.
Shafer
J A
JA
D000990:Antithrombin III / Q000494:pharmacology*; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D005345:Fibrinopeptide B / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008433:Mathematics; D008962:Models, Theoretical; D013917:Thrombin / Q000378:metabolism*
D005345:Fibrinopeptide B; D000990:Antithrombin III; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin