Promotion of thrombin-catalyzed activation of factor XIII by fibrinogen

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Abstract
High-performance liquid chromatography was used to analyze the kinetics of the [human] thrombin-catalyzed release of the activation peptide from the factor XIII zymogen (fibrin-stabilizing factor). The specificity constant (kcat/Km) for this reaction, measured at factor XIII concentrations much below Km, was (0.13-0.16) .times. 106 M-1 s-1 at pH 7.4, .mu. = 0.15, and 37.degree. C. Separate estimates, obtained from the dependence of the initial rates of release of the activation peptide on the concentration of factor XIII, gave values of 10 (.+-. 3) s-1 for kcat and 84 (.+-. 30) .mu.M for Km, in terms of ab protomers of the zymogen. The thrombin-mediated release of the activation peptide was dramatically enhanced in the presence of fibrinogen. The time course of release, in relation to that of fibrinopeptide A, suggested that some des-A-fibrinogen species (e.g., .alpha.2B.beta.2.gamma.2) may be the true activator for promoting the cleavage of the Arg-36 peptide bonds in the a subunits of factor XIII. Generation of factor XIIIa and its substrate (fibrin) apparently is coordinated so that thrombin-mediated zymogen activation proceeds efficiently only after the process of clotting was initiated by the removal of fibrinopeptide A from fibrinogen.