title: Factor XIIa is a kinetically favorable plasminogen activator.
abstract: Initiation of the plasma contact system has been shown to play a significant role in the fibrinolysis, activating both pro-urokinase and plasminogen. The aim of the present study was to further evaluate the functional role of the factor XIIa catalyzed activation of plasminogen. Activation of plasminogen by factor XIIa followed the Michaelis-Menten rate equation. In a continuous assay system the Km was 0.27 microM; the kcat 0.078 min(-1) and the kcat/Km 0.31x10(6) M(-1) x min(-1). In an end-point assay system the Km was 0.58 microM; the kcat 0.096 min(-1) and the kcat/Km 0.16x10(6) M(-1) x min(-1). The discrepancy between the kcat in the two assays is not significant. Theoretically the higher Km in the end-point assay system may be due to the presence or generation of an unidentified competitive inhibitor in this assay system. Comparing the catalytic constants of factor XIIa with those of urokinase activation of plasminogen, the specificity constant, kcat/Km, of factor XIIa activation of plasminogen was 20-fold lower. However, taking the low physiological concentration of urokinase into account, the efficiency of activated factor XII is equivalent to that of urokinase. When monitoring factor XIIa activation of plasminogen in a clot lysis assay, the clot lysis time was 2- to 4-fold as long as that accommodated by urokinase at factor XIIa concentrations equivalent with 5-20% of the zymogen concentration in plasma. The factor XIIa mediated clot lysis was prevented completely by the presence of a polyclonal antibody to factor XII.
authors.affiliation: Department of Medical Biochemistry & Genetics, The Panum Institute, University of Copenhagen, Denmark.
authors.forename: I
authors.initials: I
authors.lastname: Schousboe
authors.forename: K
authors.initials: K
authors.lastname: Feddersen
authors.forename: R
authors.initials: R
authors.lastname: Røjkjaer
mesh_terms: D000818:Animals; D002417:Cattle; D015956:Factor XIIa / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D010958:Plasminogen; D010960:Plasminogen Activators; D015956:Factor XIIa; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator