Abstract
Steady state kinetic studies have provided evidence for intrinsic prothrombinase activity of human factor X zymogen in a chromogenic assay system. Using a prothrombin substrate, kinetic parameters have been obtained for the action of factors X and Xa. The K m for prothrombin is of a different order of magnitude for the zymogen as compared with the active enzyme. Using a kinetic approach, we have obtained evidence for the binding of factor X zymogen to cofactors essential for the coagulant activity of factor Xa. Zymogen enzymatic activity is not inhibited by a specific serine proteinase inhibitor, (p-amidino-phenyl)methanesulfonyl flouride (p-APMSF), a potent inhibitor of factor Xa. The apparent slow rate of zymogen inhibition by antithrombin III (AT III) as compared with the active enzyme suggests a different kind of zymogen-antithrombin interaction. Blood clotting studies paralleled the kinetic data. Factor X zymogen evidences factor VIII inhibitor bypassing activity (FEIBA) in an in vitro direct clotting system employing factor VIII deficient inhibitor plasma as substrate in both activated or nonactivated partial thromboplastin assay. Most significantly, zymogen coagulant is refractory to inhibition by p-APMSF or AT III. We conclude that a system consisting of factor X zymogen-phospholipid-factor Va can physiologically initiate blood clotting in the presence of inhibitors and may have a major role in the bypass mechanism of therapeutic prothrombin complex concentrate (PCC).
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.