Prothrombin Activation by Platelet-associated Prothrombinase Proceeds through the Prethrombin-2 Pathway via a Concerted Mechanism

摘要: The protease α-thrombin is a key enzyme of the coagulation process as it at cross-roads both pro- and anti-coagulant pathways. main source in vivo activation prothrombin by prothrombinase complex assembled on either an activated cell membrane or fragment, most relevant which platelet surface. When synthetic phospholipid vesicles, proceeds with initial cleavage Arg-320 yielding catalytically active, yet effectively anticoagulant intermediate meizothrombin, released from ∼30–40% time. Prothrombinase surface platelets has been shown to proceed through inactive prethrombin-2 via Arg-271 followed Arg-320. current work tests whether not platelet-associated concerted mechanism study assembly function collagen-adhered, thrombin-activated, washed human flow chamber. was demonstrated visualization bound factor Xa confocal microscopy using fluorophore-labeled anti-factor antibody, presence distinct subpopulations capable binding Xa. monitored typical venous shear rate over preassembled neither potential intermediate, meizothrombin prethrombin-2, observed effluent. Collectively, these findings suggest that activates efficient released.