Factor XIIa activation of plasminogen is enhanced by contact activating surfaces and Zn2+.
The native form of plasminogen is Glu-plasminogen, which by plasmin cleavage gives Lys-plasminogen. Lys-plasminogen is a considerably better substrate compared with Glu-plasminogen for plasminogenolytic enzymes. The contact activation of the intrinsic pathway of coagulation consisting of factor XII, prekallikrein and high Mr kininogen has been implicated to play a role in the intrinsic fibrinolysis. Here activation of Glu- and Lys-plasminogen by factor XIIa in the absence of prekallikrein/kallikrein and high Mr kininogen was studied in a purified system by the generation of amidolytic activity towards pyroGlu-Phe-Lys-pNA (S-2403), a chromogenic substrate of plasmin. A slow activation rate of both Glu- and Lys-plasminogen by factor XIIa was enhanced approximately 60-fold in the presence of Zn2+ and a negatively charged surface. 6-Aminohexanoic acid further enhanced the activation of Glu-plasminogen but inhibited the activation of Lys-plasminogen. The presence of a specific factor XIIa inhibitor completely prevented the generation of plasmin amidolytic activity indicating that activation was mediated by proteolytical cleavage, although this could not be proven by Western-blotting. Physiological concentration of factor XIIa was as more efficient than soluble u-PA to lyse fibrin as a result of activation of Glu-plasminogen. This did not require the presence of Zn2+ or sulfatide.
Schousboe
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Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Denmark. schousbo@biobase.dk
D015119:Aminocaproic Acid / Q000378:metabolism; D000818:Animals; D002417:Cattle; D004789:Enzyme Activation; D015956:Factor XIIa / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D009842:Oligopeptides / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D013433:Sulfoglycosphingolipids / Q000494:pharmacology; D013499:Surface Properties; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D009842:Oligopeptides; C110926:S 2403; D013433:Sulfoglycosphingolipids; D010958:Plasminogen; D015956:Factor XIIa; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D015032:Zinc; D015119:Aminocaproic Acid