Factor XI activation in a revised model of blood coagulation.
Coagulation factor XI is activated in vitro by factor XIIa in the presence of high molecular weight kininogen (HMWK) and a negatively charged surface. Factor XII deficiency is not associated with bleeding, which suggests that another mechanism for factor XI activation exists in vivo. A revised model of coagulation is proposed in which factor XI is activated by thrombin. In the absence of cofactors, thrombin is more effective (kcat/Km = 1.6 x 10(5)) than factor XIIa (1.7 x 10(4)) in activating factor XI. Dextran sulfate enhances activation of factor XI by thrombin 2000-fold; part of this effect is due to autoactivation of factor XI by activated factor XI.
Gailani
D
D
Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, MO 63110.
Broze
G J
GJ
D001777:Blood Coagulation; D002863:Chromogenic Compounds / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology; D005172:Factor XI / Q000737:chemistry / Q000378:metabolism*; D015956:Factor XIIa / Q000494:pharmacology; D006487:Hemostasis / Q000502:physiology; D007704:Kininogens / Q000494:pharmacology; D046911:Macromolecular Substances; D008954:Models, Biological; D009842:Oligopeptides / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011956:Receptors, Cell Surface / Q000494:pharmacology; D018179:Receptors, Thrombin; D011994:Recombinant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D002863:Chromogenic Compounds; D007704:Kininogens; D046911:Macromolecular Substances; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D011994:Recombinant Proteins; C040190:S 2366; D005172:Factor XI; D016264:Dextran Sulfate; D015956:Factor XIIa; D013917:Thrombin; D011761:Pyrrolidonecarboxylic Acid