The first component of the kinin-forming system in human and rabbit plasma. Its relationship to clotting factor XII (Hageman Factor).
The isolation and characterization of the first component of the kinin-forming system in human and rabbit plasma are presented. Functionally, the molecule is the precursor of the activator of prekallikrein (Pre-PKA) and evidence is presented that it is identical with Hageman factor (clotting factor XII). The component from each plasma possessed similar characteristics. This molecule was found to have a mol wt of 110,000 and sedimentation rate of 4.6S. It migrated in electrophoresis as a beta-globulin, having an isoelectric point of 6.1. Upon activation with glass, kaolin, diatomaceous earth, ellagic acid, or trypsin, the activated molecule converted purified prekallikrein (prokininogenase) to the active enzyme. Clot-promoting activity was associated with the capacity to activate prekallikrein through each procedure of isolation. The clot-promoting factor was in precursor form, requiring treatment with kaolin or trypsin to gain activity. Evidence indicated that the protein was Hageman factor (factor XII): it promoted clotting of factor XII-deficient, but not Factor XI- or IX-deficient plasma, and did not convert fibrinogen to fibrin it bound to and was activated by kaolin or other negatively charged particles in the presence of chelating agents; the activation by kaolin could be prevented by pretreating the kaolin with hexadimethrine bromide (H Br); prekallikrein-activating and clot-promoting activities were identical in their physical properties; and the prekallikrein activator could not be detected in Hageman factor-deficient plasma. Activation of Hageman factor was accompanied by cleavage of the molecule into several fragments, one of which possessed prekallikrein-activating (PKA) and clot-promoting properties. The PKA fragment sedimented at 2.6S and by gel filtration was found to have a molecular weight of 32,000. The PKA possessed only 1/50 the clot-promoting capacity of the freshly activated native molecule.
D000818:Animals; D001609:Beta-Globulins / Q000032:analysis; D001777:Blood Coagulation; D002614:Chelating Agents / Q000494:pharmacology; D002845:Chromatography; D004589:Electrophoresis, Disc; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000302:isolation & purification*; D005174:Factor XII / Q000032:analysis* / Q000502:physiology; D006801:Humans; D007525:Isoelectric Focusing; D007616:Kaolin / Q000494:pharmacology; D007705:Kinins / Q000032:analysis*; D008970:Molecular Weight; D011817:Rabbits; D014357:Trypsin / Q000494:pharmacology; D014461:Ultracentrifugation
D001609:Beta-Globulins; D002614:Chelating Agents; D004792:Enzyme Precursors; D007705:Kinins; D007616:Kaolin; D005174:Factor XII; D014357:Trypsin