Isolation of high molecular weight activators of human plasma prekallikrein.

Two previously undescribed activators of prekallikrein have been purified from human plasma by alcohol frac tionation, ion exchange chromatography, gel filtration, and polyacrylamide gel electrophoresis. Both were apparently homogeneous as judged by electrophoretic mobility and molecular weight. A monomer-dimer relationship between these two activators is suggested by the use of disc gel electrophoresis in sodium dodecyl sulfate under reducing conditions. The monomer termed “large activator” has an estimated molecular weight of 70,000 and migrates as an a-globulin on the polyacrylamide gels. The other activator has an estimated molecular weight of 135,000 and is a P-globulin. No relationship is yet established between these activators and previously described prekallikrein activators, which are of a molecular weight 30,000 to 50,000 and migrate as prealbumin. In contrast to clotting Factor XII (Hageman factor), which also has activator activity, both high molecular weight activators have essentially no clot-promoting activity. Their activator activity is partially inhibited by soybean or lima bean trypsin inhibitors.