The function of the heavy and light chain of human plasma kallikrein in the activation of factor XII.
In this paper we report the effect of sulfatides on rate constants of Factor XII activation by kallikrein and its isolated light chain. In free solution kallikrein and the light chain were equally effective in activating Factor XII and both enzymes had their pH optimum at pH 7.0 (k1 = 1.6 X 10(3) M-1 s-1). Sulfatides greatly stimulate Factor XII activation. When sulfatides were present kallikrein was, however, much more effective than its light chain. At 330 microM sulfatides and pH 7.0 the rate constants of Factor XII activation were 5.3 X 10(6) M-1 s-1 and 4.2 X 10(4) M-1 s-1 for kallikrein and its light chain, respectively. In the presence of sulfatides, Factor XII activation by kallikrein had its pH optimum at 6.3 and the rate constant increased considerably at lower ionic strength. Light chain-dependent Factor XII activation in the presence of sulfatides, was optimal at pH 7.0 and was not affected by variation of the ionic strength. Binding studies revealed that kallikrein, Factor XII and the heavy chain of kallikrein bind to the sulfatide surface, whereas no binding of the light chain of kallikrein was detectable. Since the effects of pH and ionic strength on sulfatide-dependent Factor XII activation by kallikrein can be explained by effects on kallikrein binding to sulfatides we conclude that surface-bound Factor XII is activated by surface-bound kallikrein. Our data suggest that sulfatides stimulate Factor XII activation via two distinct mechanisms: a) by making Factor XII more susceptible to proteolytic cleavage and b) by promoting the formation of the enzyme-substrate complex through surface binding of both kallikrein and factor XII.
D004789:Enzyme Activation; D005174:Factor XII / Q000378:metabolism*; D015956:Factor XIIa; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D010446:Peptide Fragments / Q000378:metabolism
D046911:Macromolecular Substances; D010446:Peptide Fragments; D005174:Factor XII; D007610:Kallikreins; D015956:Factor XIIa