Kallikreins autoactivation

The various interactions of the constituents required for the formation of bradykinin are shown in figure 2. The initiating step is a slow autoactivation of factor XII [10]. However, once this has occurred and prekallikrein is converted to kallikrein, there is... 

Factor Xlla converts prekallikrein to kallikrein and kallikrein cleaves HK to generate bradykinin. There is also an important positive feedback in the system in which the kallikrein generated rapidly converts unactivated factor XII to activated factor XII, and the rate of this reaction is hundreds of times faster than the rate of autoactivation [11]. Therefore, much of the unactivated factor XII can be cleaved and activated by kallikrein. Cl inhibitor inhibits all functions of factor Xlla and it is one of two major plasma kallikrein inhibitors. Thus all functions of kallikrein are also inhibited, including the feedback activation of factor XII, the cleavage of HK, and the activation of plasma pro-urokinase [66] to lead to plasmin formation. Cl inhibitor also inhibits the fibrinolytic enzyme plasmin, although it is a relatively minor inhibitor compared to a2-antiplasmin or a2-macroglobulin. 

Mikolajczyk SD, Millar LS, Marker KM, et al. Ala217 is important for the catalytic function and autoactivation of prostate-specific human kallikrein 2. Eur J Biochem 1997 246 440 146. 

Similarly, both the contact and coagulation systems are triggered by FXn, which is conformationally changed by contact activation. FXn in the initially adsorbed plasma protein layer is autoactivated to form FXIIa by this interaction. As mentioned in Section 4.4, this enzyme then cleaves PK into kallikrein, which cleaves fluid-phase FXII into FXIIa, thereby creating a positive feedback loop. 

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