Incubation of C1 esterase inhibitor with Crotalid, Viperid and Colubrid snake venoms resulted in enzymatic inactivation of the inhibitor. Intact inhibitor (104 kDa) was converted into an active ...intermediate species of 89 kDa and then a further cleavage resulted in formation of an 86-kDa inactive inhibitor. In contrast, C1 esterase inhibitor did not lose activity during incubation with Elapid venoms; however, the intact inhibitor was gradually converted to an active species of 89 kDa during the incubation. Human alpha 1-antichymotrypsin was inactivated by all venoms tested, including those from the Elapid family. The 67-kDa intact inhibitor was converted by the venom proteinases to an inactive 63-kDa form. The results suggest that this acute-phase plasma protein is readily susceptible to inactivation by venom proteinases. Human alpha 2-antiplasmin (68 kDa) was cleaved to form a 61-kDa active intermediate, which then underwent a second cleavage to produce an inactive 53-kDa product. Elapid venoms had no effect on alpha 2-antiplasmin activity and did not cleave this inhibitor. All inhibitors were inactivated with catalytic amounts of venom proteinases. No stable proteinase-proteinase inhibitor complexes were detected, and no random proteolysis of the inhibitors occurred.
Proteinase II from Crotalus adamanteus venom formed a complex with human alpha 2-macroglobulin in which approx. 1.7 mol of enzyme were bound per mol inhibitor. The complex did not enzymatically ...inactivate human alpha 1 proteinase inhibitor. However, active proteinase II was released from the complex in the presence of a high molecular weight proteinase fraction from C. adamanteus venom. The alpha 2-macroglobulin-proteinase II complex was also unstable during incubation in serum, and the enzyme released from the complex caused inactivation of serum proteinase inhibitors. The results indicate conditions under which venom proteinases can be dissociated from their complexes with alpha 2-macroglobulin and thus remain functional in the presence of molar excesses of inhibitor.
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