the kallikrein-like activity of heloderma venom is inhibited by carbon monoxide

Lizards in the genus heloderma are the most ancient venomous reptiles, with a traceable lineage nearly 100 million years old. the proteome of the venom of three of the remaining species (heloderma suspectum, h. exasperatum, h. horridum) are very conserved, with kallikrein-like activity present to cause critical hypotension to immobilize and outright kill prey. kallikrein-like activity would be expected to activate the contact protein pathway of coagulation, which would be detectable with thrombelastography in human plasma. thus, it was proposed to determine if kallikrein-like activity could be detected with thrombelastography, and if this activity could be inhibited by carbon monoxide (co) via a putative heme-based mechanism. procoagulant activity of each venom was assessed via thrombelastography with normal plasma, and kallikrein-like activity confirmed with fx-depleted plasma. venom was then exposed to carbon monoxide releasing molecule-2 (corm-2) or its inactive releasing molecule to assess co inhibition. all three venoms demonstrated kallikrein-like activity with the same potency and inhibition of activity by co. in conclusion, the present work documented that procoagulant, kallikrein-like activity containing venoms of the oldest species of venomous reptiles was inhibited by co, potentially via heme modulation. this is also the first identification and characterization of a kallikrein-like enzyme utilizing coagulation factor-depleted plasma to assess venom that inflicts hypotension. future investigations will continue to define the vulnerability of venom enzymatic activities to co.