The kallikrein-like activity of Heloderma venom is inhibited by carbon monoxide

Vance G. Nielsen, Nathaniel Frank

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)533-539
Number of pages7
JournalJournal of Thrombosis and Thrombolysis
Issue number4
StatePublished - May 15 2019


  • Carbon monoxide
  • Heme
  • Kallikrein-like activity
  • Phospholipase A
  • Thrombelastography

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine


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