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Pseudechis porphyriacus venom procoagulant and anticoagulant enzymes

Molecular classification
Enzyme, Phospholipase A2, Serine protease, Prothrombin activator
01

Overview

Pseudechis porphyriacus venom procoagulant and anticoagulant enzymes are a complex suite of toxins found in the venom of the Red-bellied Black Snake (Pseudechis porphyriacus). The anticoagulant activity is primarily driven by Phospholipase A2 (PLA2) enzymes, specifically a group of isoenzymes known as Pseudexin (A, B, and C), which inhibit the prothrombinase complex by targeting Factor Va or preventing its assembly (Lane et al., 2011; Vaughan et al., 1981). Uniquely among the Pseudechis genus, P. porphyriacus also contains procoagulant enzymes, specifically a mutated Factor Xa-like serine protease that acts as a prothrombin activator, although its activity is relatively weak compared to other Australian elapids (Zdenek et al., 2019; St Pierre et al., 2005). In clinical envenomation, these enzymes lead to an anticoagulant coagulopathy, typically manifested as a prolonged activated partial thromboplastin time (aPTT), and can also cause systemic myotoxicity and local tissue damage (Churchman et al., 2010). Therapeutic management involves the administration of Tiger Snake or Black Snake antivenoms, which effectively neutralize these enzymatic activities (Ramasamy et al., 2011). Recent research also highlights the potential of small-molecule inhibitors like Varespladib to neutralize the PLA2-mediated anticoagulant and myotoxic effects (Zdenek et al., 2020).

Other names
Red-bellied black snake venom enzymesPseudexinPseudechis porphyriacus prothrombin activatorRBBV procoagulant/anticoagulant toxinsPseudechis porphyriacus Factor Xa-like enzyme
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Mechanism of action

Antivenoms function by immunologically binding and neutralizing the venom enzymes, preventing their interaction with blood clotting factors such as prothrombin and Factor Va (Ramasamy et al., 2011). Small molecule inhibitors like Varespladib (LY315920) specifically target and inhibit the enzymatic activity of phospholipase A2 toxins, thereby preventing phospholipid hydrolysis and subsequent anticoagulant or myotoxic effects (Zdenek et al., 2020).

03

Biological functions

Blood coagulationProteolysisPhospholipid hydrolysisHemostasis
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Disease associations

Snake envenomationCoagulopathyMyotoxicity
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Safety considerations

Antivenom-induced anaphylaxisSerum sicknessVenom-induced myotoxicityAcute kidney injuryAnticoagulant coagulopathy
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Interacting drugs

Tiger snake antivenom

2 more in the full profile.

07

Biomarkers

Activated partial thromboplastin time (aPTT)Creatine kinase (CK)Prothrombin time (PT)Venom concentration

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