A model to explain the pharmacological effects of snake venom phospholipases A2.
Snake venom phospholipase A2 enzymes induce a wide variety of pathological symptoms in animals, despite sharing a common catalytic activity and similar structural features with nontoxic mammalian pancreatic enzymes. A hypothetical model is described to explain how specific pharmacological effects, such as presynaptic neurotoxicity, cardiotoxicity, myotoxicity, anticoagulant and platelet effects are exhibited by venom PLA2 enzymes. The model is an effort to elucidate many controversial and contradictory observations which have previously been difficult to interpret. The essential feature of the model is the targeting of venom PLA2 enzymes to the specific tissue or cell due to their affinity towards specific proteins, rather than lipid domains. After the initial binding, PLA2 enzymes induce various pharmacological effects by mechanisms which are either dependent or independent of their enzymatic activity. The model and its predicted target proteins thus provide a new focus for toxin research.
Kini
R M
RM
Department of Biochemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Evans
H J
HJ
D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D008954:Models, Biological; D009420:Nervous System / Q000187:drug effects; D010740:Phospholipases / Q000633:toxicity*; D010741:Phospholipases A / Q000633:toxicity*; D054467:Phospholipases A2; D012910:Snake Venoms / Q000633:toxicity*
D012910:Snake Venoms; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2