The pharmacological role of nucleotidases in snake venoms

Abstract

Several hydrolytic enzymes of snake venom have evolved to interfere in various physiological processes, which are well defined. However, hydrolytic enzymes such as nucleotidases (5'nucleotidase, ATPase, and ADPase) are less studied and their pharmacological role in venoms is not clearly defined. Very few studies have shown the pharmacological importance of these endogenous purine release related enzymes in venoms. The near-ubiquitous distribution of these enzymes in venoms, suggests a significant role for these enzymes in envenomation. It is suggested that their major function is in the generation of purines (mainly adenosine)-a multitoxin. Therefore, it appears that these enzymes play a central role in liberating adenosine and through the action of adenosine help in prey immobilization. However, apart from this, these enzymes could also possess other pharmacological activities. Further research is needed to biologically characterize these enzymes in snake venoms, such that their role in venom is clearly established.

Evidence for existence of venom 5′ nucleotidase in multiple forms through inhibition of concanavalin A

“…Recently from our lab, with the help of specific inhibitor of venom 5′ nucleotidase we demonstrated the enzyme's involvement in inducing anticoagulant effect of Naja naja venom 4. It is hypothesized that 5′ nucleotidase is involved in snake envenomation strategies through liberation of purines – a multitoxin;1, 5 however, experimental evidences are lacking in elucidating the pharmacological actions. The reason for this is the amount of protein 5′ nucleotidase present in venoms which is <0.3% (personal observation), added to this their is loss of protein during purification process which renders the scientists working on characterization aspect of having less amount of purified enzyme for complete biochemical and pharmacological characterization of venom 5′ nucleotidase.…”

“…The reason for this is the amount of protein 5′ nucleotidase present in venoms which is <0.3% (personal observation), added to this their is loss of protein during purification process which renders the scientists working on characterization aspect of having less amount of purified enzyme for complete biochemical and pharmacological characterization of venom 5′ nucleotidase. As a result literature survey on venom 5′ nucleotidase indicates that it has been less characterized in snake venom 1, 2, 5. Concanavalin‐A (Con‐A) is a lectin used as a biochemical tool to differentiate enzymes/toxins as glycoproteins from different sources 4.…”

Proteomic Analyses of Agkistrodon contortrix contortrix Venom Using 2D Electrophoresis and MS Techniques

“…5′-nucleotidases act as co-factors for hemorrhagic toxins and inhibit platelet aggregation by releasing the adenosine from the GMP and AMP, which binds to the receptors on the platelets [24]. Thus, these proteins act synergistically to phospholipases A 2 and disintegrins enhancing anticoagulant effect of the venom [27,28,29]. 5′-nucleotidases are an unexplored group of proteins, both in terms of toxicological and pharmacological effects.…”

Proteomic analysis of the rare Uracoan rattlesnake Crotalus vegrandis venom: Evidence of a broad arsenal of toxins

“…1). Although E5 0 N biological activity and further role in snake venom are not well understood, the presence of free purines supports the potential of venom-induced hypotension and paralysis via purine receptors (Dhananjaya and D'Souza, 2010). According to Hart et al (2008) E5 0 N can inhibit platelet aggregation.…”