ABSTRACT
Snake venom components, acting in concert within prey, cause immobilization and initiate digestion. Additional pharmacological activities have evolved among several hydrolytic enzymes of snake venom, which interfere with numerous physiological processes of the prey and which produce these effects. However, hydrolytic enzymes such as nucleases (DNase, RNase, and phosphodiesterase), nucleotidases (5′ nucleotidase, ATPase, and ADPase), and phosphomonoesterases (acid and alkaline phosphomonoesterases) have not been extensively studied, and their pharmacological roles in venoms are not clearly dened. Also, they show overlapping substrate specicities and have other biochemical properties in common, producing uncertainty about their individual identity in venoms. For example, DNases, RNases, and phosphodiesterase share similar properties in substrate hydrolysis but differ in their pH optima and metal ion requirement for activity. Nucleotidases such as ATPases and ADPases have overlapping substrate specicities with phosphodiesterase. The differences among them are still not clear, and analyzing cDNA or amino acid sequences of the puri-ed enzymes is necessary to resolve these differences (if any). Except for RNases, most of these enzymes are of high molecular weight, and all except DNases and RNases are known to be metalloenzymes. Of these, only 5′ nucleotidases and ADPases are known to be involved in inhibition of platelet aggregation and blood coagulation. However, the near-ubiquitous distribution of these enzymes in venoms suggests a signicant role for these enzymes in envenomation. It is suggested that their major function may be in the generation of adenosine, a multitoxin. Adenosine generated
I. Introduction .......................................................................................................................... 156 II. Nucleases .............................................................................................................................. 157 A. DNases (E.C. 3.1.21.1) .................................................................................................... 157 B. RNases (E.C. 3.1.21.-) ..................................................................................................... 157 C. Phosphodiesterase (EC. 3.1.4.1) ...................................................................................... 158 III. Nucleotidases ........................................................................................................................ 160 A. 5ʹ Nucleotidase (E.C. 3.1.3.5) ......................................................................................... 161 B. ATPases (E.C. 3.6.1.-) ..................................................................................................... 163 C. ADPases (E.C. 3.6.1.-) .................................................................................................... 163 IV. Phosphomonoesterases ......................................................................................................... 163 V. Adenosine Liberation Due to the Action of Nucleases/Nucleotidases/
Phosphomonoesterases ......................................................................................................... 164 VI. Conclusions .......................................................................................................................... 167 Acknowledgments .......................................................................................................................... 167 References ...................................................................................................................................... 167
in vivo by their synergistic action on endogenous substrates is known to bring about various pharmacological effects, similar to those induced by the whole venom. Therefore, it appears that these enzymes play a central role in liberating adenosine, and through the action of adenosine, assist in prey immobilization. In addition, these enzymes could possess other pharmacological activities, which can interfere in diverse physiological processes of the prey/victim, but this has not been veri-ed by pharmacological studies using puried enzymes. Further research is needed to characterize the biological roles of these enzymes in snake venoms and to establish clearly their role in envenomation sequelae.
