Snake Venom Nucleases, Nucleotidases, and Phosphomonoesterases

Abstract

Snake venom components, acting in concert within prey, cause immobilization and initiate diges- tion. Additional pharmacological activities have evolved among several hydrolytic enzymes of snake venom, which interfere with numerous physiological processes of the prey and which pro- duce these effects. However, hydrolytic enzymes such as nucleases (DNase, RNase, and phospho- diesterase), 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 defined. Also, they show overlapping substrate specificities 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 specificities with phosphodiesterase. The dif- ferences among them are still not clear, and analyzing cDNA or amino acid sequences of the puri- fied 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 metallo- enzymes. 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 significant role for these enzymes in envenomation. It is suggested that their major function may be in the generation of adenosine, a multitoxin. Adenosine generated in vivo by their synergistic action on endogenous substrates is known to bring about various phar- macological 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- fied by pharmacological studies using purified enzymes. Further research is needed to characterize the biological roles of these enzymes in snake venoms and to establish clearly their role in enveno- mation sequelae