Mode of Action of Rat Liver Phosphodiesterase on a Polymer of Phosphoribosyl Adenosine Monophosphate and Related Compounds

Pyrophosphatase activity of rat liver phosphodiesterase, which forms nucleoside 5'-monophosphates, was studied. Evidence is presented that NADH, adenosine 5'-diphosphate ribose, and a polymer of phosphoribosyl-AMP (poly (ADPR)) were hydrolyzed by this enzyme. The mode of action of the enzyme on poly ADPR was studied. 1. The enzyme hydrolyzed poly ADPR to produce the same product as was formed by phosphodiesterase from snake venom. 2. Kinetic studies suggest that both the phosphodiester compounds, p-nitrophenyl urinine 5'-monophosphate and poly ADPR, were hydrolyzed by the same site or by overlapping active sites. 3. Poly ADPR was not hydrolyzed randomly, but rather in an exonucleolytic fashion. Little DNA or RNA was hydrolyzed by an amount of enzyme sufficient to decompose half the initial amount of the substrate, poly ADPR.