An Iron-Dependent 5'-Nucleotide Phosphoribohydrolase Activity in the Venom of Crotalus atrox and Its Effect upon the Determination of Mammalian Ribonucleotide Reductase

Abstract

There is an iron-dependent activity in the venom of Crotalus atrox which appears to hydrolyze the N-glycosidic sugar-base bond of pyrimidine and purine nucleotides. Maximal activation of this activity occurred at 1.0 mmol/1 and 0.8 mmol/1 FeCl(3) for cytidine diphosphate (CDP) and ADP substrates, respectively. The release of free base affects the background values of control experiments carried out during nucleotide-labelled assays of ribonucleotide reductase which require the conversion of nucleotides to nucleosides by snake venom treatment. When the reductase is examined in intact cells, a situation closely resembling normal physiological conditions for the enzyme, FeCl(3) was found to be an inhibitor of ADP reductions and varied from a mild stimulator to a significant inhibitor of CDP reductions depending upon FeCl(3) concentration. Possible explanations for previously observed variability in ribonucleotide reductase activity in the presence of iron are suggested.