OPERATION OF THE PURINE NUCLEOTIDE CYCLE IN ANIMAL TISSUES

1. The operation of the purine nucleotide cycle, consisting of the enzymes adenylate deaminase (E.C. 3.5.4.6), adenylosuccinate synthetase (E.C. 6.3.4.4) and adenylosuccinate lyase (E.C. 4.3.2.2), has been reviewed with reference to its metabolic function in animal tissues.
2. Abundant evidence, both from in vitro and in vivo studies, suggests that the purine nucleotide cycle serves to stabilize the adenylate 'energy charge' (or 'phosphorylation potential') in the cytoplasm of vertebrate cells during a temporary imbalance between ATP-consumption and ATP-production. This stabilization, however, is absent or much less efficient in tissues of invertebrates.
3. The hypothesis that AMP-deaminase is involved in the regulation of glycolysis is not supported by recent work. In a variety of cell types, including skeletal muscle and blood platelets, blocking of AMP-deaminase activity (due to a genetic defect or to pharmacological inhibition) is without effect on the glycolytic rate. Detailed kinetic and histochemical analysis of energy metabolism shows lack of correlation between AMP-deaminase activity and glycolysis in skeletal muscle during exercise.
4. The purine nucleotide cycle appears to control the level of citric acid cycle intermediates in skeletal muscle. Pharmacological inhibition of adenylosuccinate lyase or adenylosuccinate synthetase leads to a reduced availability of four-carbon 'sparker' molecules to the Krebs cycle with a concomitant impairment of aerobic energy production during muscular work.
5. The cycle appears to be a major pathway for amino acid deamination in skeletal muscle and brain of vertebrates, but not in kidney or liver.