Operation of the Purine Nucleotide Cycle in Animal Tissues

Abstract

Summary 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.

Vitamin C Deficiency Activates the Purine Nucleotide Cycle in Zebrafish

“…The production of ammonia from this reaction has been hypothesized to independently regulate energy metabolism by preventing the inhibition of phosphofructokinase by citrate, stimulating glycolytic flux (27). As an integral part of the PNC, AMPD is an energy-generating pathway operative in many animal tissues (35). In goldfish muscle, AMPD exists in the free or bound forms (24).…”

AMP deaminase histochemical activity and immunofluorescent isozyme localization in rat skeletal muscle.

“…The potential activity of the AMPda in these sites is tightly regulated, and it is estimated as only 15% activated at rest (Ronca-Testoni et al, 1979). This tight regulation is exemplified by the range in apparent Km values for AMP cited by Ogasawara et al (1980) (van Waarde, 1988). Therefore, AMPda-A, although intrinsically less activated, has a greater activity range and is more 944 THOMPSON, SABINA, OGASAWARA, RILEY responsive to regulators than AMPda-C, particularly when bound to myosin.…”

Regulation of AMP Deaminase by Phosphoinositides

“…AMPD is also a component of the purine nucleotide cycle, an energy-generating pathway reportedly operative in many animal tissues (reviewed in Ref. 12). The AMPD1 gene encodes human isoform M and rat isoform A (13); the AMPD2 gene encodes the human isoform L and rat isoform B (14,15); and the AMPD3 gene encodes the human isoform E and the rat isoform C (16,17).…”