Importance of purine nucleotide cycle to energy production in skeletal muscle

The purpose of this study was to determine the role of the purine nucleotide cycle in aerobic energy production. Rats received either saline or 5-amino-4-imidazolecarboxamide riboside (AICAriboside), a precursor to an inhibitor of adenylosuccinate lyase (AICAR). Muscle tension was quantified during gastrocnemius stimulation, and muscle metabolite content was measured to obtain an estimate of the activity of the enzymes of the cycle. AICAriboside prevented the increase in synthetase and lyase activities observed in control animals during moderate (aerobic) stimulation, and was accompanied by marked muscle dysfunction. Although glycolytic energy production was not impaired in the AICAriboside-treated animals (lactate production occurred), total energy production did not meet energy demand. These results suggest that disruption of the purine nucleotide cycle impairs aerobic energy metabolism. Tetanic (anaerobic) stimulation produced more rapid fatigue in the AICAriboside-treated group. Total energy productio...