AJP - Cell Physiology, Vol 251, Issue 5 795-C802, Copyright © 1986 by American Physiological Society
Importance of purine nucleotide cycle to energy production in skeletal muscle
W. F. Flanagan, E. W. Holmes, R. L. Sabina and J. L. Swain
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 production was again impaired in the AICAriboside-treated
animals, but lactate production was similar in both groups. These findings
suggest the loss of the initial aerobic component of energy generation in
tetanically stimulated muscle of AICAriboside-treated animals. The results
of this study indicate that disruption of the purine nucleotide cycle at
the level of the synthetase and lyase reactions is associated with skeletal
muscle dysfunction, and suggest that the cycle plays an anapleurotic role
in providing citric acid cycle intermediates that enhance aerobic energy
production in contracting skeletal muscle.
