Importance of purine nucleotide cycle to energy production in skeletal muscle

1986 ◽  
Vol 251 (5) ◽  
pp. C795-C802 ◽  
Author(s):  
W. F. Flanagan ◽  
E. W. Holmes ◽  
R. L. Sabina ◽  
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.

1984 ◽  
Vol 56 (2) ◽  
pp. 520-525 ◽  
Author(s):  
G. A. Brooks ◽  
C. M. Donovan ◽  
T. P. White

o assess the effects of gradient and running speed on efficiency of exercise, and to evaluate contributions of oxidative and anaerobic energy production (Ean) during locomotion, two sets of experiments were performed. The caloric expenditures of rats were determined from O2 consumption (VO2) while they ran at three speeds (13.4, 26.8, and 43.1 m/min) on five grades (1, 5, 10, 15, and 20%). In addition, lactate turnover (LaT) and oxidation (Laox) were determined on rats at rest or during running at 13.4 and 26.8 m/min on 1% grade, respectively. Lactate production not represented in the VO2 (i.e., Ean) was calculated from the LaT not accounted for by oxidation [(LaT an) = LaT-Laox)]. The Ean was calculated as: Ean = [LaT an(mumol/min)] [1.38 ATP/La] [11 mcal/mumol ATP]. Gross efficiency of exercise (the caloric equivalent of external work/caloric equivalent of VO2 X 100) ranged from 1.7 to 4.5%. Apparent efficiency (the inverse of the regression of caloric equivalent of VO2 on the caloric equivalent of work X 100) ranged from 20.5 to 26.4% and reflected the metabolic response of rats to applied external work. The contribution of Ean to total energy turnover ranged from 1.6% at rest to 0.8% during running at 13.4 m/min on a 1% grade. Despite active LaT during steady-state exercise, Ean contributes insignificantly to total energy transduction, because over 70% of the lactate produced is removed through oxidation. VO2 adequately represents metabolism under these conditions.


1992 ◽  
Vol 70 (1) ◽  
pp. 132-141 ◽  
Author(s):  
T. E. Graham ◽  
D. A. MacLean

This review focuses on the ammonia and amino acid metabolic responses of active human skeletal muscle, with a particular emphasis on steady-state exercise. Ammonia production in skeletal muscle involves the purine nucleotide cycle and the amino acids glutamate, glutamine, and alanine and probably also includes the branched chain amino acids as well as aspartate. Ammonia production is greatest during prolonged, steady state exercise that requires 60–80% [Formula: see text] and is associated with glutamine and alanine metabolism. Under these circumstances it is unresolved whether the purine nucleotide cycle (AMP deamination) is active; if so, it must be cycling with no IMP accumulation. It is proposed that under these circumstances the ammonia is produced from slow twitch fibers by the deamination of the branched chain amino acids. The ammonia response can be suppressed by increasing the carbohydrate availability and this may be mediated by altering the availability of the branched chain amino acids. The fate of the ammonia released into the circulation is unresolved, but there is indirect evidence that a considerable portion may be excreted by the lung in expired air.Key words: glutamine, branched chain amino acids, glutamate dehydrogenase, purine nucleotide cycle.


1985 ◽  
Vol 249 (6) ◽  
pp. R699-R703 ◽  
Author(s):  
S. L. Lindstedt ◽  
H. Hoppeler ◽  
K. M. Bard ◽  
H. A. Thronson

All skeletal muscle can produce roughly the same maximal cross-sectional force; however, the power (energy X time-1) required to develop and maintain that force increases with increasing contraction velocity. Thus the rate of muscle tension development may be of primary importance in setting the energy demand of contracting muscle. We have estimated the rate of muscle shortening during terrestrial locomotion in mammals as a function of body mass. The rate of muscle shortening of the knee extensors is much faster in small than large mammals, scaling in proportion to the -0.23 power of mass. This exponent suggests a constant body size-independent relation among skeletal muscle: O2 consumption, mitochondria content, myosin ATPase activity, and in vivo shortening velocity.


1982 ◽  
Vol 38 (9) ◽  
pp. 1035-1037 ◽  
Author(s):  
P. W. D. Ścisłowski ◽  
Z. Aleksandrowicz ◽  
J. Świerczyński

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