Modification of the skeletal muscle energy metabolism induced by intermittent normobaric hypoxia and treatment with biological pyrimidines.
Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate), Krebs cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate), related free amino acids (glutamate, alanine), ammonia, energy store (creatine phosphate), energy mediators (ATP, ADP, AMP) and energy charge potential were evaluated. Furthermore the maximum rate (Vmax) of the following enzyme activities was evaluated in the crude extract and/or mitochondrial fraction: for the anaerobic glycolytic pathway: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; for the tricarboxylic acid cycle: citrate synthase, malate dehydrogenase; for the electron transfer chain: total NADH cytochrome c reductase, cytochrome oxidase. The rat gastrocnemius muscles were analysed in normoxia and after normobaric intermittent hypoxia (12 hours continuously daily; for 5 days). Cytidine and/or uridine were administered daily at the dose of 120 mg/kg, i.p., 30 min before the beginning of the experimental hypoxia. The intermittent normobaric hypoxia induced a biochemical adaptation characterized by the decrease of the muscular contents of creatine phosphate, citrate, alpha-ketoglutarate and glutamate. This adaptation occurred in the absence of significant changes in the Vmax of the tested muscle enzymes. In gastrocnemius muscle from hypoxic rats, the two biological pyrimidines tested induced various discrete, but often related, modifications of the contents of some Krebs cycle intermediates (i.e., alpha-ketoglutarate, malate) and related free amino acids (i.e., glutamate, alanine). In any case, the treatment with cytidine and/or uridine did not modify the Vmax of marker enzymes related to energy transduction.
D000222:Adaptation, Physiological; D000818:Animals; D001711:Biotransformation; D003562:Cytidine / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014529:Uridine / Q000494:pharmacology
D011743:Pyrimidines; D003562:Cytidine; D014529:Uridine