Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic administration of the NADH-CoQ reductase inhibitor, diphenyleneiodonium to rats at two dose levels, 1.0 and 1.5 mg/kg per day, caused a 40% and 60% reduction, respectively, in the in vitro rate of NAD-linked respiration by skeletal muscle mitochondria. At the highest dose, muscle fatigue, lactic acidosis and an over-utilization of phosphocreatine was observed in the gastrocnemius muscle during mild stimulation of 1 Hz frequency. The resynthesis of phosphocreatine following muscle stimulation was about 2 fold slower in the treated animal group. At the low dose, no significant biochemical changes were observed during muscle stimulation at 4 Hz. The results are discussed in terms of skeletal muscle "oxidative reserve", twitch tension maintenance and the relevance to the human diseased state of mitochondrial myopathy.
 ...
PMID:An animal model of mitochondrial myopathy: a biochemical and physiological investigation of rats treated in vivo with the NADH-CoQ reductase inhibitor, diphenyleneiodonium. 312 47

Mitochondrial myopathies are a clinical condition characterized by muscle weakness and fatigue in which the primary defect is localized at the level of the mitochondria. Microscopic examination shows accumulations of mitochondria at the fibre periphery (ragged red fibres) and in some cases mitochondrial paracrystalline inclusions. The spectrum of different mitochondrial defects so far described is reviewed and data from cases investigated in this laboratory are described. The first case was a 17-year-old boy with a multisystem disorder whose muscle mitochondria showed low respiratory activity with all substrates, which doubled in the presence of uncoupler. Further investigation showed that the mitochondrial ATPase activity was only 6% of normal. The next cases were a mother and daughter who showed a typical lipid storage myopathy. The latter was treated successfully with oral carnitine but the myopathy persisted. Mitochondrial investigations indicated a low respiratory activity with NAD-linked substrates but normal activity with succinate and ascorbate + TMPD. A defect in the NADH-CoQ reductase section of the respiratory chain was pinpointed possibly at an iron-sulphur centre. The fourth and fifth cases were two sisters who exhibited no lipid storage myopathy but whose mitochondrial activity was low with NAD-linked substrates but normal with succinate. Again a defect in the NADH-CoQ reductase (complex I) of the respiratory chain was determined. They were also investigated using 31P-NMR. It was found after exercise that their muscle creatine phosphate levels took seven times longer to return to pre-exercise concentrations than control subjects. These results are discussed with respect to the synthesis of mitochondrial proteins and the influence that both the mitochondrial and nuclear DNA have on this process.
 ...
PMID:Mitochondrial myopathies: disorders of the respiratory chain and oxidative phosphorylation. 643 47