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

Isolated extensor digitorum longus muscles from rat were exposed to atmospheres of 30% CO2 (high-CO2 muscles) or 6.5% CO2 (control muscles) in O2 for 95 min. Muscle contraction characteristics were studied before and after the incubation. Tetanic tension decreased in high-CO2 muscles to 55% of initial value but remained unchanged in control muscles. Relaxation time was prolonged in high-CO2 muscles but not in control muscles. Intracellular pH was 6.67 +/- 0.04 (SD) in high-CO2 muscles and 7.01 +/- 0.04 in control muscles. CO2-induced acidosis had a marked influence on the intermediary energy metabolism as shown by a fourfold increase of glucose 6-phosphate, a 14% increase of ADP, and a decrease of phosphocreatine to 44% of the control value. Lactate and pyruvate contents were unchanged. The observed metabolic changes can be explained by an effect of H+ on the activity of phosphofructokinase and on the creatine kinase equilibrium. It can be concluded that H+ concentration causes muscular fatigue. It is, however, uncertain whether this is an effect of increased H+ per se or by high-energy phosphate depletion induced by acidosis.
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PMID:Fatigue and phosphocreatine depletion during carbon dioxide-induced acidosis in rat muscle. 640 27

Mechanical and metabolic relationships of muscle lacking phosphofructokinase (PFKD) activity were compared with muscle having normal phosphofructokinase (NORM) activity by using the gastrocnemius-plantaris muscle group with isolated circulation in situ. Muscle contractile properties were similar in both groups. Initial power output (W) during repetitive tetanic (200 ms, 50 impulses/s) isotonic contractions was similar in both groups; however, W declined significantly more (30-80%) in PFKD than in NORM muscle over time, with a constant O2 uptake (VO2)/W. Despite similar O2 and substrate delivery, PFKD muscle had a lower VO2 (42-55%), less glucose uptake, similar free fatty acid uptake, and lactic acid uptake rather than output, during contractions. Muscle venous H+ concentration, strong ion difference, and PCO2 increased during contractions, the magnitude of change being smaller in PFKD muscle. Elevating arterial lactate concentration before contractions in PFKD muscle resulted in significant improvements in W and VO2 without altering the acid-base exchange at the muscle. Increasing O2 delivery by increasing arterial O2 concentration in PFKD dogs did not improve W or VO2. We conclude that, despite no inherent mechanical or contractile differences, PFKD muscle has a severely limited oxidative capacity and exaggerated fatigue and blood flow responses to contractions due to limited substrate metabolism resulting from the inability to utilize glycogen and/or glucose.
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PMID:Metabolic and work capacity of skeletal muscle of PFK-deficient dogs studied in situ. 786 69

The use of MRS has become more widespread as cost and availability have improved. It has been demonstrated that MRS of human skeletal muscle can play a significant role in (1) understanding healthy muscle metabolism and the mechanisms of muscle fatigue, (2) understanding the effects of disease on muscle metabolism and function, (3) monitoring the efficacy of therapeutic intervention, and (4) the confirmation of disease diagnoses. The results of the 31P MRS studies of disease are summarized in the Table 1. A few conditions (McArdle's, PFK deficiency) are associated with failure to develop acidosis during exercise. This response appears to be relatively specific to these metabolic myopathies. For most of the conditions reviewed here, however, the metabolic findings of reduced PCr/Pi and greater acidosis during exercise with impaired recovery of PCr/Pi and pH are very similar. The nonspecificity of the MRS results suggests the possibility that a common mechanism may be at work in all of these diseases. A major question to arise from clinical studies using MRS concerns the extent to which deconditioning may have played a role in some of these findings. This is because conditions associated with muscle weakness, rapid fatiguability, and muscle pain during or following vigorous physical activity may also be those that lead to deconditioning. In virtually all studies reviewed here, healthy, active subjects were used as controls. There are no examples in which controls were appropriately matched to the subjects for their level of conditioning. Conditioning could be assessed by questionnaire, activity logs, activity monitoring devices, or measurements of conditioning effects such as maximal oxygen consumption. The role of deconditioning in the decreased quality of life of persons with chronic diseases has not been fully explored. Future studies of chronic disease using MRS should combine MRS with other techniques to further probe the mechanisms of muscle metabolism under various conditions, and the extent to which these mechanisms are sensitive to the level of physical conditioning.
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PMID:Magnetic resonance spectroscopy studies of human muscle. 814 Feb 29

Pharyngeal muscles play important roles in the maintenance of upper airway patency during sleep. The present study determined the extent of heterogeneity among pharyngeal muscles and the diaphragm in their metabolic profiles, and examined whether differences among muscles may account for previously described differences in their fatigue resistance. Cat and rat sternohyoid, geniohyoid, genioglossus (cat only) and diaphragm muscle were assayed for activities of the mitochondrial enzyme citrate synthase (CS), the glycolytic enzyme phosphofructokinase (PFK) and the cytosolic enzyme lactate dehydrogenase (LDH). CS activity varied among muscles in both species, being highest for genioglossus in cat and highest for diaphragm in rat. PFK activity was highest for genioglossus in cat, but did not differ among muscles in rat. LDH activity was lower for the genioglossus than the sternohyoid and diaphragm in cat. CS and PFK activities correlated positively, and LDH activity correlated negatively, with in vitro fatigue resistance assessed after 5 min of repetitive stimulation in cat. These data indicate close relationships between metabolic profiles, particularly oxidative capacity, and fatigue resistance of pharyngeal muscles in relationship to each other and to the diaphragm.
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PMID:Metabolic profiles of cat and rat pharyngeal and diaphragm muscles. 893 Nov 76

Skeletal muscle buffering capacity (beta m), enzyme activities and exercise performance were measured before and after 4 weeks of high-intensity, submaximal interval training (HIT) undertaken by six well-trained competitive cyclists [mean maximal oxygen consumption (VO2max) = 66.2 ml.kg-1.min-1]. HIT replaced a portion of habitual endurance training and consisted of six sessions, each of six to eight repetitions of 5 min duration at 80% of peak sustained power output (PPO) separated by 1 min of recovery. beta m increased from 206.6 (17.9) to 240.4 (34.1) mumol H+.g muscle dw-1.pH-1 after HIT (P = 0.05). PPO, time to fatigue at 150% PPO (TF150) and 40-km cycle time trial performance (TT40) all significantly improved after HIT (P < 0.05). In contrast, there was no change in the activity of either phosphofructokinase or citrate synthase. In addition, beta m correlated significantly with TT40 performance before HIT (r = -0.82, P < 0.05) and the relationship between change in beta m and change in TT40 was close to significance (r = -0.74). beta m did not correlate with TF150. These results indicate that beta m may be an important determinant of relatively short-duration (< 60 min) endurance cycling activity and responds positively to just six sessions of high-intensity, submaximal interval training.
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PMID:Skeletal muscle buffering capacity and endurance performance after high-intensity interval training by well-trained cyclists. 900 51

This study examined whether training under normobaric hypoxic conditions (simulating medium level altitude) would enhance physical performance and selected muscle adaptations over and above that which occurs with normoxic training. Ten healthy males (19-25 yr) underwent 8 wk of unilateral cycle ergometry training so that one leg was trained while breathing an inspirate of 13.5% O2 and the other while breathing normal ambient air. Pre- and post-training measurements included single leg VO2max and time to fatigue at 95% VO2max. Needle biopsies from quadriceps were assayed for oxidative and glycolytic enzyme activity and analyzed for capillary density, fiber area, % fiber type, and mitochondrial and lipid volume density. VO2max, time to fatigue, citrate synthase (CS), succinate dehydrogenase, and phosphofructokinase activity increased significantly (P > 0.05) in both legs following training. The increase in CS activity in the hypoxically trained leg was also significantly greater than that in the normoxically trained leg. It thus appears that training under moderate normobaric hypoxic conditions enhances muscle citrate synthase activity to a greater extent than training under normoxic conditions.
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PMID:Skeletal muscle adaptations to training under normobaric hypoxic versus normoxic conditions. 904 29

Muscle glycogen concentrations in underfed (HYPO) and refed rats (RE) in an earlier study did not correlate with fatigue. We hypothesized that underfeeding slowed glycolysis in the slow-twitch soleus, but not in the fast-twitch extensor digitorum longus (EDL). Thirty adult male Wistar rats were randomly assigned to receive one of two isovolemic and micronutrient-complete liquid diets, a control (CN) energy-complete diet for 10 d or a diet 80% lower in energy (HYPO) for 7 d producing a 20% loss of initial weight. Rats were refed an energy-complete diet for 1 or 4 d (RE1, RE4). Rats were then anesthetized, and the soleus and EDL muscles of the hindlimbs were isolated and electrically stimulated in situ. The pre- and postfatigued muscles were freeze-clamped, lyophilized and stored at -70 degreesC until assayed for specific glycolytic and Krebs cycle metabolites. The HYPO diet caused significantly slower glycolysis in the stimulated soleus but not the EDL compared with the CN diet as supported by the following: 1) a lower fructose-1,6-bisphosphate (F-1,6-P2)/fructose-6-phosphate (F-6-P) ratio; 2) a greater glucose-6-phosphate (G-6-P)/lactate ratio; 3) a lower lactate/glycogen ratio; and 4) lower lactate concentration. Four days of refeeding normalized the F-1,6-P2/F-6-P ratio, but did not improve the lactate/glycogen or the G-6-P/lactate ratios. We conclude that undernutrition compromises glycolysis only in slow-twitch muscles and that 4 d of refeeding restores phosphofructokinase activity.
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PMID:Feeding a low energy diet and refeeding a control diet affect glycolysis differently in the slow- and fast-twitch muscles of adult male Wistar rats. 977 42

The effect of the distribution of rest periods on the efficacy of interval sprint training is analysed. Ten male subjects, divided at random into two groups, performed distinct incremental sprint training protocols, in which the muscle load was the same (14 sessions), but the distribution of rest periods was varied. The 'short programme' group (SP) trained every day for 2 weeks, while the 'long programme' group (LP) trained over a 6-week period with a 2-day rest period following each training session. The volunteers performed a 30-s supramaximal cycling test on a cycle ergometer before and after training. Muscle biopsies were obtained from the vastus lateralis before and after each test to examine metabolites and enzyme activities. Both training programmes led to a marked increase (all significant, P < 0.05) in enzymatic activities related to glycolysis (phosphofructokinase - SP 107%, LP 68% and aldolase - SP 46%, LP 28%) and aerobic metabolism (citrate synthase - SP 38%, LP 28.4% and 3-hydroxyacyl-CoA dehydrogenase - SP 60%, LP 38.7%). However, the activity of creatine kinase (44%), pyruvate kinase (35%) and lactate dehydrogenase (45%) rose significantly (P < 0.05) only in SP. At the end of the training programme, SP had suffered a significant decrease in anaerobic ATP consumption per gram muscle (P < 0.05) and glycogen degradation (P < 0.05) during the post-training test, and failed to improve performance. In contrast, LP showed a marked improvement in performance (P < 0.05) although without a significant increase in anaerobic ATP consumption, glycolysis or glycogenolysis rate. These results indicate that high-intensity cycling training in 14 sessions improves enzyme activities of anaerobic and aerobic metabolism. These changes are affected by the distribution of rest periods, hence shorter rest periods produce larger increase in pyruvate kinase, creatine kinase and lactate dehydrogenase. However, performance did not improve in a short training programme that did not include days for recovery, which suggests that muscle fibres suffer fatigue or injury.
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PMID:The distribution of rest periods affects performance and adaptations of energy metabolism induced by high-intensity training in human muscle. 1084 46

To investigate the efficacy of the ingestion of vinegar in aiding recovery from fatigue, we examined the effect of dietary acetic acid, the main component of vinegar, on glycogen repletion in rats. Rats were allowed access to a commercial diet twice daily for 6 d. After 15 h of food deprivation, they were either killed immediately or given 2 g of a diet containing 0 (control), 0.1, 0.2 or 0.4 g acetic acid/100 g diet for 2 h. The 0.2 g acetic acid group had significantly greater liver and gastrocnemius muscle glycogen concentration than the control group (P < 0.05). The concentrations of citrate in this group in both the liver and skeletal muscles were >1.3-fold greater than in the control group (P > 0.1). In liver, the concentration of xylulose-5-phosphate in the control group was significantly higher than in the 0.2 and 0.4 g acetic acid groups (P < 0.01). In gastrocnemius muscle, the concentration of glucose-6-phosphate in the control group was significantly lower and the ratio of fructose-1,6-bisphosphate/fructose-6-phosphate was significantly higher than in the 0.2 g acetic acid group (P < 0.05). This ratio in the soleus muscle of the acetic acid fed groups was <0.8-fold that of the control group (P > 0.1). In liver, acetic acid may activate gluconeogenesis and inactivate glycolysis through inactivation of fructose-2,6-bisphosphate synthesis due to suppression of xylulose-5-phosphate accumulation. In skeletal muscle, acetic acid may inhibit glycolysis by suppression of phosphofructokinase-1 activity. We conclude that a diet containing acetic acid may enhance glycogen repletion in liver and skeletal muscle.
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PMID:Acetic acid feeding enhances glycogen repletion in liver and skeletal muscle of rats. 1143 16

Glycolytic flux in white muscle can be increased several-hundredfold by exercise. Phosphofructokinase (PFK; EC 2.7.1.11) is a key regulatory enzyme of glycolysis, but how its activity in muscle is controlled is not fully understood. In order not to neglect integrative aspects of metabolic regulation, we have studied in frogs (Rana temporaria) a physiological form of muscle work (swimming) that can be triggered like a reflex. We analysed swimming to fatigue in well rested frogs, recovery from exercise, and repeated exercise after 2 h of recovery. At various times, gastrocnemius muscles were tested for glycolytic intermediates and effectors of PFK. All metabolites responded similarly to the two periods of exercise, with the notable exception of fructose 2,6-bisphosphate (F2,6P(2)), which we proved to be a most potent activator of frog muscle PFK. The first bout of exercise triggered a more than 10-fold increase in F2,6P(2); PFK activity and the content of F2,6P(2) in muscle were well correlated. F2,6P(2) decreased to pre-exercise levels in fatigued frogs and it virtually disappeared during recovery. Varying by a factor of 70, F2,6P(2) was the most dynamic of all metabolites in muscle. Even more surprisingly, F2,6P(2) did not respond at all to a second bout of exercise. Other activators of PFK, such as Pi, AMP and ADP, are increased as a consequence of increased ATP turnover in contracting muscle cells. This does not apply to F2,6P(2) which is likely to respond to extracellular signals and could be involved in mechanisms by which muscle metabolism is integrated into the metabolism of the whole body. Whether this phenomenon exists in vertebrates other than the frog, and maybe even in humans, and how the content of F2,6P(2)in muscle is controlled are intriguing open questions.
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PMID:Different modes of activating phosphofructokinase, a key regulatory enzyme of glycolysis, in working vertebrate muscle. 1202 62


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