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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent investigations from our and other laboratories indicate that glycogen is a carbon-chain precursor in muscle for the synthesis of TCA cycle intermediates and glutamine. During intense exercise and in conditions of a relative lack of energy (hypoxia, trauma, sepsis) the metabolism of branched-chain amino acids (BCAA) is accelerated in muscle. In the primary BCAA aminotransferase reaction 2-oxoglutarate is used as amino-group acceptor (putting a carbon-drain on the TCA cycle) under formation of glutamate. Glutamate will subsequently react with ammonia, generated in the AMP deaminase reaction or by deamination of amino acids, under formation of glutamine in a reaction catalysed by glutamine synthetase (glutamate + ammonia + ATP--> glutamine + ADP). Muscle glycogen stores may be smaller or less available at high altitude. It is hypothesized that this will lead to premature fatigue (due to both a lack of fuel and of TCA cycle carbon-precursor) and to a reduction in the synthesis rate of glutamine. A chronic reduction in the synthesis rate of glutamine during a long term stay at high altitude on its turn may lead to gut atrophy, bacterial translocation, endotoxemia, muscle protein catabolism and a weakened immune status.
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PMID:Amino acid metabolism, muscular fatigue and muscle wasting. Speculations on adaptations at high altitude. 148 45

The relationship between elevated plasma ammonia (NH3) levels, fatigue development and muscle metabolism were examined in horses during a submaximal fatigue test. Eight Quarter Horse mares were intravenously infused prior to exercise with either sodium acetate (control) or ammonium acetate (AMINF), and exercised to fatigue on an 11% grade treadmill, carrying 27 kg of lead. Time to fatigue was not different (P greater than 0.05) between groups. Intramuscular NH3 and lactate increased (P less than 0.001) during exercise; however, the treatment did not (P greater than 0.05) affect either. A treatment by exercise interaction (P less than 0.01) occurred for plasma NH3. The reciprocal relationship between changes in plasma and intramuscular alanine (ala) and glutamate (glu) indicated activation of the glucose-alanine cycle. Plasma glutamine (gln) increased (P less than 0.001) during exercise; however intramuscular gln was not (P greater than 0.05) altered. The excretion of urea-N was depressed as a result of exercise while the orotic acid/creatinine ratio did not (P greater than 0.05) change. The amino acids and urinary metabolites were not (P greater than 0.05) affected by treatment. These results did not show any metabolic evidence for a role of increased plasma NH3 levels in fatigue development. However this study did provide insight into other aspects of nitrogen metabolism during exercise in the horse.
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PMID:Metabolic responses to ammonium acetate infusion in exercising horses. 168 73

The sublethal biochemical effects of pentachlorophenol (PCP) were investigated in live, intact red abalones (Haliotis rufescens), using a flow-through exposure system, by in vivo 31P NMR spectroscopy. Based on rangefinding tests (6-hr LC50 = 1.6 mg/L; 6-hr no-observable-effect-level (NOEL) = 0.8 mg/L), three abalones were separately exposed to a sublethal concentration (1.2 mg/L) for 5 hr, followed by a 13 hr recovery period. Effects in foot muscle included both a decrease in phosphoarginine and an increase in inorganic monophosphate concentrations ([PA] and [Pi], respectively); both foot muscle concentrations of adenosine triphosphate [ATP] and intracellular pH (pHi) also declined. Parallel in vitro experiments revealed that concentrations of glycerol 3-phosphate, lactate, citrate, succinate, malate, and alanine (Ala) all increased, while those of glyceraldehyde 3-phosphate and glutamine (Gln) remained stable. Also, these effects were not evident until 2 hr into exposure, possibly the time required for PCP to attain an effective concentration in foot muscle. During recovery, while Pi declined to pre-exposure levels, [PA] completely recovered in only one individual. Also, realkalinization of pHi was similar to recovery of [Pi], and ATP returned to near-initial levels, as did glycerol 3-phosphate, lactate, succinate, malate, and Ala; glyceraldehyde 3-phosphate, citrate, and Gln levels declined. Recovery responses corresponded to the time for PCP clearance from foot muscle. The effects of PCP were similar to those of hypoxia, fatigue, hypersalinity, and arginine kinase inhibitors, and so sublethal PCP concentrations may also inhibit electron transport and arginine kinase as well as uncouple mitochondrial oxidative phosphorylation in intact molluscs. Thus, the effects of pollutants on key biochemical processes may now be measured in intact aquatic organisms as they occur, improving our ability to accurately assess the environmental effects of pollutants in the laboratory.
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PMID:Sublethal effects of pentachlorophenol in the abalone (Haliotis rufescens) as measured by in vivo 31P NMR spectroscopy. 188 Jul 88

The present paper reviews evidence for the role of specific amino acids in the etiology of fatigue and the overtraining syndrome in athletes. An increase in the plasma concentration ratio of free tryptophan: branched-chain amino acids may mediate an increase in 5-HT synthesis in the brain and thus induce fatigue during exercise. Glutamine is essential for the proper functioning of cells of the immune system and a decrease in plasma glutamine concentration post-exercise and in overtraining may induce an impairment in immune function. Branched-chain amino acids may play a central role in both these processes. Thus, they compete with free tryptophan for entry into the brain. Branched-chain amino acids may also be important precursors of nitrogen for the synthesis of glutamine in skeletal muscle or important in the control of glutamine release from muscle. Consequently, the metabolism of glutamine, tryptophan, and branched-chain amino acids may be the key to understanding some aspects of central fatigue and some aspects of immunosuppression that are very relevant to athletic endeavor. They may be also relevant to other physiological and pathological conditions.
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PMID:A communicational link between skeletal muscle, brain, and cells of the immune system. 219 90

The changes in ammonia (NH3) and amino acid contents in human skeletal muscle during isometric exercise (2/3 maximal voluntary contraction force) to fatigue have been investigated. Biopsies from musculus quadriceps femoris were obtained at rest, fatigue, and 1 and 4 min recovery. Muscle NH3 (n = 9) increased from 1.3 +/- 0.3 (mean +/- SE) mmol/kg dry muscle (dm) at rest to 3.6 +/- 0.6 at fatigue (P less than 0.01) and remained elevated during recovery, whereas the lactate increase after contraction decreased rapidly during recovery. Total adenine nucleotide (TAN) content decreased from 28.7 +/- 0.5 mmol/kg dm at rest to 25.1 +/- 0.6 at fatigue (P less than 0.001). Muscle glutamine did not change after contraction (P greater than 0.05), whereas glutamate decreased (P less than 0.001), and alanine increased (P less than 0.001). In vivo AMP deaminase activity (measured by the rate of TAN decrease) was positively correlated with the percentage of fast-twitch fibers (r = 0.92; P less than 0.001) and the ATP turnover rate (r = 0.75; P less than 0.001) but was not related to the muscle lactate content (r = 0.27; P greater than 0.05). Phosphocreatine decreased to 6.1 +/- 0.7 mmol/kg dm (range = 1-11) after contraction. It is concluded that during exercise activation of AMP deaminase in vivo occurs when a high ATP turnover rate is coupled with a low phosphocreatine level, muscle pH is of minor importance for direct activation of AMP deaminase in vivo, and increases in NH3 do not have an important influence on glycolysis.
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PMID:Muscle ammonia metabolism during isometric contraction in humans. 287 18

Hepatocytes from rats deprived of food for 48 h synthesized glucose and urea from glutamine at a rate which, at pH 7.3, was markedly stimulated (175-250%) by dibutyryl cAMP, phenylephrine, and norepinephrine, in agreement with previous investigators. These effectors also stimulated respiration, elevating ATP production by the amount required for the increase in glucose and urea synthesis. Both the basal and stimulated rates were strongly pH dependent with maxima in the region of pH 7.2-7.6 (urea synthesis) and 7.2-7.5 (glucose synthesis) and declined rapidly on either side of these pH values. The inhibitions at acid and alkaline pH were neither due to lack of energy nor to limitation in glutamine uptake. The intracellular concentrations of aspartate, glutamate, and glutamine were lower at pH 6.7 than at pH 7.3 and were differently affected by dibutyryl cAMP and phenylephrine at the two pH values investigated. When calcium was omitted from the suspending medium, the basal rates of glucose and urea production were decreased as was stimulation by the effectors, phenylephrine completely, and the others partially. The stimulations by phenylephrine and dibutyryl cAMP were additive under all conditions tested. The pattern of metabolite changes indicates that although both effectors stimulated glutaminase and increased supply of aspartate to the argininosuccinate synthetase, dibutyryl cAMP gave greater activation of glutaminase whereas the adrenergic agonists gave greater stimulation of later steps on the biosynthetic pathways. It may be physiologically important than at acid pH both ureagenesis and gluconeogenesis are severely suppressed and cannot be effectively stimulated by the major hormonal regulators of these pathways.
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PMID:pH dependence of hormonal regulation of gluconeogenesis and urea synthesis from glutamine in suspensions of hepatocytes. 298 Dec 10

The effect of dynamic exercise on muscle and blood ammonia (NH3) and amino acid contents has been investigated. Eight healthy men cycled at 50% and 97% of maximal oxygen uptake for 10 min and 5.2 min (to fatigue), respectively. Biopsies (quadriceps femoris muscle), arterial and femoral venous blood samples were obtained at rest and during exercise. Muscle NH3 at rest and after submaximal exercise was (means +/- SE) 0.5 +/- 0.1 mmol/kg dry muscle (d.m.) and increased to 4.1 +/- 0.5 mmol/kg d.m. at fatigue (P less than 0.001). The total adenine nucleotide (TAN) pool (TAN = ATP + ADP + AMP) did not change after submaximal exercise but decreased significantly at fatigue (P less than 0.001). The decrease in TAN was similar to the increase in NH3. Muscle lactate was 3 +/- 1 mmol/kg d.m. at rest and increased to 104 +/- 5 mmol/kg d.m. at fatigue. Whole blood and plasma NH3 did not change significantly during submaximal but both increased significantly during maximal exercise (P less than 0.001). During maximal exercise the leg released 7,120 mumol/min of lactate, whereas only 89 mumol/min of NH3 were released. NH3 accumulation in muscle could buffer only 3% of the hydrogen ions released from lactate, and NH3 release could account for only 1% of the net hydrogen ion transport out of the cell. Muscle glutamine was constant throughout the study, whereas glutamate decreased and alanine increased during exercise (P less than 0.001). No significant changes in either arterial whole blood glutamine or glutamate were observed. Arterial plasma glutamine and glutamate concentrations, however, increased and decreased (P less than 0.001), respectively, during exercise. It is concluded that (1) muscle and blood NH3 levels increase only during strenuous exercise and (2) NH3 accumulation is of minor importance for regulating acid-base balance in body fluids during exercise.
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PMID:Muscle ammonia and amino acid metabolism during dynamic exercise in man. 374 56

Hypocaloric dieting and fasting alter the contraction-relaxation characteristics of skeletal muscle and result in low frequency fatigue. We report the metabolic and structural changes in skeletal muscle in five morbidly obese female subjects who had biopsies of the gastrocnemius muscle on a base-line diet (2500 kcal/day) followed by a repeat biopsy after 2 wk of a 400-kcal/day carbohydrate diet. Hypocaloric dieting resulted in a significant increase in the intracellular muscle calcium content (p less than 0.05), which may account for the observed changes in muscle function. There were no significant changes in muscle glycogen, lactate, pyruvate, or free energy stores. There was a significant decrease in muscle enzymes [phosphofructokinase (p less than 0.05), succinate dehydrogenase (p less than 0.02)] and some muscle amino acid levels [glutamine (p less than 0.025), glycine (p less than 0.01), and alanine (p less than 0.02)], while muscle histochemistry showed type II fiber atrophy (p less than 0.025). However, these changes reflect a generalized response to hypocaloric dieting and probably do not explain the specific functional changes. Change in the muscle calcium content is probably an important mediator of the adverse functional effects of malnutrition.
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PMID:Metabolic and structural changes in skeletal muscle during hypocaloric dieting. 620 Oct 62

Synaptic glutamate release involves the accumulation of cytoplasmic glutamate in synaptic vesicles, whereafter it is released by triggered exocytosis. As glutamatergic terminals are known to be functionally diverse it was of interest to examine whether the presynaptic glutamate supply differs between individual axon terminals with distinct release properties. The glutamatergic terminals in the crustacean neuromuscular system system comprise a "phasic" type which shows fatigue of release during repetitive stimulation, and a "tonic" type which can maintain transmission for long periods. Quantitative immunogold analysis showed that the axons in a tonic nerve innervating slow muscles in the abdomen contained two times higher levels of glutamate labeling over axoplasmic matrix and over mitochondria, as compared to the corresponding elements in a phasic nerve. Similar results were obtained when adjacent phasic and tonic axons in a mixed nerve innervating leg muscles were compared. In the terminal regions of tonic and phasic axons the glutamate labeling differed correspondingly over axoplasmic matrix and mitochondria, while the synaptic vesicles showed a similar strong accumulation of labeling in both types of terminal. The level of labeling for glutamine, a glutamate precursor, was closely similar in phasic and tonic axons. The axoplasmic glutamate concentration was estimated to be in the low millimolar range, through comparison with coprocessed conjugates with known glutamate concentration. These results show that fatigue-resistant tonic axons and terminals contain higher levels of glutamate than fatiguable phasic axons, presumably representing an adaptation to the markedly different impulse activities in the two types of neuron. The axonal glutamate concentrations are in the range of the Km value for vesicular glutamate transport. Thus in tonic axons the high glutamate level appears to promote an efficient refilling of synaptic vesicles during sustained release, while in phasic axons the refilling should be slower which is compatible with an infrequent release.
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PMID:Presynaptic glutamate levels in tonic and phasic motor axons correlate with properties of synaptic release. 747 71

To help clarify the overtraining syndrome (OTS), a combination of parameters were measured in ten athletes who were suffering from OTS. Blood samples were obtained at rest and a range of haematological, biochemical and immunological tests were carried out on the samples. For each parameter, the mean value for the group was compared to an established normal range amongst age-matched controls. The subjects were also asked to complete a questionnaire to establish the severity of their condition. The data indicated that the debilitating fatigue experienced by the OTS sufferers was not related to any of the blood parameters traditionally associated with chronic exercise stress, since levels were normal in OTS. The only parameter measured which deviated significantly from the normal range for both the sedentary controls and the athletes was the plasma concentration of glutamine. Although the data in this study would suggest that plasma glutamine concentrations represented an objective, measurable difference between OTS subjects and normal controls, it remains to be shown that there is any correlation between glutamine concentrations and other clinical symptoms of OTS such as physical capability.
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PMID:The haematological, biochemical and immunological profile of athletes suffering from the overtraining syndrome. 755 22


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