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

The effect of prior glycogen depletion on glycolysis [flux through phosphofructokinase (PFK)] and inosine monophosphate (IMP) formation in human skeletal muscle has been investigated. Eight subjects cycled at a work load calculated to elicit 95% of maximal O2 uptake on two occasions, the first to fatigue [5.5 +/- 0.3 (SE) min] and the second at the same workload and for the same duration as the first. Before the first experiment, muscle glycogen stores were lowered by a combination of exercise and diet. Before the second experiment, muscle glycogen stores were supercompensated. In the low-glycogen (LG) state muscle glycogen decreased from 201 +/- 31 mmol glucosyl units/kg dry wt at rest to 105 +/- 28 after exercise, and in the high-glycogen (HG) state from 583 +/- 40 to 460 +/- 49. The accumulation of fructose 6-phosphate (F-6-P; activator of PFK) during exercise was markedly attenuated in the LG state (P less than 0.01), whereas lactate accumulation in muscle was similar between treatments, suggesting that muscle pH was also similar. Glycolysis (estimated from glycogenolysis minus accumulation of hexose monophosphates) was not measurably different between treatments (LG = 88 +/- 17, HG = 106 +/- 43 mmol/kg dry wt; P greater than 0.05). IMP was significantly greater in the LG state after exercise (3.63 +/- 0.85 vs. 1.97 +/- 0.44 mmol/kg dry wt; P less than 0.05). It is concluded that decreased glycogen availability does not measurably alter the rate of muscle glycolysis during intense exercise. It is hypothesized that the attenuated increase in F-6-P in the LG state, which should theoretically decrease glycolysis, is compensated for by increases in free ADP and AMP (activators of PFK) at the enzymatic site during the contraction phase. The greater increase in IMP in the LG state is consistent with this hypothesis, since ADP and AMP are also activators of AMP deaminase.
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PMID:Role of glycogen in control of glycolysis and IMP formation in human muscle during exercise. 205 62

Two patients with muscle phosphorylase deficiency [McArdle's disease (McA)] were studied during bicycle exercise at 40 (n = 2) and 60 W (n = 1). Peak heart rate was 170 and 162 beats/min, corresponding to approximately 90% of estimated maximal heart rate. Muscle samples were taken at rest and immediately after exercise from the quadriceps femoris. Lactate content remained low in both muscle and blood. Acetylcarnitine, which constitutes a readily available form of acetyl units and thus a substrate for the tricarboxylic acid cycle, was very low in McA patients both at rest and during exercise, corresponding to approximately 17 and 11%, respectively, of that in healthy subjects. Muscle NADH was unchanged during exercise in McA patients in contrast to healthy subjects, in whom NADH increases markedly at high exercise intensities. Despite low lactate levels, arterial plasma NH3 and muscle inosine 5'-monophosphate increased more steeply relative to work load in McA patients than in healthy subjects. The low postexercise levels of lactate, acetylcarnitine, and NADH in McA patients support the idea that exercise performance is limited by the availability of oxidative fuels. Increases in muscle inosine 5'-monophosphate and plasma NH3 indicate that lack of glycogen as an oxidative fuel is associated with adenine nucleotide breakdown and increased deamination of AMP. It is suggested that the early onset of fatigue in McA patients is caused by an insufficient rate of ADP phosphorylation, resulting in transient increases in ADP.
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PMID:Impaired oxidative metabolism increases adenine nucleotide breakdown in McArdle's disease. 226 40

Ketogenic capacity of mitochondria from the remnant liver of 70% hepatectomized rats was studied in relation to mitochondrial phosphorylative activity. Ketogenic capacity increased to a maximum of 6.04 +/- 0.39 from 3.84 +/- 0.13 of control, with an enhancement of mitochondrial phosphorylative activity 6 hr after hepatectomy, and then decreased to normal levels within 24 hr. Adenylate energy charge, (ATP + 1/2ADP)/(ATP + ADP + AMP), of the remnant liver decreased to 0.825 +/- 0.006 as compared to 0.849 +/- 0.002 of control 6 hr after operation. At 12 hr, total ketone body concentrations of the arterial blood increased concomitant with a fall in ketone body ratio (acetoacetate/3-hydroxybutyrate) which reflects the decreased liver mitochondrial redox (NAD+/NADH) state. These findings suggest that an enhancement of mitochondrial fatty acid oxidation and ketogenesis occurs concomitant with an enhancement of mitochondrial phosphorylative activity in the remnant liver in response to a decreased energy charge after 70% hepatectomy.
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PMID:Biological significance of enhanced mitochondrial ketogenesis during the early stages after 70% hepatectomy in rats. 229 82

A common finding in oxidant-induced organ injury is loss of vascular endothelial cell (EC) integrity and subsequent leak. The mechanisms involved are unclear, but maintenance of EC structure and functional integrity is highly dependent on the EC energy level. This study investigates whether oxidant-induced EC injury and concomitant increased monolayer permeability correlate with decreased energy levels. Rabbit pulmonary microvascular EC in vitro were exposed to varying levels of glucose oxidase as an oxidant-generating source for 2 h. Permeability changes were determined by albumin-Evans blue dye exclusion by monolayers of EC. ATP (nm/10(6) cells) and energy charge [ATP + 1/2ADP/(ATP + ADP + AMP)] were determined by HPLC. ATP and energy charge were found to decrease as permeability increased in response to increasing glucose oxidase concentration. ATP levels were a significantly more sensitive predictor of increased permeability than was energy charge. At 24 h, both permeability and ATP levels returned toward baseline. It appears that cell energy charge is preserved despite significant increases in monolayer permeability.
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PMID:Oxidant-induced endothelial leak correlates with decreased cellular energy levels. 229 71

The predominant route for adenine nucleotide catabolism in skeletal muscle is deamination of AMP to inosine monophosphate (IMP) and ammonia (NH3). Deamination of AMP is enhanced during exercise when the capacity to rephosphorylate ADP is impaired. Thus, in human muscle the formation of IMP (NH3) during exercise is augmented under the following conditions (1) at high intensities, (2) during beta-adrenoceptor blockade, (3) during hypoxia, (4) after detraining, and (5) at low glycogen levels. The formation of IMP is related to the metabolic stress (as indicated by the degree of phosphocreatine breakdown and lactate accumulation), the rate of ATP turnover, and the fiber type composition. During maximal exercise at 100% of VO2max or sustained isometric contractions to fatigue, about 15% of the adenine nucleotide (AN) pool is degraded through deamination of AMP to IMP. It is suggested that the stimulus for increased AMP deamination is increased transient levels of ADP and AMP in the contracting muscle fiber. Deamination of AMP to IMP and NH3 provides a sink for ADP, whereby the ATP/ADP ratio and the phosphorylation potential are kept high, which may be essential for the continuation of the contraction process. This implies that the relative levels of the adenine nucleotides are more important for maintenance of adequate cellular function than the absolute concentration of ATP.
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PMID:Adenine nucleotide depletion in human muscle during exercise: causality and significance of AMP deamination. 236 81

The protective effect of calcium antagonists on ischemic heart has been attributed to decreased energy expenditure. We administered one of the newer calcium antagonists, DL-bepridil (0.1-10 microM), to Langendorff rat hearts 10 or 15 min before ischemia (flow reduction approximately 80%). Vasodilation during normoxia was already observed with 0.3 microM DL-bepridil (flow increase 34%, p less than 0.005). This concentration decreased normoxic contractility and ischemic purine release, a marker for ATP breakdown. In the absence of bepridil, purine release of hearts that were made ischemic was 8.5-fold higher than that of normoxic control hearts. With 1 microM bepridil, the ischemic purine efflux was suppressed by 55% (p less than 0.05), with negative inotropy (p greater than 0.05) during normoxia. At 3 and 10 microM, bepridil decreased normoxic contractility by 40 and 75%, respectively (p less than 0.001), concomitant with a decrease in ischemic purine release by 80 and 76%, respectively (p less than 0.01). At the end of ischemia, myocardial ATP and creatine phosphate had decreased by 22 and 55%, respectively (p less than 0.05), and ADP, AMP, and creatine had increased 1.5-3.5-fold (p less than 0.05). Bepridil (3 microM) normalized the adenine nucleotide values; creatine and creatine phosphate approached control levels. The dose-dependent protection of the ischemic heart by bepridil appears to arise from its negative inotropic action during normoxia.
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PMID:Protection by bepridil against myocardial ATP-catabolism is probably due to negative inotropy. 244 Nov 54

By the use of invasive techniques, skeletal muscle has been shown to contribute to thermogenesis induced by glucose in humans. In an attempt to study this phenomenon by a non-invasive method, this study investigated intracellular high-energy phosphorous compounds in calf muscle by 31P MR spectroscopy during an oral glucose load in healthy lean subjects. The inorganic phosphate concentration increased gradually (P less than 0.05) after glucose intake. The phosphocreatine/inorganic phosphate rate decreased (P less than 0.05) and the estimated ADP concentration increased. ATP and intracellular pH remained unchanged after the glucose administration. No changes were seen in the control experiments. The processes responsible for the decreased energy state of the skeletal muscle cell may be an obligatory conversion of glucose to glycogen. Also, facultative processes, such as sodium/potassium pumping and substrate cycles stimulated by the sympatho-adrenal system, may be partly responsible.
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PMID:Changes of high-energy phosphorous compounds in skeletal muscle during glucose-induced thermogenesis in man. A 31P MR spectroscopy study. 259 28

1. Maximal calcium-activated force (Fmax) and calcium sensitivity were markedly decreased in detergent-skinned fibres from skeletal and cardiac muscle by solutions that mimicked the total milieu changes associated with fatigue and hypoxia. Further experiments determined the relative contribution of each of the individual changes in milieu. 2. Both Ca2+ sensitivity and Fmax of skeletal and cardiac fibres were decreased with increased [H+] or inorganic phosphate (Pi). These effects were greater in cardiac muscle. 3. Decreasing MgATP over the range observed with fatigue and hypoxia (6.8-4.7 mM) had no effect on Fmax or Ca2+ sensitivity of either muscle type. 4. Decreasing phosphocreatine (PCr: 15-1 mM) increased Fmax but had little effect on Ca2+ sensitivity in both muscle types. In cardiac fibres, the effect on Fmax could be mimicked by inhibition of endogenous creatine kinase. 5. ADP (0.7 mM) increased Fmax and Ca2+ sensitivity, while AMP (0.06 mM) slightly increased Fmax but had no effect on Ca2+ sensitivity of either skeletal or cardiac fibres. 6. Creatine (25 mM) had no significant effect on either Ca2+ sensitivity or Fmax of skeletal and cardiac muscle fibres. At higher levels (50 mM), however, creatine depressed Fmax and slightly altered Ca2+ sensitivity. 7. Thiophosphorylation of myosin P light chains (phosphorylatable light chains of myosin) in rabbit psoas fibres had no effect on Ca2+ sensitivity, yet slightly but significantly increased Fmax under fatigue conditions. 8. Reducing the affinity for ATP hydrolysis (by adding ADP, AMP and creatine) over the range calculated for fatigue/hypoxia (60-45 kJ/mol) produced the enhancement in Fmax expected from added ADP and AMP in cardiac but not skeletal muscle, indicating that changes in affinity influence Fmax of skeletal muscle. Reducing affinity produced little change in Ca2+ sensitivity of skeletal muscle. In contrast, the change produced in cardiac muscle was greater than that expected from addition of ADP and AMP; i.e. decreasing affinity increases calcium sensitivity of the heart. 9. Simple summation of all significant changes expected from each constituent altered by fatigue/hypoxia adequately predicted the observed changes in Fmax and Ca2+ sensitivity in both cardiac and skeletal muscle fibres with but one exception (the change in Ca2+ sensitivity of skeletal muscle at pH 7 was slightly overestimated).
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PMID:Changes of intracellular milieu with fatigue or hypoxia depress contraction of skinned rabbit skeletal and cardiac muscle. 260 Aug 30

Eight healthy men cycled at a work load corresponding to approximately 70% of maximal O2 uptake (VO2max) to fatigue (exercise I). Exercise to fatigue at the same work load was repeated after 75 min of rest (exercise II). Exercise duration averaged 65 and 21 min for exercise I and II, respectively. Muscle (quadriceps femoris) content of glycogen decreased from 492 +/- 27 to 92 +/- 20 (SE) mmol/kg dry wt and from 148 +/- 17 to 56 +/- 17 (SE) mmol/kg dry wt during exercise I and II, respectively. Muscle and blood lactate were only moderately increased during exercise. The total adenine nucleotide pool (TAN = ATP + ADP + AMP) decreased and inosine 5'-monophosphate (IMP) increased in the working muscle during both exercise I (P less than 0.001) and II (P less than 0.01). Muscle content of ammonia (NH3) increased four- and eight-fold during exercise I and II, respectively. The working legs released NH3, and plasma NH3 increased progressively during exercise. The release of NH3 at the end of exercise II was fivefold higher than that at the same time point in exercise I (P less than 0.001, exercise I vs. II). It is concluded that submaximal exercise to fatigue results in a breakdown of the TAN in the working muscle through deamination of AMP to IMP and NH3. The relatively low lactate levels demonstrate that acidosis is not a necessary prerequisite for activation of AMP deaminase. It is suggested that the higher average rate of AMP deamination during exercise II vs. exercise I is due to a relative impairment of ATP resynthesis caused by the low muscle glycogen level.
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PMID:Adenine nucleotide degradation in human skeletal muscle during prolonged exercise. 275 35

To investigate the hypothesis that the rate of fatigue development is not influenced by the absolute duration of contraction (train duration) and relaxation (off-phase of duty cycle) at constant duty cycle, strips of the diaphragm from 36 male adult rats (mean +/- SD wt 152 +/- 21 g) were stimulated directly for periods of 180, 250, and 320 ms at a constant duty cycle of 50%. The frequency of stimulation was adjusted to produce 40% of maximal tetanic tension at supramaximal voltages. After 30 min of stimulation, analysis of twitch characteristics between control and experimental groups indicated a prolongation of contraction time of 9% (P less than 0.05), an increase in relaxation time of 75% (P less than 0.05), and a decrease in twitch tension by 78% (P less than 0.05). Similarly, reductions (P less than 0.05) in isometric force output at high stimulation frequency (100 Hz) of 58% and at low frequency (20 Hz) of 67% were also noted. These changes were accompanied by an approximately 60% reduction in the maximal velocity of shortening. No difference was observed for any of the mechanical measures between experimental conditions. After 30-min stimulation, decreases of between 43 and 46% were noted for ATP (P less than 0.05) and increases of between three- and fourfold noted for IMP (P less than 0.05). No changes were found for either ADP or AMP. Total adenine nucleotide concentrations declined (P less than 0.05) an average of 24%. As with the mechanical data, no differences were found between the different stimulation conditions. It is concluded that for the conditions studied, fatigue mechanisms become manifest early in the stimulation period and are only minimally altered by the duration of specific contractions provided the relaxation period is of equal duration.
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PMID:Mechanical and metabolic alterations in rat diaphragm during electrical stimulation. 275 44


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