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Query: UMLS:C0392674 (exhaustion)
 13,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purine nucleotides (ATP, ADP, AMP, IMP), creatine, phosphocreatine, lactate, pyruvate and glycogen were measured in rainbow trout (Oncorhynchus mykiss) white muscle following exercise to exhaustion. Estimates of intracellular pH permitted calculation of free concentrations of nucleotides ([nucleotide]f) required for most models of control of energy metabolism. Creatine charge, [PCr]/([PCr]+[Cr]), fell from 0.49 +/- 0.05 (mean +/- S.E.M.) to 0.08 +/- 0.02 with exercise but recovered completely by the first sample (2 h). Although [ATP] declined to 24% of resting levels and recovered very slowly, RATP, [ATP]/([ATP]+[ADP]f+[AMP]f), and energy charge, EC, ([ATP]+0.5[ADP]f)/([ATP]+[ADP]f+[AMP]f), recovered as quickly as creatine charge. Changes in [IMP] mirrored those in [ATP], suggesting that AMP deaminase is responsible for maintaining RATP and EC. Recovery of carbon status was much slower than recovery of energy status. Lactate increased from 4 mumol g-1 at rest to 40 mumol g-1 at exhaustion and did not recover for more than 8 h. Glycogen depletion and resynthesis followed a similar time course. During the early stages of recovery, calculated [ADP]f declined by more than 10-fold relative to the resting values. The resulting high [ATP]/[ADP]f ratios may limit the rate at which white muscle mitochondria can produce ATP to fuel glycogenesis in situ. It is postulated that the high [ATP]/[ADP]f ratios are required to drive pyruvate kinase in the reverse direction for glyconeogenesis in recovery.
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PMID:Integrating metabolic pathways in post-exercise recovery of white muscle. 160 73

The purpose of this investigation was to examine the role of intermediary metabolism in the maintenance of proton and charge balance in rainbow trout white muscle during exercise. With increasing power outputs, there was a greater reliance on white fibers and anaerobic processes for energy production. Glycogen content declined from a pre-exercise (pre-ex) level of 23 to less than 1 mumol/g following the exhaustive swim, with its greatest rate of decline occurring during the burst swim. Lactate accumulation reached a maximum of 43 mumol/g during the exhaustive swim. PCr declined from about 20 to less than 2 mumol/g at exhaustion with a concomitant accumulation of Cr. ATP decreased from about 7.3 to 2.7 mumol/g while inorganic phosphate and IMP increased to about 56 and 4.3 mumol/g, respectively. The intramuscular pH fell from 6.97 to 6.93 during the sustained swim, declining further to 6.65 during the burst swim and reaching a minimum of 6.56 at exhaustion. Exercise induced depletions of high energy compounds and accumulations of metabolic end products nearly stabilized the accompanying intracellular perturbations in charge and proton levels. Compensatory shifts in Na+, K+ and Cl- served to negate the residual imbalances such that electrical neutrality, membrane potential and pH were preserved.
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PMID:The role of intermediary metabolism in the maintenance of proton and charge balance during exercise. 282 1

AMP-degrading pathways in Azotobacter vinelandii cells were investigated. AMP nucleosidase (EC 3.2.2.4) was rapidly synthesized and reached a maximum at 24 h, while the activity of 5'-nucleotidase (EC 3.1.3.5) specific for AMP, which was negligible during the logarithmic phase of the growth, first appeared in 24 h-cultures, and reached a maximum after complete exhaustion of sucrose from the growth medium (70 h). Cell-free extracts of A. vinelandii of 48 h-cultures hydrolyzed AMP to ribose 5-phosphate and adenine in the presence of ATP, and adenine was deaminated to hypoxanthine. When ATP was excluded, AMP was dephosphorylated to adenosine, which was further metabolized to inosine, and finally to hypoxanthine. Hypoxanthine thus formed was reutilized for the salvage synthesis of IMP under the conditions where 5-phosphoribosyl 1-pyrophosphate was able to be supplied. These results suggest that the levels of ATP can determine the rate of AMP degradation by the AMP nucleosidase- and 5-'nucleotidase-pathways. The role of ATP in the AMP degradation was discussed in relation to the regulatory properties of AMP nucleosidase, inosine nucleosidase (EC. 3.2.2.2) and adenosine deaminase (EC 3.5.4.4).
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PMID:Adenine nucleotide metabolism in Azotobacter vinelandii. Two metabolic pathways of AMP degradation. 626 50

To examine the effect of ambient temperature on metabolism during fatiguing submaximal exercise, eight men cycled to exhaustion at a workload requiring 70% peak pulmonary oxygen uptake on three separate occasions, at least 1 wk apart. These trials were conducted in ambient temperatures of 3 degrees C (CT), 20 degrees C (NT), and 40 degrees C (HT). Although no differences in muscle or rectal temperature were observed before exercise, both muscle and rectal temperature were higher (P < 0.05) at fatigue in HT compared with CT and NT. Exercise time was longer in CT compared with NT, which, in turn, was longer compared with HT (85 +/- 8 vs. 60 +/- 11 vs. 30 +/- 3 min, respectively; P < 0.05). Plasma epinephrine concentration was not different at rest or at the point of fatigue when the three trials were compared, but concentrations of this hormone were higher (P < 0.05) when HT was compared with NT, which in turn was higher (P < 0.05) compared with CT after 20 min of exercise. Muscle glycogen concentration was not different at rest when the three trials were compared but was higher at fatigue in HT compared with NT and CT, which were not different (299 +/- 33 vs. 153 +/- 27 and 116 +/- 28 mmol/kg dry wt, respectively; P < 0.01). Intramuscular lactate concentration was not different at rest when the three trials were compared but was higher (P < 0.05) at fatigue in HT compared with CT. No differences in the concentration of the total intramuscular adenine nucleotide pool (ATP + ADP + AMP), phosphocreatine, or creatine were observed before or after exercise when the trials were compared. Although intramuscular IMP concentrations were not statistically different before or after exercise when the three trials were compared, there was an exercise-induced increase (P < 0.01) in IMP. These results demonstrate that fatigue during prolonged exercise in hot conditions is not related to carbohydrate availability. Furthermore, the increased endurance in CT compared with NT is probably due to a reduced glycogenolytic rate.
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PMID:Effect of ambient temperature on human skeletal muscle metabolism during fatiguing submaximal exercise. 1006 3

To examine the effect of training status on muscle metabolism during exercise, seven endurance-trained [peak oxygen uptake (VO(2 peak)) = 65.8 +/- 2.4 ml. kg(-1). min(-1)] and six untrained (VO(2 peak) = 46. 2 +/- 1.9 ml. kg(-1). min(-1)) men cycled to fatigue at a work rate calculated to require 70% VO(2 peak). Time to exhaustion was 36% longer (P < 0.01) in trained (TR) compared with untrained (UT) men (148 +/- 11 vs. 95 +/- 8 min). Although intramuscular glycogen content was reduced (P < 0.05) in both TR and UT at fatigue, IMP, a marker of a mismatch between ATP supply and demand, was only elevated (P < 0.01) in UT muscle at fatigue and was approximately fourfold higher at this point in UT compared with TR. These data demonstrate that fatiguing submaximal exercise was associated with a similar low level of intramuscular glycogen in both TR and UT men, but a mismatch between ATP supply and demand only occurred in UT individuals.
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PMID:Muscle IMP accumulation during fatiguing submaximal exercise in endurance trained and untrained men. 1040 85

The effects of sprint training on muscle metabolism and ion regulation during intense exercise remain controversial. We employed a rigorous methodological approach, contrasting these responses during exercise to exhaustion and during identical work before and after training. Seven untrained men undertook 7 wk of sprint training. Subjects cycled to exhaustion at 130% pretraining peak oxygen uptake before (PreExh) and after training (PostExh), as well as performing another posttraining test identical to PreExh (PostMatch). Biopsies were taken at rest and immediately postexercise. After training in PostMatch, muscle and plasma lactate (Lac(-)) and H(+) concentrations, anaerobic ATP production rate, glycogen and ATP degradation, IMP accumulation, and peak plasma K(+) and norepinephrine concentrations were reduced (P<0.05). In PostExh, time to exhaustion was 21% greater than PreExh (P<0.001); however, muscle Lac(-) accumulation was unchanged; muscle H(+) concentration, ATP degradation, IMP accumulation, and anaerobic ATP production rate were reduced; and plasma Lac(-), norepinephrine, and H(+) concentrations were higher (P<0.05). Sprint training resulted in reduced anaerobic ATP generation during intense exercise, suggesting that aerobic metabolism was enhanced, which may allow increased time to fatigue.
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PMID:Skeletal muscle metabolic and ionic adaptations during intense exercise following sprint training in humans. 1105 28

The hypothesis that fatigue during prolonged exercise arises from insufficient intramuscular glycogen, which limits tricarboxylic acid cycle (TCA) activity due to reduced TCA cycle intermediates (TCAI), was tested in this experiment. Seven endurance-trained men cycled at approximately 70% of peak O(2) uptake (Vo(2 peak)) until exhaustion with low (LG) or high (HG) preexercise intramuscular glycogen content. Muscle glycogen content was lower (P < 0.05) at fatigue than at rest in both trials. However, the increase in the sum of four measured TCAI (>70% of the total TCAI pool) from rest to 15 min of exercise was not different between trials, and TCAI content was similar after 103 +/- 15 min of exercise (2.62 +/- 0.31 and 2.59 +/- 0.28 mmol/kg dry wt for LG and HG, respectively), which was the point of volitional fatigue during LG. Subjects cycled for an additional 52 +/- 9 min during HG, and although glycogen was markedly reduced (P < 0.05) during this period, no further change in the TCAI pool was observed, thus demonstrating a clear dissociation between exercise duration and the size of the TCAI pool. Neither the total adenine nucleotide pool (TAN = ATP + ADP + AMP) nor IMP was altered compared with rest in either trial, whereas creatine phosphate levels were not different when values measured at fatigue were compared with those measured after 15 min of exercise. These data demonstrate that altered glycogen availability neither compromises TCAI pool expansion nor affects the TAN pool or creatine phosphate or IMP content during prolonged exercise to fatigue. Therefore, our data do not support the concept that a decrease in muscle TCAI during prolonged exercise in humans compromises aerobic energy provision or is the cause of fatigue.
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PMID:Glycogen availability does not affect the TCA cycle or TAN pools during prolonged, fatiguing exercise. 1501 97

ClC proteins are a family of chloride channels and transporters that are found in a wide variety of prokaryotic and eukaryotic cell types. The mammalian voltage-gated chloride channel ClC-1 is important for controlling the electrical excitability of skeletal muscle. Reduced excitability of muscle cells during metabolic stress can protect cells from metabolic exhaustion and is thought to be a major factor in fatigue. Here we identify a novel mechanism linking excitability to metabolic state by showing that ClC-1 channels are modulated by ATP. The high concentration of ATP in resting muscle effectively inhibits ClC-1 activity by shifting the voltage gating to more positive potentials. ADP and AMP had similar effects to ATP, but IMP had no effect, indicating that the inhibition of ClC-1 would only be relieved under anaerobic conditions such as intense muscle activity or ischemia, when depleted ATP accumulates as IMP. The resulting increase in ClC-1 activity under these conditions would reduce muscle excitability, thus contributing to fatigue. We show further that the modulation by ATP is mediated by cystathionine beta-synthase-related domains in the cytoplasmic C terminus of ClC-1. This defines a function for these domains as gating-modulatory domains sensitive to intracellular ligands, such as nucleotides, a function that is likely to be conserved in other ClC proteins.
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PMID:Cytoplasmic ATP-sensing domains regulate gating of skeletal muscle ClC-1 chloride channels. 1602 67

Chronic hypoxia has been proposed to induce a closer coupling in human skeletal muscle between ATP utilization and production in both lowlanders (LN) acclimatizing to high altitude and high-altitude natives (HAN), linked with an improved match between pyruvate availability and its use in mitochondrial respiration. This should result in less lactate being formed during exercise in spite of the hypoxaemia. To test this hypothesis six LN (22-31 years old) were studied during 15 min warm up followed by an incremental bicycle exercise to exhaustion at sea level, during acute hypoxia and after 2 and 8 weeks at 4100 m above sea level (El Alto, Bolivia). In addition, eight HAN (26-37 years old) were studied with a similar exercise protocol at altitude. The leg net lactate release, and the arterial and muscle lactate concentrations were elevated during the exercise in LN in acute hypoxia and remained at this higher level during the acclimatization period. HAN had similar high values; however, at the moment of exhaustion their muscle lactate, ADP and IMP content and Cr/PCr ratio were higher than in LN. In conclusion, sea-level residents in the course of acclimatization to high altitude did not exhibit a reduced capacity for the active muscle to produce lactate. Thus, the lactate paradox concept could not be demonstrated. High-altitude natives from the Andes actually exhibit a higher anaerobic energy production than lowlanders after 8 weeks of acclimatization reflected by an increased muscle lactate accumulation and enhanced adenine nucleotide breakdown.
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PMID:The lactate paradox revisited in lowlanders during acclimatization to 4100 m and in high-altitude natives. 1913 48

Exercise enhances branched-chain amino acid (BCAA) catabolism, and BCAA supplementation influences exercise metabolism. However, it remains controversial whether BCAA supplementation improves exercise endurance, and unknown whether the exercise endurance effect of BCAA supplementation requires catabolism of these amino acids. Therefore, we examined exercise capacity and intermediary metabolism in skeletal muscle of knockout (KO) mice of mitochondrial branched-chain aminotransferase (BCATm), which catalyzes the first step of BCAA catabolism. We found that BCATm KO mice were exercise intolerant with markedly decreased endurance to exhaustion. Their plasma lactate and lactate-to-pyruvate ratio in skeletal muscle during exercise and lactate release from hindlimb perfused with high concentrations of insulin and glucose were significantly higher in KO than wild-type (WT) mice. Plasma and muscle ammonia concentrations were also markedly higher in KO than WT mice during a brief bout of exercise. BCATm KO mice exhibited 43-79% declines in the muscle concentration of alanine, glutamine, aspartate, and glutamate at rest and during exercise. In response to exercise, the increments in muscle malate and alpha-ketoglutarate were greater in KO than WT mice. While muscle ATP concentration tended to be lower, muscle IMP concentration was sevenfold higher in KO compared with WT mice after a brief bout of exercise, suggesting elevated ammonia in KO is derived from the purine nucleotide cycle. These data suggest that disruption of BCAA transamination causes impaired malate/aspartate shuttle, thereby resulting in decreased alanine and glutamine formation, as well as increases in lactate-to-pyruvate ratio and ammonia in skeletal muscle. Thus BCAA metabolism may regulate exercise capacity in mice.
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PMID:Disruption of BCAA metabolism in mice impairs exercise metabolism and endurance. 2013 34


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