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

We have used 31P nuclear magnetic resonance spectroscopy (31PNMRS) to study the relation between metabolism and contraction in frog skeletal muscle. Our results show a close association between [H2PO4(1-)] and both contractile and metabolic characteristics of muscle. We suggest that this metabolite links energy requiring to energy yielding function by participating in intermediate reactions which help to determine the rates of both processes. The observed relation between [H2PO4(1-)] and force production is consistent with the suggestion of Hibberd and colleagues, that Pi is reversibly released during the transition to the major force-producing actomyosin ATPase state. Our results also suggest that force fatigue is due to the buildup of the [H2PO4(1-)] product of ATP hydrolysis and that the effect of pH on force production is largely the result of altering H2PO4(1-)/HPO4(2-). We have found that it is the extent of glycogenolysis rather than the maximum activities of glycogenolytic enzymes that determines how much glycogen is broken down following anaerobic contraction. The most likely explanation for our results is that the ATP-forming reactions of glycolysis come to equilibrium during metabolic recovery from contraction under anaerobic conditions.
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PMID:The relation between muscle contraction and metabolism: studies by 31P nuclear magnetic resonance spectroscopy. 340 25

The content of glucose 1,6-bisphosphate (G-1,6-P2), an in vitro activator of phosphofructokinase (a rate-limiting enzyme for glycolysis), and the glycolytic rate in skeletal muscle during isometric contraction have been determined. Subjects contracted the knee extensor muscles at two-thirds maximal voluntary force to fatigue. Biopsies from the quadriceps femoris muscle were obtained before and immediately after contraction. G-1,6-P2 increased in all subjects from a mean of 101 +/- 15 (SE) mumol/kg dry wt at rest to 128 +/- 24 at fatigue (P less than 0.05). Muscle glucose did not change significantly, whereas hexosemonophosphates were significantly increased after contraction. The glycogenolytic and glycolytic rate averaged 70.0 +/- 13.8 and 47.3 +/- 6.7 mmol.kg dry wt-1.min-1, respectively, and the glycolytic rate was positively correlated with the accumulation rates of fructose 6-phosphate (F-6-P) (r = 0.95, P less than 0.01) and G-6-P (r = 0.96, P less than 0.01). Phosphocreatine and ATP decreased by 87 and 17%, respectively, whereas ADP increased by 31% after contraction. These data demonstrate that intense, short-term isometric contraction results in an elevation of the muscle content of G-1,6-P2. The increase in G-1,6-P2 could not be accounted for by the side reactions of phosphoglucomutase or phosphofructokinase. It remains to be determined whether the observed increase in G-1,6-P2 is sufficient to account for the high glycolytic rate during intense exercise. The lack of increase in muscle glucose while G-6-P increased (which will inhibit hexokinase) suggests that the debranching enzyme complex was not active during contraction.
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PMID:G-1,6-P2 in human skeletal muscle after isometric contraction. 340 60

To study changes in muscle energy state during prolonged exercise, especially in relation to fatigue, muscle biopsies were obtained from seven healthy males working until exhaustion on a cycle ergometer at 68% (63-74%) of their maximal oxygen uptake. Biopsies were taken at rest, after 15 and 45 min of exercise and at exhaustion, and analysed for ATP, ADP, AMP, inosine monophosphate (IMP) and hypoxanthine content by high performance liquid chromatography (HPLC), and for creatine phosphate (CP), lactate and glycogen by enzymatic fluorometric techniques. Glycogen content at exhaustion was approximately 30% of the pre-exercise level. The CP content decreased steeply during the first 15 min of exercise (P less than 0.01) and continued to decrease during the rest of the exercise period (P less than 0.05). Pronounced increases in contents of IMP (64% P less than 0.001) and hypoxanthine (69%, P less than 0.05) were found when exhaustion was approaching. Furthermore, energy charge [EC; (ATP + 0.5 ADP)/(ATP + ADP + AMP)] was decreased at exhaustion (P less than 0.05). The increases in IMP and hypoxanthine which occurred when exhaustion was approaching during prolonged submaximal exercise together with the decrease in EC during this phase of exercise suggest a failure of the exercising skeletal muscle to regenerate ATP at exhaustion.
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PMID:ATP breakdown products in human skeletal muscle during prolonged exercise to exhaustion. 342 83

Six male subjects performed intensive cycle exercise to exhaustion after cooling their legs in water at 10-12 degrees C (muscle temperature (Tm) 28 +/- 2.6 degrees C, mean +/- SD). Exercise at exactly the same rate and duration (370 +/- 34 W, 1.5 +/- 0.2 min) was then repeated by each subject 2-5 weeks later at normal Tm (35 +/- 1.0 degrees C). Muscle biopsies were taken from the vastus lateralis muscle at rest and after exercise. The muscle tissue was freeze-dried and fragments of single fibres were dissected out. The fibres were classified and pooled into groups of type I and type II. Analyses of glycogen, glucose 6-phosphate, lactate and phosphagens were performed on pools of type-identified fibres. After exercise at reduced Tm, all subjects had higher concentrations of glucose 6-phosphate and lactate in both type I and type II fibres, and in most subjects the concentrations of ATP and phosphocreatine were lower as compared with the findings after exercise at normal Tm. During exercise the glycogen content of both fibre types decreased to a greater extent at reduced than at normal Tm in most subjects. The results suggest that during intensive dynamic exercise at reduced Tm there is a higher degree of glycolysis from glycogen in the muscle than in the normal situation. In some subjects the cause of fatigue may be related to a more rapid accumulation of lactate in the cold muscle, while in others fatigue may be related to alternative factors, e.g. low levels of ATP and phosphocreatine.
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PMID:Influence of reduced muscle temperature on metabolism in type I and type II human muscle fibres during intensive exercise. 344 42

Experiments are described which suggest that the loss of force generating capacity seen during fatigue from intermittent, submaximal voluntary contractions of the quadriceps muscle cannot be explained by any of the usual factors thought to be responsible for fatigue. During the first 30 min of intermittent contractions at 30% MVC the force generated periodically by a brief test train of 50 Hz stimulation and by brief maximal voluntary contractions both declined by 50%. Yet no significant changes were seen in the muscle lactate, ATP or phosphocreatine. Glycogen depletion was confined only to the type I and type IIA fibres, with less than 10% totally depleted. The depletion patterns indicated that the type IIAB and type IIB motor units were not recruited during the first 30 min. The central nervous system appeared to remain capable of generating full muscle activation since the force from maximal voluntary efforts declined in parallel with that from 50 Hz stimulation. We suggest that, in this type of fatigue, the loss of force may be largely due to impaired excitation/contraction coupling. This possibility is supported by the disproportionate depression of the twitches recorded between contractions compared with that from 50 Hz stimulation (low frequency fatigue). The single unit EMG recordings suggest that, in sustained and repeated submaximal contractions, muscle contractile failure is compensated by recruitment of additional motor units rather than by rate coding of those already active. During intermittent contractions large increases in the surface EMG were associated with only modest increases in firing rates. In sustained contractions when the EMG was held constant the discharge rates declined in parallel with the force. In constant force contractions involving about 35% muscle contractile failure no changes in discharge rates were seen despite substantial increases in EMG.
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PMID:Fatigue of submaximal static contractions. 347 Oct 51

Muscle phosphorylase deficiency (McArdle's disease) has conventionally been considered a disorder of glycogenolysis, and the associated impairment in oxidative metabolism has been largely overlooked. Muscle glycogen normally is the primary oxidative fuel at exercise work loads requiring more than 75-80% of maximal O2 uptake (VO2max). Evidence is presented to support the hypothesis that a limited flux through the Embden-Myerhof pathway in McArdle's disease reduces the capacity to generate NADH required to support a normal VO2max. The extent of the oxidative defect is substrate dependent; i.e., it can be partially corrected by increasing the availability of alternative oxidative substrates (e.g., glucose, free fatty acids) to working muscle. Experiments employing modification of substrate availability closely link the hyperkinetic circulatory response to exercise (i.e., an abnormally large increase in O2 transport to skeletal muscle) and the premature muscle fatigue and cramping of McArdle patients with their oxidative impairment and suggest that a metabolic common denominator in these abnormal responses may be a pronounced decline in the muscle phosphorylation potential ([ATP]/[ADP][Pi]). The hyperkinetic circulation likely is mediated by the local effects on metabolically sensitive skeletal muscle afferents and vascular smooth muscle of K+, Pi, or adenosine or a combination of these substances released excessively from working skeletal muscle. The premature muscle fatigue and cramping of McArdle patients does not appear to be due to depletion of ATP but is associated with an increased accumulation of Pi and probably ADP in skeletal muscle. Accumulations of Pi and ADP are known to inhibit the myofibrillar, Ca2+, and Na+-K+-ATPase reactions.
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PMID:The pathophysiology of McArdle's disease: clues to regulation in exercise and fatigue. 352 13

During muscular fatigue two metabolites, hydrogen ions (H+) and inorganic phosphate (Pi), increase in concentration. The effect of increase in [H+] has been modeled mathematically for a system containing creatine kinase (EC 2.7.3.2), adenylate kinase (EC 2.7.4.3), and the appropriate concentrations of their substrates. Assuming that no other equilibrium reactions are involved, the result of acidification should be a useful increase in the ratio [ATP]/[ADP]. It is also shown by a reanalysis of earlier 31P NMR studies that the observed combination of increased [H+] and increased [Pi] leads to an increase in the monobasic phosphate concentration [Pi-] that is inversely proportional to the force of contraction. This suggests that Pi- may be a direct inhibitor of the actomyosin ATPase system.
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PMID:Muscular fatigue: effects of hydrogen ions and inorganic phosphate. 353 90

Isolated soleus muscle of rat was stimulated electrically (2 Hz) for 7 min under anaerobic conditions. Isometric twitch tension decreased progressively and was 30% of the initial value at the end of stimulation. The decline in relative force was similar to that previously observed in fast twitch muscle and soleus can thus not be termed fatigue-resistant under anaerobic conditions. Phosphocreatine (PCr) decreased from (mean +/- SD) 61.1 +/- 4.4 at rest to 4.0 +/- 1.8 mmol kg-1 dry muscle (d.m.) after 7 min of stimulation, while lactate increased from 3.7 +/- 1.6 to 30 +/- 8 mmol kg-1 d.m. Energy was thus derived from complete utilization of PCr and a low rate of glycolysis resulting in an almost unchanged calculated intracellular pH. It is concluded that tension decline in soleus muscle is not due to decreased intracellular pH but is more related to the capacity to regenerate ATP at a sufficient rate. Contraction and relaxation time of the twitch remained practically constant during the stimulation period. In contrast prolonged activation of fast-twitch muscle results in a slowing of the relaxation of the twitch (Sahlin et al. 1981) and it has been suggested that this is caused by the decrease of intracellular pH. The constancy of both relaxation time and calculated pH in the fatigued soleus muscle is consistent with the hypothesis that there is a connection between these two parameters. In contrast to the twitch, relaxation of tension after a tetanus was prolonged in soleus. Hence, it appears that the rate limiting step for relaxation is different for a twitch than for a tetanus in soleus.
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PMID:Force, relaxation and energy metabolism of rat soleus muscle during anaerobic contraction. 356 37

31P NMR has been used to observe the in vivo phosphometabolite concentrations in the tail musculature from the prawn Palaemon elegans, at rest and after escape swimming and subsequent recovery. Muscular fatigue corresponds to a 60% breakdown of phosphoarginine, and a 45% increase of sugar phosphates. The pHi fell from 7.10 to 6.86. During recovery, the sugar phosphates and arginine phosphate are replenished after 20 minutes. The ATP concentration did not change throughout the experiment. The pHi was restored within 20 minutes.
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PMID:In vivo 31P NMR in crustacean muscles: fatigue and recovery in the tail musculature from the prawn Palaemon elegans. 359 47

In the process of defining the recruitment of fuel and pathway selection in rainbow trout fast-twitch white skeletal muscle, it was clear that the near-maximal myosin adenosinetriphosphatase activity during a 10-s sprint was supported solely by phosphocreatine hydrolysis. A conservative estimate of the ATP turnover was 188 mumol X g wet wt-1 X min-1. It was not until the rate and force of contraction decreased that the relative contribution of anaerobic glycogenolysis became increasingly important. Over a 10-min period of burst swimming at approximately 120% of maximum aerobic steady-state swimming velocity of trout determined in a Brett-type swim tunnel, fatigue was associated with the near-depletion of glycogen in white muscle. The ATP turnover supported by anaerobic glycogenolysis was 78 mumol X g wet wt-1 X min-1. The glycolytic pathway appeared functional at this time with control sites being identified at hexokinase and phosphofructokinase (PFK-1). PFK-1 did not appear to be inhibited by low muscle pH (pH 6.66). In another exercise protocol lasting 30 min, complete exhaustion was related to glycogen depletion. The sum of all glycolytic intermediates from glucose 6-phosphate to pyruvate at exhaustion decreased by a dramatic 80% compared with the 25% decrease for the 10-min fatigue swimming protocol. This large depletion of glycolytic intermediates was accompanied by an 80% fall in ATP, a 70-80% reduction in the ATP/ADP and phosphorylation potential, and a 2.5-fold increase in the NAD/NADH. Associated with these changes was a marked displacement of the phosphoglycerate kinase (PGK), and the combined glyceraldehyde-3-phosphate dehydrogenase-PGK reactions from thermodynamic equilibrium. As a general conclusion, fatigue and exhaustion should be viewed as a multicomponent biochemical process in response to low glycogen and not leveled at one particular step of the glycolytic pathway.
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PMID:Regulation of anaerobic ATP-generating pathways in trout fast-twitch skeletal muscle. 360 83


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