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

The regulation of glycogenolysis in human muscle during isometric and dynamic exercise has been investigated. Total glycogen phosphorylase and synthase activities were unchanged during exercise. The fraction of phosphorylase in the alpha form at rest was estimated to be 20%, but the data indicate that the in vivo activity was low and critically dependent on the concentration of inorganic phosphate (Pi) in the muscle. Phosphorylase alpha increased initially 2.4-fold during isometric contraction and 1.6-fold during maximal bicycle exercise but reverted to or below the resting value at fatigue/exhaustion. At rest synthase I was 17-48% of the total activity but decreased during exercise to about half of this value. The reciprocal changes in phosphorylase and synthase correlate with the enhanced rate of glycogenolysis during exercise. Michaelis constant (Km) for Pi was 27 mmol . l-1 for phosphorylase alpha and 7 mmol . l-1 for alpha + b. From consideration of the changes in Pi during exercise (to 20-30 mmol . l-1) it was concluded that Pi is one of the main factors determining phosphorylase activity and provides a link between phosphocreatine breakdown and glycogen utilization in muscle.
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PMID:Regulation of glycogenolysis in human muscle at rest and during exercise. 681 2

The basic scientific achievements of the Department of Biochemistry of Muscles organized at the Academy of Sciences of Ukrainian SSR in 1944 are presented in this short historical overview. The basic guidelines for activities in the scientific field are as follows: study of biochemical processes in the working muscles as well as during misfunctions and disabilities, processes of adenine nucleotides exchange and ammonia creation, biochemical characterization of Ca2+ and H+ transport through the plasma and sarcoplasmic reticulum membranes. It is shown that creatine and creatine phosphate as well as adenine nucleotide content and metabolism affect the muscle functioning, glycogen metabolism proceeds simultaneously with the lowering of content of inorganic phosphate. The facts of glucose phosphorylation and its conversion via glycolytic pathways and the backward reaction of glycolysis (the aerobic synthesis of phosphopyruvate, glycogen synthesis from glucose in the presence of phosphorylase) were determined. After the muscle work up to tiredness adenine nucleotide depletion is not limited by its dephosphorylation, but goes up to formation of inosine acid and ammonia. Deamidation is shown to be in myofibrillar fraction and in sarcoplasmic reticulum of the skeletal muscle. Deamidation activity is not registered in myocardium myofibrillar fraction but it is registered in sarcoplasmic reticulum. AMP-phosphohydrolase and adenosine desaminase were found in membranes of the sarcoplasmic reticulum. The decrease in activity of all enzymes mentioned above is registered during myocardium hypertrophy, because of aorta narrowing. These data permit creating the methods for obtaining substance "adenosine phosphate" for treatment of cardiac pathologies. Glutaminase was found to be active in the muscles. This activity depended on the organism functioning. The ammonia usage by the muscle cells goes with glutamine synthesis and consumption of energy of ATP, e.g. protein amidation. The later is of all-biological significance and is used in the fields of medicine actualls concerned with the following fact: the velocity of hydrolysis of amidated protein is different for such pathology as epilepsia, tuberculosis, poisoning with manganese oxides. The methods for diagnostics of the above pathological states were developed on this basis. It is proved that glutamine nitrogen can be also used in the reaction of transamination, particularly during synthesis of purines, inosine acid and it is stored in a form of glutaminic acid. Changes in carbohydrate and phosphorus metabolism, in nitrogen and energetic exchanges and mitochondria overfilling with calcium were determined under E-avitaminosis dystrophy.(ABSTRACT TRUNCATED)
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PMID:[Department of the Biochemistry of Muscles]. 757 Oct 74

McArdle's disease is defined as a lack of functional muscle glycogen phosphorylase. Analysis of the myophosphorylase gene has demonstrated substantial heterogeneity in the mutations that cause the disease, but in almost all individuals, the molecular phenotype is the absence of the protein in skeletal muscle. Muscle glycogen phosphorylase is a major repository of vitamin B6 in the body, accounting for at least 80% of the total body pool. In McArdle's patients, this pool is therefore missing, introducing the possibility that vitamin B6 metabolism might be altered in these individuals. Preliminary data have shown that McArdle's patients show signs of a subclinical vitamin B6 deficiency, and that oral vitamin B6 supplementation can improve vitamin B6 status and enhance fatigue resistance in muscle.
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PMID:McArdle's disease: molecular genetics and metabolic consequences of the phenotype. 760 21

Myophosphorylase deficiency or McArdle's disease is rarely recognized in childhood. The onset is generally in adolescence or in adult age with exercise intolerance, muscle cramps and myoglobinuria. Two siblings of 6 and 2 years of age are described. The first patient showed early fatigue and both had elevated CK levels. Morphological and biochemical studies of muscle biopsies revealed a defect of myophosphorylase.
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PMID:[Muscle phosphorylase deficiency in childhood. A case report]. 780 67

1. The influences of age (5, 13 and 25-month-old rats), overload as obtained by denervation of synergists, and training on the metabolic capacity, relative muscle cross-sectional area occupied by each fibre type, capillarization and fatigue resistance of the rat m. plantaris were investigated. 2. Creatine kinase, phosphorylase and citrate synthase activities were lower in muscles of 25 than in those of 13-month-old rats (P < 0.001). 3. Overload resulted in an increased relative area of type I and IIa fibres at all ages (P = 0.001). 4. Capillary density decreased with overload and increasing age (P < 0.001). 5. Fatigue resistance was higher in muscles of 13 than in those of 5-month-old rats (P < 0.05), and increased with overload (P < 0.05) at all ages. 6. Fatigue resistance of the whole muscle was not closely related to its oxidative capacity in contrast to what is generally found for single fibres or motor units.
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PMID:Metabolic capacity, fibre type area and capillarization of rat plantaris muscle. Effects of age, overload and training and relationship with fatigue resistance. 840 55

We evaluated the physiological, histochemical, and biochemical consequences of inhibiting contractile activity in rat skeletal muscles with botulinum toxin A (BTX). Contractile activity was entirely eliminated 12-18 h after a single, focal, intramuscular injection of BTX into the rat tibialis anterior muscle (TA). Neuromuscular transmission remained completely inhibited for 10-12 days, then slowly recovered. BTX-treated muscles exhibited a lower resistance to both high- and low-frequency fatigue at 7 and 14 days after injection, but contractile force recovered more rapidly in treated TA after fatigue. Treated TA showed a twofold increase in the activity of the triglyceride hydrolase enzyme lipoprotein lipase (LPL) and a comparable increase in the relative abundance of LPL steady-state mRNA. In contrast, there was a 28% reduction in protein levels of the muscle isozyme of glycogen phosphorylase (MGP) and a 70% decrease in relative MGP transcript levels. Similar changes in relative transcript levels of LPL and MGP were observed in the predominantly fast-twitch extensor digitorum longus after BTX injection, but relative LPL and MGP mRNA levels were not altered in predominantly slow-twitch soleus. Histochemical evidence indicated that fast-twitch glycolytic fibers had increased lipid content. These biochemical alterations were reversed 120 days after BTX treatment despite persistent atrophy.
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PMID:Botulinum-induced muscle paralysis alters metabolic gene expression and fatigue recovery. 876 7

Squid (Lolliguncula brevis) were exercised at increasing swimming speeds to allow us to analyze the correlated changes in intracellular metabolic, acid-base, and energy status of the mantle musculature. Beyond a critical swimming velocity of 1.5 mantle lengths/s, an intracellular acidosis developed that was caused by an initial base loss from the cells, the onset of respiratory acidification, and, predominantly, octopine formation. The acidosis was correlated with decreasing levels of phospho-L-arginine and, thus, supported ATP buffering at the expense of the phosphagen. Monohydrogenphosphate, the actual substrate of glycogen phosphorylase accumulated, enabling glycogen degradation, despite progressive acidosis. In addition to octopine, succinate, and glycerophosphate accumulation, the onset of acidosis characterizes the critical velocity and indicates the transition to a non-steady-state time-limited situation. Accordingly, swimming above the critical velocity caused cellular energy levels (in vivo Gibbs free energy change of ATP hydrolysis) to fall. A minimal value was reached at about -45 kJ/mol. Model calculations demonstrate that changes in free Mg2+ levels only minimally affect ATP free energy, but minimum levels are relevant in maintaining functional concentrations of Mg(2+)-complexed adenylates. Model calculations also reveal that phosphagen breakdown enabled L. brevis to reach swimming speeds about three times higher than the critical velocity. Comparison of two offshore squid species (Loligo pealei and Illex illecebrosus) with the estuarine squid L.brevis indicates that the latter uses a strategy to delay the exploitation of high-energy phosphates and protect energy levels at higher than the minimum levels (-42 kJ/mol) characterizing fatigue in the other species. A more economical use of anaerobic resources and an early reduction in performance may enable L. brevis to tolerate more extreme environmental conditions in shallow estuarine waters and even hypoxic environments and to prevent a fatal depletion of energy stores.
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PMID:Metabolic and energy correlates of intracellular pH in progressive fatigue of squid (L. brevis) mantle muscle. 894 80

We evaluated 4 women with chronic fatigue and myalgias. Two had proximal weakness. All had elevated serum creatine kinase levels, but none was diagnosed with myopathy until electrodiagnostic studies revealed myotonic or complex repetitive discharges predominantly in paraspinal muscles. Histopathology of paraspinal muscles revealed vacuolar myopathies with glycogen storage; biochemical assays revealed phosphorylase deficiency in 1. Since vacuolar myopathies may affect paraspinal muscles more than limb muscles, electromyographic and histopathologic studies of paraspinal muscles may be required for diagnosis.
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PMID:Vacuolar myopathies in adults with myalgias: value of paraspinal muscle investigation. 932 92

Muscle proteins turn over slowly and there are minimal diurnal changes in the size of the muscle protein pool in response to feeding and fasting. Nitrogen balance and tracer studies indicate that protein oxidation and net protein breakdown (degradation--synthesis) is not increased during dynamic exercise at intensities of < or = 70% VO2max. An imbalance between muscle protein synthesis and degradation does exist during one leg knee extensor exercise and during two legged cycling in patients with glycogen phosphorylase deficiency. In these latter cases amino acids liberated from the protein pool are used for synthesis of TCA-cycle intermediates and glutamine. Six amino acids are metabolized in resting muscle: leucine, isoleucine, valine, asparagine, aspartate and glutamate. Only leucine and part of the isoleucine molecule can be converted to acetylCoA and oxidized. The carbon skeleton of the other amino acids is used for synthesis of TCA-cycle intermediates and glutamine. The six amino acids provide the amino groups and the ammonia for synthesis of glutamine and alanine, which are released by muscle in excessive amounts. About half of the glutamine release from muscle originates from glutamate taken up from the blood. Glutamine produced by muscle is an important fuel and regulator of DNA and RNA synthesis in mucosal cells and immune system cells and fulfils several other important functions in human metabolism. The alanine aminotransferase reaction functions to establish and maintain high concentrations of TCA-cycle intermediates and a high TCA cycle flux in the first minutes of exercise. A gradual increase in leucine oxidation subsequently leads to a carbon drain on the TCA-cycle in glycogen depleted muscles and may thus reduce the maximal flux in the TCA-cycle and lead to fatigue. Deamination of amino acids and glutamine synthesis present alternative anaplerotic mechanisms in glycogen depleted muscles but only allow exercise at 40-50% of Wmax. It is proposed that the maximal flux in the TCA-cycle is reduced in glycogen depleted muscles due to insufficient TCA-cycle anaplerosis and that this presents a limitation for the maximal rate of fatty acid oxidation. Interactions between the amino acid pool and the TCA-cycle thus seem to play a central role in the energy metabolism of the exercising muscle.
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PMID:Protein and amino acid metabolism in human muscle. 978 36

Stimulated by recent (13)C and (31)P NMR studies of exercising muscle, we propose a model of the energetics of contraction. Previous studies of energetics have followed energy consumption. However, the rapidity of contraction, in 10-40 msec, requires that energy be delivered rapidly, so that the muscle has power requirements of rapid energy expenditure that are ultimately met by the slower averaged consumption of carbon and oxygen from blood. We propose that energy is supplied in milliseconds by glycogenolysis and that between contractions, glycogenesis refills the pools. The energy for glycogenesis is supplied by oxidative phosphorylation. This mechanism utilizes the rapid conversion of glycogen phosphorylase, the "fight-or-flight" enzyme, to its active form. Lactate is necessarily generated by this pathway to serve as a time buffer between fast and slow energy needs, which resolves the paradoxical generation of lactate in well oxygenated tissue. Consequences of the glycogen shunt are compatible with numerous biochemical and physiological experiments. The model provides a possible mechanism for muscle fatigue, suggesting that at low but nonzero glycogen concentrations, there is not enough glycogen to supply millisecond energy needs.
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PMID:The "glycogen shunt" in exercising muscle: A role for glycogen in muscle energetics and fatigue. 1120 49


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