Gene/Protein Disease Symptom Drug Enzyme Compound
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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 preexercise muscle glycogen content on the metabolic responses to exercise has been investigated. Seven men cycled at a work load calculated to elicit 75% of maximal oxygen uptake [211 +/- 17 (SE) W] on two occasions: 1) to fatigue (37.2 +/- 5.3 min) and 2) at the same work load and for the same duration as the first. Biopsies were obtained from the quadriceps femoris muscle before and after exercise. Before the first experiment, muscle glycogen was lowered by exercise and diet, and before the second experiment, muscle glycogen was elevated. In the low-glycogen condition (LG), muscle glycogen decreased from 182 +/- 15 at rest to 7 +/- 4 mmol glucosyl units/kg dry wt at fatigue, while in the high-glycogen condition (HG), glycogen decreased from 725 +/- 31 at rest to 353 +/- 53 mmol glucosyl units/kg dry wt at the end of exercise. Hexose monophosphates were not increased after LG exercise but increased approximately fivefold after HG exercise. Lactate increased more during HG exercise (LG = 16 +/- 5, HG = 61 +/- 7 mmol/kg dry wt; P less than or equal to 0.001), whereas IMP increased more during LG (LG = 2.8 +/- 0.6, HG = 0.9 +/- 0.2 mmol/kg dry wt; P less than or equal to 0.05). The increases in the sum of tricarboxylic acid cycle intermediates (TCAI; citrate+malate+fumarate) and acetylcarnitine (which is in equilibrium with acetyl CoA) were significantly greater during HG exercise (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of low glycogen on carbohydrate and energy metabolism in human muscle during exercise. 156 23

Recent studies in patients with long-term heart failure have suggested that intrinsic abnormalities in skeletal muscle can contribute to the development of early lactic acidosis and fatigue during exercise. The present study provides an analysis of substrate and enzyme content, fiber typing, and capillarization in skeletal muscle biopsy samples obtained at rest from the vastus lateralis in 11 patients with long-term heart failure (left ventricular ejection fraction, 21 +/- 8%) and nine normal subjects. Patients demonstrated a reduced peak exercise oxygen consumption (13.0 +/- 3.3 ml/kg/min) when compared with normals (30.2 +/- 8.6 ml/kg/min, p less than 0.001) and had an accelerated rise in blood lactate levels during exercise. In mixed fiber skeletal muscle, total phosphorylase and glycolytic enzyme activities were not different in the two groups, whereas mitochondrial enzymes involved in terminal oxidation were decreased in patients as compared with normal subjects as indicated by reductions in succinate dehydrogenase (51 +/- 15 vs. 81 +/- 17 microM/g protein/min, p less than 0.001) and citrate synthetase (26 +/- 7 vs. 43 +/- 20 microM/g protein/min, p less than 0.05). 3-Hydroxyacyl-CoA-dehydrogenase, an important enzyme mediating beta-oxidation of fatty acids, was also reduced in patients as compared with normals (18 +/- 7 vs. 27 +/- 10 microM/g protein/min, p less than 0.05). There was no difference in high-energy phosphagens or lactate concentration of mixed muscle in the two groups, whereas glycogen content was decreased in patients (262 +/- 29 vs. 298 +/- 35 microM glucosyl units/kg dry wt, p = 0.01). Patients demonstrated a reduced percentage of slow twitch type I fibers (36 +/- 7% vs. 52 +/- 22%, p less than 0.05) and had a higher percentage of type IIb fast twitch fibers (24 +/- 9% vs. 11 +/- 12%, p = 0.02), which were smaller than the type IIb fibers seen in normal subjects (p less than 0.05). In patients, the number of capillaries per fiber was decreased for type I and type IIa fibers (both, p less than 0.03), but the ratio of capillaries to cross-sectional fiber area was not different for the two groups. These data demonstrate major alterations in skeletal muscle histology and biochemistry in patients with long-term heart failure, including fiber atrophy, a decrease in percentage of composition of type I fibers, and an increase in type IIb fibers accompanied by a decrease in oxidative enzyme capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Skeletal muscle biochemistry and histology in ambulatory patients with long-term heart failure. 229 59

The changes in muscle content of carnitine and acetylcarnitine have been studied during incremental dynamic exercise. Six subjects exercised for 10 min on an ergometer at 40 and 75% of their maximal oxygen uptake (VO2 max) and to fatigue at 100% of VO2 max (about 4 min). Muscle samples were taken from the quadriceps femoris muscle at rest and after exercise. Muscle content of free carnitine was (means +/- SE) 15.9 +/- 1.7 mmol kg-1 d.wt (dry weight) at rest and remained unchanged after exercise at low intensity but decreased to 5.9 +/- 0.6 and 4.6 +/- 0.5 mmol kg-1 d.wt after exercise at 75 and 100% of VO2 max respectively. Acetylcarnine content at rest was 6.9 +/- 1.9 mmol kg-1 d.wt and increased during exercise in correspondence with the decrease in free carnitine. Muscle content of pyruvate and lactate was unchanged after exercise at 40% of VO2 max but increased at the higher intensities. The parallel increases in acetylcarnitine, pyruvate and lactate indicate that formation of acetylcarnitine is augmented when the availability of glycolytic three-carbon metabolites is high and is consistent with the idea that acetylcarnitine provides a sink for pyruvate and acetyl CoA. This could be of importance for the maintenance of an adequate level of CoA and thus function of the tricarboxylic acid cycle.
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PMID:Muscle carnitine metabolism during incremental dynamic exercise in humans. 232 59

A boy with riboflavin-responsive beta-oxidation deficiency (multiple acyl-CoA dehydrogenation deficiency) was assessed clinically and biochemically after 3 years of continuous riboflavin medication. He was diagnosed at the age of three years after an attack of a Reye's syndrome-like disease. During the 3 years of assessment he has experienced no serious disease; although short episodes of fatigue and loss of appetite have been noted. His mental and physical development has been normal. Biochemically the abnormal excretion of organic acid metabolites, characteristic of the acyl-CoA dehydrogenation deficiency, has been continuously present. Quantitatively there has been a trend to a more simple picture with ethylmalonic acid as the predominant metabolite. However, because of the large within-day variation in the excretion of all the metabolites, changes following diet and riboflavin trials must be interpreted with caution in these patients.
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PMID:Riboflavin responsive multiple acyl-CoA dehydrogenation deficiency. Assessment of 3 years of riboflavin treatment. 375 63

Alterations in enzyme activities involved in muscle energy metabolism and the muscle fiber type distribution were investigated in six subjects, ranging in age from 19-23 years, following short-term, high intensity exercise. Changes in the vastus lateralis muscle were studied prior to exercise and approximately 24 h after each of 2 consecutive days of supramaximal cycling exercise (120% VO2 max) performed intermittently as 1-min work to 4-min rest until fatigue or until 24 repetitions had been completed. The results indicated that there were no changes (P greater than 0.05) in maximal in vitro activities for representative enzymes of beta-oxidation (3-hydroxyacyl CoA dehydrogenase, HAD), the citric acid cycle (succinic dehydrogenase, SDH), glucose phosphorylation (hexokinase, HK), glycogenolysis (total phosphorylase, PHOSPH), or glycolysis (phosphofructokinase, PFK; pyruvate kinase, PK; lactate dehydrogenase, LDH) in spite of the large increase in carbohydrate utilization and glycolytic flux rate. In addition, although no change in fiber type distribution was found in the pre-exercise biopsy between days, an acute reduction (P less than 0.05) in type I fiber distribution occurred with exercise. It is concluded that supramaximal exercise performed on a short-term basis does not alter the enzymatic profile or the fiber type distribution when measured 24 h following the activity.
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PMID:Fiber type distribution and maximal activities of enzymes involved in energy metabolism following short-term supramaximal exercise. 609 Mar 24

In 11 female patients with Fibromyalgia Syndrome (FS), biopsies from the m. vastus lateralis were analyzed, in order to reveal any possible changes which might explain muscular weakness and fatigue. Nineteen healthy subjects served as a control group. Light microscopy did not show any gross histopathological findings. Fiber composition and fiber areas did not differ between the two groups, except for a greater coefficient of variation of the area of type II A fibers and of the mean fiber area in the FS group. The number of capillaries per square millimeter and also the fiber area in relation to the capillaries, was lower in the FS patients. Analyses of enzymes showed decreased levels of 3-hydroxy-CoA-dehydrogenase and citrate synthase in the patient group. The reduced oxidative enzyme levels and capillarization indicate reduced physical activity, although this does not associate with muscle fiber hypotrophy.
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PMID:Muscle fiber characteristics, capillaries and enzymes in patients with fibromyalgia and controls. 786 76

We examined the effect of Eucommia ulmoides OLIVER leaf on rat skeletal muscles together with spontaneous running-training in terms of the isozyme profile and specific activity of lactate dehydrogenase (LDH; EC 1.1.1.27) and 3-hydroxyacetyl-CoA dehydrogenase (HAD; EC 1.1.1.35). On the twenty-ninth day of the experimental period, a mandatory endurance running exercise (treadmill, 7 degrees grade) was conducted. Twenty-four hours later, the rats were sacrificed and the skeletal muscles and other organs were dissected. Due to the training, the HAD specific activity in the skeletal muscles had increased and a more oxidative metabolism had developed, which was further enhanced by the administration of the leaf. In soleus (SOL) muscle in the Eucommia leaf treated running-training group (ET), the LDH specific activity in the skeletal muscle was significantly higher than in the sedentary control group (SC). The isozyme profile of the group ET was significantly different when compared with the group SC. The changes in the LDH isozyme profile were larger in the SOL than that in extensor digitorum longus (EDL) muscle. The results show that mechanical training and the use of the leaf cooperatively increase the ability to avoid lactate accumulation in skeletal muscle. This effect is supported by the group where 67% of rats accomplished the endurance running exercise. Theses results suggest that the administration of Eucommia ulmoides OLIVER leaf along with light intensity training enhances the ability of a muscle to resist fatigue.
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PMID:Changes in lactate dehydrogenase and 3-hydroxyacetyl-CoA dehydrogenase activities in rat skeletal muscle by the administration of Eucommia ulmoides OLIVER leaf with spontaneous running-training. 1051 17

Simvastatin belongs to a class of lipid-lowering drugs which completely inhibit 3-hydroxy-3-methylglutaryl co-enzyme A (HMG CoA) reductase. The commonest adverse effects of therapy with simvastatin HMG CoA reductase inhibitors are gastro-intestinal disturbance, myositis and myopathy. Rhabdomyolysis leading to renal failure has been reported, but it appears to be very rare, except in patients also receiving cyclosporin, nicotinic acid or gemfibrozil. Here we report the case of an elderly lady who was known to have chronic renal failure, but who developed rhabdomyolysis following simvastatin therapy. Her symptoms of muscle pain, fatigue, myoglobulinuria, oliguria and pulmonary oedema appeared 48 h after the first dose of simvastatin. Simvastatin was immediately stopped, and the patient was dialysed for 1 week. Her renal function improved and came back. We suggest that extreme care should be exercised in prescribing this drug, particularly for the elderly with renal impairment.
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PMID:Simvastatin-induced rhabdomyolysis in a patient with chronic renal failure. 1127 41

Carnitine is an endogenous compound with well-established roles in intermediary metabolism. An obligate for optimal mitochondrial fatty acid oxidation, it is a critical source of energy and also protects the cell from acyl-CoA accretion through the generation of acylcarnitines. Carnitine homeostasis is affected by exercise in a well-defined manner because of the interaction of the carnitine-acylcarnitine pool with key metabolic pathways. Carnitine supplementation has been hypothesized to improve exercise performance in healthy humans through various mechanisms, including enhanced muscle fatty acid oxidation, altered glucose homeostasis, enhanced acylcarnitine production, modification of training responses, and altered muscle fatigue resistance. Available experimental clinical studies designed to assess the effect of carnitine on exercise metabolism or performance in healthy humans do not permit definitive conclusions to be drawn. In the aggregate, however, these studies suggest that carnitine supplementation does not improve maximal oxygen uptake or metabolic status during exercise in healthy humans. Carnitine administration for </=1 mo in humans increases plasma carnitine concentrations but does not increase muscle carnitine content. Additional clinical trials integrating physiologic, biochemical, and pharmacologic assessments are needed to definitively clarify any effects of carnitine on exercise performance in healthy persons.
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PMID:Supplemental carnitine and exercise. 1091 68

Mitochondrial fatty acid beta-oxidation is an important energy resource for many mammal tissues. Acyl-CoA dehydrogenases (ACADs) are a family of flavoproteins that are involved in the beta-oxidation of the fatty acyl-CoA derivatives. Deficiency of these ACADs can cause metabolic disorders including muscle fatigue, hypoglycaemia, hepatic lipidosis and so on. By large scale sequencing, we identified a cDNA sequence of 3960 base pairs with a typical acyl-CoA dehydrogenase function domain. RT-PCR result shows that it is widely expressed in human tissues, especially high in liver, kidney, pancreas and spleen. It is hypothesized that this is a novel member of ACADs family.
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PMID:Cloning and characterization of a human cDNA ACAD10 mapped to chromosome 12q24.1. 1556 Mar 74


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