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

1 The accumulation of glucose in the brain produced by the administration of phosphatidylserine liposomes into mice has been studied by measurement of the cerebral contents of glycolytic intermediates and high-energy compounds. 2 With a normal supply of oxygen to the brain, inhibition of glycolysis is indicated mainly at the phosphofructokinase step. The ratio of glucose-6-phosphate to fructose-1,6-diphosphate increased, whereas the levels of pyruvate and especially lactate decreased. 3 Under conditions of cerebral ischaemia, the administration of phosphatidylserine delays glycogen mobilization and ATP use. As a consequence of decreased energy utilization, the brain adenylate energy charge remains at a high level. 4 It is concluded that the phosphatidylserine-induced glucose accumulation in the brain is due to reduced energy expenditure and therefore to a decrease in carbohydrate consumption. The inhibition of glycolysis by the high level of adenylate energy charge is probably the control mechanism explaining the decreased carbohydrate utilization.
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PMID:Pharmacological effects of phosphatidylserine liposomes: regulation of gylcolysis and energy level in brain. 46 67

Capillary supply and oxidative and glycolytic enzyme activities were determined in muscle biopsies from the tibialis anterior muscle in six prior polio patients and a control group. The polio patients, who had paresis and atrophy, but were able to walk normally by making maximal use of all remaining anterior tibial motor units, showed type I (slow-twitch) muscle fibre predominance with a mean (SD) of 98 (2%) type I fibres versus 81 (8)% in the controls (p less than 0.01) and muscle fibre hypertrophy, the average type I fibre cross-sectional area being 108% (p less than 0.005) larger than in the controls. The number of capillaries per muscle fibre was not significantly different from that in the control group, but with the increased muscle fibre area in the polio patients, the capillary density was significantly lower. The number of capillaries in contact with type I fibres relative to fibre area was 40% lower in the patients than in the controls (p less than 0.005). The levels of citrate synthase and phosphofructokinase were significantly lower (38% and 33%, respectively, p less than 0.05) in the patients than in the controls, indicating decreased oxidative and glycolytic potentials in the muscle fibres of the polio patients. It is proposed that the abnormal high-frequency activation of all remaining motor units during each step cycle recorded in these patients constitutes a stimulus for type I muscle fibre predominance and hypertrophy but that the overall low muscle usage results in a decreased stimulation of capillary proliferation and mitochondrial enzyme synthesis. The low capillary density and decreased oxidative and glycolytic enzyme potentials might be important factors for the development of muscle weakness, fatigue and muscle pain, which are commonly occurring symptoms in patients with prior poliomyelitis.
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PMID:Prior poliomyelitis-reduced capillary supply and metabolic enzyme content in hypertrophic slow-twitch (type I) muscle fibres. 203 Mar 51

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

Skeletal muscle has an inherent biochemical phenotypic plasticity that provides the possibility for it to be remodeled into a "heart-like" muscle for use in cardiac-assist devices. The purpose of this study was to chronically stimulate skeletal muscle electrically to transform the biochemical capacities of the three major subcellular systems (i.e., metabolic, calcium regulating, and contractile) to resemble those of heart muscle. The latissimus dorsi muscle (LDM) of mongrel dogs weighing 22-27 kg was stimulated via the thoracodorsal nerve at 2 Hz for 6-8 wk. This stimulation protocol reduced the phosphorylase (glycogenolytic) and phosphofructokinase (glycolytic) activities by 70%. The aerobic (citrate synthase activity) and fatty acid oxidative (3-hydroxyacyl-CoA dehydrogenase activity) capacities were not significantly increased by chronic stimulation and remained at about one-fourth those in the canine heart. The calcium-dependent sarcoplasmic reticulum adenosinetriphosphatase (ATPase) activity in the microsomal fraction, which was sixfold greater in the nonstimulated LDM than in the heart, was reduced by electrical stimulation to a level similar to that of the dog heart. The contractile capacity was evaluated by determining the percentage of types I and II fibers, the myofibrillar ATPase activity, and the proportion of myosin isoforms. The transformed muscle was comprised of 93 +/- 2% type I fibers, a myofibrillar ATPase activity similar to that in heart with primarily a slow-twitch muscle myosin isoform. In conclusion, electrical stimulation of canine LDM at 2 Hz for 6-8 wk resulted in two of the three biochemical systems, which confer physiological expression and fatigue resistance to muscle being transformed to resemble those of the myocardium.
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PMID:Biochemical transformation of canine skeletal muscle for use in cardiac-assist devices. 214 Aug 28

Fatigue of isolated gastrocnemius muscles from R. pipiens leads to a marked increase in the proportion of phosphofructokinase bound to the particulate fraction and a decrease in the binding of lactate dehydrogenase, pyruvate kinase, creatine phosphokinase and glyceraldehyde-3-phosphate dehydrogenase. Only the proportion of aldolase bound to the particulate fraction was unaffected by fatigue. This pattern was unchanged when fatigued muscles were extracted at pH 6.5 rather than 7.5. Thus, muscle fatigue leads to opposite changes in the binding of the glycolytic enzymes.
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PMID:The effect of fatigue on the binding of glycolytic enzymes in the isolated gastrocnemius of Rana pipiens. 280 95

The effect of nadolol at a dose of 1 mg kg-1, i.v. on the ischaemic myocardial metabolism has been examined in the dog. Ischaemia was induced by ligating the left anterior descending coronary artery for 3 min, and nadolol was injected 5 min before ligation. Ischaemia caused myocardial metabolic changes; it decreased energy charge potential and inhibited glycolytic flux through phosphofructokinase reaction. Pretreatment with nadolol lessened the decrease in energy charge potential and the inhibition of glycolytic flux being caused by ischaemia. Nadolol may have a beneficial effect on the ischaemic myocardium.
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PMID:Effect of nadolol, a beta-adrenoceptor blocking agent, on myocardial metabolism in the dog ischaemic heart. 288 50

Glucose 1,6-bisphosphate (G-1,6-P2) is a potent activator of phosphofructokinase (PFK) and an inhibitor of hexokinase in vitro. It has been suggested that increases in G-1,6-P2 are a main means by which PFK can achieve significant catalytic function in vivo despite falling pH and that increases in G-1,6-P2 will inhibit hexokinase in vivo. The purpose of the present study was to determine whether contraction-induced changes in flux through PFK and hexokinase are associated with changes in G-1,6-P2 in skeletal muscle. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal O2 uptake (VO2max) and to fatigue [4.8 +/- 0.6 (SE) min] at 100% VO2max. Biopsies were obtained from the quadriceps femoris muscle at rest and after each work load and analyzed for G-1,6-P2. G-1,6-P2 averaged 111 +/- 13 mumol/kg dry wt at rest and 121 +/- 16, 123 +/- 15, and 123 +/- 11 mumol/kg dry wt after the low-, moderate-, and high-intensity exercise bouts, respectively (P less than 0.05 for all means vs. rest). Flux through PFK was estimated to increase exponentially as the exercise intensity increased and muscle pH decreased at the higher work loads, whereas flux through hexokinase was estimated to increase during exercise at 40 and 75% VO2max but decrease sharply at 100% VO2max. These data demonstrate that flux through neither PFK nor hexokinase is mediated by changes in G-1,6-P2 in human skeletal muscle during short-term dynamic exercise.
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PMID:Carbohydrate metabolism in human skeletal muscle during exercise is not regulated by G-1,6-P2. 296 83

The fatigue characteristics and the activities of oxidative and glycolytic enzymes were determined in tetrodotoxin (TTX)-induced disuse muscles and in muscles of animals recovering from TTX-induced disuse (TTX-rec). In addition, the effects of additional daily exercise (grid-climbing and swimming) on the fatigue and metabolic profiles of muscles from TTX-rec and control animals were investigated. The activities of citrate synthase (CS), phosphofructokinase (PFK), and alpha-glycerophosphate dehydrogenase (alpha-GPD) were depressed following 28 days of inactivity produced by the chronic neural application of TTX. The response of these muscles to a pattern of stimulation that has been used to classify fast-twitch motor units according to their fatigability (6) (330 ms, 40 Hz, l/s, 4 min) was not affected to any great extent by inactivity, except for a loss in the ability to summate or maintain forces during each 330-ms burst, as fatigue developed. After 28 days of recovery, the concentration of CS had returned to normal, whereas the concentrations of PFK and alpha-GPD remained depressed. TTX-rec muscles, on the other hand, appeared more resistant to fatigue than control muscles, based on several indices of muscle fatigue. Control and TTX muscles responded similarly to daily training. Swimming but not climbing increased the activity of CS and the fatigue resistance of the muscle. Neither exercise influenced the activity of PFK and alpha-GPD. Although the activity of CS was influenced by the level of neuromuscular usage, the former did not appear to play a dominant role in determining the fatigue resistance of the muscle, emphasizing the need to consider other factors as primary determinants of muscle fatigue.
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PMID:Recovery of muscle from tetrodotoxin-induced disuse and the influence of daily exercise. 2. Muscle enzymes and fatigue characteristics. 297 Sep 77

The effect of fatigue (running to exhaustion) on the Vmax activity of the key glycolytic enzymes measured at saturating substrate concentrations in muscles, liver and brain of sedentary and trained (running on a treadmill one h/day at 20 m/min, five days/week for six months) female Zucker fatty rats and their lean littermates was investigated. In the sedentary rats, fatigue increased the activity of phosphofructokinase (PFK) in the red vastus muscle by 82% in lean, and 120% in obese rats. In the trained rats, fatigue increased PFK activity by 28% in the white vastus muscle of lean rats. In the lean animals, hexokinase (HK) activity was decreased by 26% in the red vastus of sedentary rats, and by 29% in the white vastus of trained rats upon fatiguing. Pyruvate kinase (PK) activity was also decreased by 29% in the white vastus of fatigued lean animals. Training by itself had no effect on the activity of glycolytic enzymes, except PK activity which was increased by 27% in the cortex of the lean animals. It is concluded that in the Zucker rat, these glycolytic enzymes may play a differential role in regulating glycolysis during exercise and fatigue; the extent of their involvement differs depending upon the type of tissue studied and exercise. In view of the reported short half-life (7-17 h) of PFK and its covalent modification, it is suggested that the total content and/or phosphorylation status of the enzyme may be affected in animals subjected to long-term fatigue.
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PMID:Effect of exercise on glycolytic enzymes of Zucker fatty rats. 297 74

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


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