Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.3.3.1 (citrate synthase)
4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic low-frequency stimulation of rabbit fast-twitch muscle induced time-dependent increases in the concentration of the sarcolemmal Na+,K(+)-ATPase and in mitochondrial citrate synthase activity. The almost twofold increase in Na+,K(+)-ATPase preceded the rise in citrate synthase and was complete after 10 days of stimulation. We suggest that the increase in Na+,K(+)-ATPase enhances resistance to fatigue of low-frequency-stimulated muscle prior to elevations in aerobic-oxidative capacity.
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PMID:Time-dependent increases in Na+,K(+)-ATPase content of low-frequency-stimulated rabbit muscle. 132 68

The latissimus dorsi (LD) muscle is considered suitable to assist ventricular mechanical function in either cardiomyoplasty or extra-aortic-assist devices. Such application requires that this mixed-type skeletal muscle be transformed into a fatigue-resistant muscle, the adaptation of which can be elicited by chronic stimulation. In this study the LD muscles of dog and goat were subjected in situ to 12 wk of continuous electrical stimulation through intramuscular electrodes, and their myofibrillar and metabolic adaptations were compared. A gradual increase in the contraction rate of the muscle (in 10 wk from 30 to 80 contractions/min) caused the proportion of immunohistochemically identified type I fibers to increase in dog muscle from 30 to 74% and in goat muscle from 21 to 99%. Correspondingly, the anaerobic-glycolytic activity (fructose-6-phosphate kinase and lactate dehydrogenase activities) decreased by approximately 75% in both dog and goat muscles, whereas the oxidative capacity (fatty acid oxidation and citrate synthase activity) increased two- to threefold in goat LD muscle but remained unaltered in dog LD muscle. Muscular contents of high-energy phosphates and endogenous substrates were maintained, but the L-carnitine content decreased by 43% in both dog and goat. Our data further indicate that, for the monitoring of the metabolic adaptation of skeletal muscle, the ratio of activities of the oxidative and anaerobic-glycolytic pathways (e.g., citrate synthase to fructose-6-phosphate kinase activities) is a useful parameter in both dog and goat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differences in metabolic response of dog and goat latissimus dorsi muscle to chronic stimulation. 140 41

Nine men, 78-84 yr of age, participated in a dynamometer training program 2-3 times/wk, totaling 25 sessions, using voluntary maximal isometric, concentric, and eccentric right knee-extension actions (30 and 180 degrees/s). Measurements of muscle strength with a Kin-Com dynamometer and simultaneous electromyograms (EMG) were performed of both sides before and after the training period. Muscle biopsies were taken from the right vastus lateralis muscle. The total quadriceps cross-sectional area was measured with computerized tomography. Training led to an increase in maximal torque for concentric (10% at 30 degrees/s) and eccentric (13-19%) actions in the trained leg. The EMG activity increased at maximal eccentric activities. The total cross-sectional quadriceps area of the trained leg increased by 3%, but no changes were recorded in muscle fiber areas in these subjects, who already had large mean fiber areas (5.15 microns 2 x 10(3)). The fatigue index measured from 50 consecutive concentric contractions at 180 degrees/s decreased and the citrate synthase activity increased in all but one subject. The results demonstrate that increased neural activation accompanies an increase in muscle strength at least during eccentric action in already rather active elderly men and that muscle endurance may also be improved with training.
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PMID:Training can improve muscle strength and endurance in 78- to 84-yr-old men. 149 Sep 65

5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria patients and lead-exposed individuals, has previously been shown to autoxidize with generation of reactive oxygen species and to cause in vitro oxidative damage to rat liver mitochondria. We now demonstrate that chronically ALA-treated rats (40 mg/kg body wt every 2 days for 15 days) exhibit decreased mitochondrial enzymatic activities (superoxide dismutase, citrate synthase) in liver and soleus (type I, red) and gastrocnemius (type IIb, white) muscle fibers. Previous adaptation of rats to endurance exercise, indicated by augmented (cytosolic) CuZn-superoxide dismutase (SOD) and (mitochondrial) Mn-SOD activities in several organs, does not protect the animals against liver and soleus mitochondrial damage promoted by intraperitoneal injections of ALA. This is suggested by loss of citrate synthase and Mn-SOD activities and elevation of serum lactate levels, concomitant to decreased glycogen content in soleus and the red portion of gastrocnemius (type IIa) fibers of both sedentary and swimming-trained ALA-treated rats. In parallel, the type IIb gastrocnemius fibers, which are known to obtain energy mainly by glycolysis, do not undergo these biochemical changes. Consistently, ALA-treated rats under swimming training reach fatigue significantly earlier than the control group. These results indicate that ALA may be an important prooxidant in vivo.
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PMID:5-aminolevulinic acid-induced alterations of oxidative metabolism in sedentary and exercise-trained rats. 153 18

The effect of treadmill physical training (PT) on rat gastrocnemius/plantaris muscle after bilateral femoral artery ligation was investigated. To enable a comparison to be made between the susceptibility of muscles with restricted blood flow and normally perfused skeletal muscle to PT, animals without ligated femoral arteries also underwent PT. PT increased the oxidative capacity of the gastrocnemius/plantaris muscle, as judged by the activity of citrate synthase, and reduced muscle fatigue in both groups of animals. Exercise also tended to lower the activity of a marker enzyme for glycolysis, glyceraldehyde-phosphate dehydrogenase in all animals, although this only reached the level of statistical significance in the animals with ligated femoral arteries. In the animals with restricted muscle blood flow, PT increased gastrocnemius skeletal muscle blood flow and pO2 and prolonged the time taken to attain maximum muscle twitch tension. The results indicate a great susceptibility of hindlimb skeletal muscles of rats with ligated femoral arteries to PT. They also suggest that the beneficial effect of PT observed in man with chronic occlusive arterial disease (COAD) may result both from an increase in muscle blood flow and from an enhanced mitochondrial respiratory activity in the afflicted muscle.
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PMID:The effect of physical training on rat calf muscle, oxygen tension, blood flow, metabolism and function in an animal model of chronic occlusive peripheral vascular disease. 154 36

This study examined some of the physiological and performance effects of three different tapers in highly trained athletes. After 8 wk of training, nine male middle-distance runners were randomly assigned to one of three different 7-day tapers: a high-intensity low-volume taper (HIT), a low-intensity moderate-volume taper (LIT), or a rest-only taper (ROT). After the first taper, subjects resumed training for 4 wk and performed a second taper and then resumed training for 4 wk and completed the remaining taper, so that each subject underwent all three tapers. Performance was measured before and after each taper by a treadmill run to fatigue at a velocity equivalent each subject's best 1,500-m time. Voluntary isometric strength and evoked contractile properties of the quadriceps were measured before and after each taper, as were muscle glycogen concentration and citrate synthase activity (from needle biopsies) and total blood and red cell volume by 125I and 51Cr tagging. Maximal O2 consumption was unaffected by all three tapers, but running time to fatigue increased significantly after HIT (+22%). It was unaffected by LIT (+6%) and ROT (-3%) procedure. Citrate synthase activity increased significantly with HIT and decreased significantly with ROT. Muscle glycogen concentration increased significantly after ROT and HIT, and strength increased after all three tapers. Total blood volume increased significantly after HIT and decreased after ROT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Physiological effects of tapering in highly trained athletes. 830 28

Persons who suffered poliomyelitis 3 or more decades ago now report functional decline and symptoms designated as "post-polio syndrome". The objects of this investigation were to identify subjects fulfilling the criteria of this syndrome, to describe their motor impairment and resulting disabilities/handicaps, to study the adaptive changes in the muscle structure and effects of a resistance exercise program. Forty-one late-polio subjects, 40-65 years old, volunteered for the studies of motor impairment, subgroups of those volunteered to further studies of long-term and short-term adaptations. Seventy-five per cent of the subjects met the criteria for the post-polio syndrome. Complete manual muscle tests and dynamometer measurements of knee muscle strength revealed severe motor impairment predominantly in the lower extremities, the strength of the latter correlating to the degree of mobility handicap. In biopsies from the vastus lateralis muscle, type grouping was frequent. Half of the subjects demonstrated over 70% occurrence of type I fibers with negative significant correlation to strength in the female subjects. Cross-section areas of muscle fibers were on average twice the normal, with negative significant correlation to strength values in male subjects. Muscle enzymatic activity values showed large individual variations; oxidative activities (citrate synthase) were low or very low, while average glycolytic activities were nearly normal. Macro EMG and single-fiber EMG measurements in the vastus lateralis muscle demonstrated large macro motor unit potentials and increased fiber density. Neuromuscular transmission was disturbed as identified by jitter and blockings in most subjects regardless of the occurrence of new muscular symptoms. A statistically significant increase in strength (25-30%) resulted from a 6 weeks' heavy resistance exercise program, utilizing a dynamometer, without any obvious side-effects. Strength improvement was maintained for 6-12 months after training while fatigue index increased. A substantial impact on intermediate (secondary or instrumental) ADL, most severely affecting the quality of mobility, was generally found, while little effect was found on primary ADL as revealed by the Katz' ADL index, the Functional Status Questionnaire and the WHO ICIDH Classification of Handicap. The impaired motor function confirms findings in earlier studies. It also corresponds with the locomotor disabilities and handicaps. The negative correlation of strength to cross-section fiber area might result from excessive use of remaining fibers leading to a prominent hypertrophy in the weakest subjects. Enzyme activities probably reflect the pattern of everyday activities with little demands on endurance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Muscle adaptation and disability in late poliomyelitis. 183 29

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

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

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


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