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)

Isolated mouse liver mitochondria incubated with streptozotocin showed decreased rate and extent of Ca2+ uptake, and, dependent on the concentration of streptozotocin and the addition of alpha-ketoglutarate, glutamate, fluorocitrate or guanosine 5'-triphosphate, the retention of Ca2+ was either increased or decreased. Similar observations were made in liver mitochondria incubated with succinyl-CoA. In mitochondria isolated from the kidneys and islets of mice injected with streptozotocin, with and without additional injections of glucose and/or glucagon, the rate and extent of Ca2+ uptake were reduced and the release of accumulated Ca2+ was stimulated. Electron microscopy and X-ray microanalysis showed dislocation of Ca2+-containing precipitates from the mitochondria to the cytosol, and stereology disclosed increased mitochondrial volume in the B cells of streptozotocin-treated mice. State 3 and state 4 respiration with NAD-linked substrates was inhibited, but succinate oxidation was unaffected, in mitochondria isolated from the kidneys of mice treated with streptozotocin. In the kidneys of streptozotocin-injected mice, the concentration of succinyl-CoA was increased, that of citrate and guanosine 5'-triphosphate was decreased, that of glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-diphosphate was unaffected, and the metabolite concentration ratios suggested increased mitochondrial [NAD+]/[NADH] ratio and decreased cytoplasmic [NAD+]/[NADH] ratio. It is suggested as a new hypothesis that the cytotoxicity and the diabetogenicity of streptozotocin are dependent on inhibited citric acid cycle enzyme activity (primarily that of succinyl-CoA synthetase and citrate synthetase) with altered metabolite concentrations, leading to impairment of the mitochondrial uptake of Ca2+ and the activation of the pyruvate, isocitrate and alpha-ketoglutarate dehydrogenases.
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PMID:Mitochondrial changes and associated alterations induced in mice by streptozotocin administered in vivo and in vitro. 288 8

We investigated the role of thyroid hormone in the postnatal development of Ca2+ transport activity of sarcoplasmic reticulum in skeletal muscle (m. gastrocnemius-plantaris). With a Ca2+-stat method using the fluorescent dye fura 2 as Ca2+ indicator, we determined the oxalate-supported maximal Ca2+ uptake activity of sarcoplasmic reticulum in whole muscle homogenates from neonatal rats. Expressed per g tissue wet wt, the activity increased nearly 10-fold during the first 8 weeks after birth, following which time a plateau was reached. This development was absent in hypothyroid pups, in which the level of Ca2+ uptake activity remained constant at 10% of the normal adult value for at least 8 weeks. When the mothers were given 0.05% propylthiouracil in the drinking water 1 week before parturition, these pups ceased to grow after 4 weeks, had a reduced muscle protein content and a characteristic cretinous appearance. The effects of hypothyroidism could be reversed by T3 treatment (0.5 micrograms/100 g BW, daily) starting 1 or 6 weeks after birth. Treatment with bovine GH (0.1 or 0.5 IU/100 g BW; daily) starting on day 5 stimulated body growth, particularly of muscle, but was without effect on the failing development of Ca2+ uptake activity. The postnatal rise in citrate synthase and succinate dehydrogenase activities was impaired in the hypothyroid group, but lactate dehydrogenase and creatine kinase activities rose continuously, although at a reduced rate. T3 treatment also reversed these effects of propylthiouracil. At the higher dosage used bovine GH appeared to stimulate the accumulation of creatine kinase. We conclude that the failing postnatal development of sarcoplasmic reticulum Ca2+ transport activity in hypothyroidism is not secondary to the absence of GH, nor is it part of a general, indiscriminate effect, but, rather, that it indicates an absolute requirement of thyroid hormone for this particular aspect of muscle differentiation.
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PMID:The postnatal development of sarcoplasmic reticulum Ca2+ transport activity in skeletal muscle of the rat is critically dependent on thyroid hormone. 291 9

This study examined the effect of a typical collegiate swim-training program and an intensified 10-day training period on the peak tension (Po), negative log molar Ca2+ concentration (pCa)-force, and maximal shortening speed (Vmax) of the slow-twitch type I and fast-twitch type II fibers of the deltoid muscle. Over a 10-wk period, the swimmers averaged 4,266 +/- 264 m/day swimming intermittent bouts of front crawl, kicking, or pulling. The training program induced an almost twofold increase in the mitochondrial marker enzyme citrate synthase. Po of the single fibers was not altered by either the training or 10-day intensive training programs, and no significant differences were observed in the Po (kg/cm2) of type I compared with the type II fibers. The type II fiber diameters were significantly larger than the type I fibers (94 +/- 4 vs. 80 +/- 2 microns), and although fiber diameters were unaffected by the training, the 10-day intensive training significantly reduced the type II fiber diameter. The type I fibers from the trained swimmers showed pCa-force curves shifted to the right such that higher free Ca2+ levels were required to elicit a given percent of Po (for values less than 0.5 Po). The activation threshold (pCa) for the onset of tension and the pCa required to elicit one-half maximal tension were not altered by the training in either fiber type. Fiber Vmax (measured by the slack test) was fivefold higher in type II compared with type I fibers (4.85 +/- 0.50 vs. 0.86 +/- 0.04 fiber lengths/s). The exercise-training program significantly increased and decreased the Vmax of the slow and fast fibers, respectively. The 10 days of intensified training produced a further significant decrease in the Vmax of the type II fibers. After a period of detraining, the Vmax of both fiber types returned to the control level. The force-velocity relation was not significantly altered in either fiber type by the swim training; however, the intensified training significantly depressed the velocity of the type II fiber at all loads studied. The Vmax changes with exercise training are likely explained by an exercise-induced expression of fast myosin in slow fibers and slow myosin in fast fibers.
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PMID:Effect of swim exercise training on human muscle fiber function. 291 51

This study was undertaken to determine biochemical and functional (in vivo) adaptations of the rodent neonatal heart in response to a training program of endurance running. Ten day-old rats were progressively trained on a treadmill (final intensity, 21 m/min, 30% grade, 1 h/day) until 75 days of age. The training program induced 14, 57, and 24% increases in relative heart mass, skeletal muscle citrate synthase activity, and whole-body maximal O2 uptake, respectively (P less than 0.05). Cardiac myosin (ATPase) and Ca2+-regulated myofibril ATPase were both reduced by approximately 15% in trained vs. sedentary animals (P less than 0.05). In the majority of trained hearts examined, the myosin isozyme profile reflected an estimated 14 +/- 3% shift toward the V3 or low ATPase isozyme. Left ventricular functional indices during submaximal exercise, derived from a fluid-filled indwelling cannula, indicated that the trained animals maintained similar left ventricular (LV) systolic pressure, LV + the time derivative of pressure, and systemic arterial mean blood pressure compared with their sedentary counterparts. These functional parameters were maintained even though the trained animals performed with lower submaximal exercise heart rate. These findings suggest that maximal exercise capacity can be enhanced in neonatal rats even though the biochemical potential for ATP degradation in the cardiac contractile system is lowered. We speculate that the trend to maintain the myosin isozyme pattern further in the direction of the V3 isozyme in the trained neonatal rat heart may reflect a means to economize cross-bridge cycling while maintaining normal levels of ventricle performance at a given submaximal work load.
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PMID:Effects of training on biochemical and functional properties of rodent neonatal heart. 293 83

Seven hyperthyroid patients were studied by repeated muscle biopsies (vastus lateralis) before and after a period of medical treatment which averaged 10 months. The biopsies were analysed with regard to fibre-type composition, fibre area, capillary density, glycogen content and enzyme activities representing the glycolytic capacity (hexokinase, 6-phosphofructokinase), oxidative capacity (oxoglutarate dehydrogenase, citrate synthase) and Ca2+- and Mg2+-stimulated ATPase in muscle. In the pretreatment biopsy (hyperthyroid state), there was a significantly lower proportion of type I fibres (30% vs. 41%), a higher capillary density (23%), lower glycogen content (33%), and higher hexokinase activity (32%) compared with the post-treatment biopsy. No significant changes in the activity of the remaining enzymes were observed. The present study indicates that hyperthyroidism induces a transformation from type I to type II fibres in human skeletal muscle. The increase in hexokinase activity probably reflects a higher glucose utilization by skeletal muscle in order to compensate partially for the reduced glycogen content.
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PMID:Effect of hyperthyroidism on fibre-type composition, fibre area, glycogen content and enzyme activity in human skeletal muscle. 293 5

This study was undertaken to examine the influence of guanethidine monosulfate-induced sympathectomy on exercise-induced adaptations of cardiac contractile protein and on acute hemodynamic responses to exercise involving female neonatal rats. Four groups of rats were studied: 1) normal sedentary (NS), 2) normal trained (NT), 3) sympathectomized sedentary (SS), and 4) sympathectomized trained (ST). The 9-wk running program, which began at 20 days of age, induced increases in whole-body maximal O2 consumption and skeletal-muscle citrate synthase activity in both NT and ST groups compared with NS (P less than 0.05). Submaximal exercise tests demonstrated circulatory adaptations for NT, SS, and ST groups compared with NC; however, the ST group demonstrated the greatest degree of altered cardiac function (decreased heart rate, left ventricular pressure, and contractility index) during exercise. Also, significant reductions in both myosin- and Ca2+-regulated myofibril adenosinetriphosphatase (ATPase) activity and increases in the relative content of the low ATPase myosin isozyme, V3, occurred in the hearts of the two trained groups (P less than 0.05). These findings suggest that chronic exercise involving normal and sympathectomized neonatal rats improves cardiac function without compromising maximal exercise capacity. Also, the exercise-related adaptation involving myosin isozyme shifts are exaggerated when involvement of the sympathetic nervous system is reduced during training.
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PMID:Cardiac biochemical and functional adaptations to exercise in sympathectomized neonatal rats. 293 64

Sarcoplasmic reticulum vesicles and mitochondria were prepared from red and white skeletal muscles of the rabbit. The preparations were characterized in terms of their specific activities of citrate synthase, basal (Mg2+-dependent) and Ca2+-dependent ATPase (the latter two in the presence of NaN3 and ouabain), and their specific carbonic anhydrase activities were determined. Skeletal muscle mitochondria had high specific activities of citrate synthase (700-1200 mu. mg protein-1) and low carbonic anhydrase activities (0.1-0.4 u. ml mg protein-1). The latter are likely to be due to a contamination of the preparations with sarcoplasmic reticulum (s.r.) Preparations of s.r. vesicles showed negligible activities of citrate synthase and the expected differing patterns of basal and Ca2+-dependent ATPase in red and white muscles. Specific carbonic anhydrase activities in s.r. from both muscle types were high (2-4 u. ml mg protein-1). The highest carbonic anhydrase activity, 11 u. ml mg protein-1, was found in s.r. from rabbit m. masseter. The inhibition constant of s.r. carbonic anhydrase towards acetazolamide was 4-6 X 10(-8) M and similar but not identical to that of cytosolic carbonic anhydrase II. It appears possible that the carbonic anhydrase II-like enzyme previously found by us in muscle homogenates (Siffert & Gros, 1982) originates from the s.r. Histochemical studies using the dansylsuphonamide method described previously (Dermietzel, Leibstein, Siffert, Zamboglou & Gros, 1985) showed an intracellular pattern of carbonic anhydrase staining compatible with the presence of the enzyme in s.r.: spots homogeneously distributed across the fibre cross-sections in transversely sectioned fibres and thin, longitudinally oriented, bands in longitudinally sectioned fibres. It is estimated that s.r. carbonic anhydrase accelerates CO2 hydration within the s.r. approximately 1000-fold. Thus, CO2 and HCO3- react fast enough to provide a rapid source and sink for protons leaving and entering the s.r. in exchange for Ca2+.
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PMID:Carbonic anhydrase in the sarcoplasmic reticulum of rabbit skeletal muscle. 293 36

Eleven patients diagnosed and treated for congestive cardiomyopathy (COCM) of unknown aetiology, and another 10 patients, with congestive alcoholic heart muscle disease (ACOCM) were studied. Muscle biopsy samples were obtained from the vastus lateralis (VL) and the gastrocnemius (G) muscles. In part of the sample muscle the fibre pattern was classified by means of ATPase activity staining, a technique based on the pH lability of the fibres concerned. Fibre typing and area measurements were carried out by light microscope. The other part of the sample was used as muscle homogenate of which the Ca2+-activated ATPase activity as well as citrate synthetase (CS) and aldolase activities were measured. No significant difference was found in these enzyme activities between the two groups of patients. The proportion of the slow twitch (ST) fibres in the VL, mainly in the patients with ACOCM, was lower as compared to data for healthy subjects. A similar tendency was revealed for G. In both muscles tested, the area of ST fibres was smaller in the ACOCM group. The fast twitch (FT) fibre area proved to be slightly different in the two groups of subjects tested. Occurrence of degenerative signs in the histological tests was higher in the ACOCM than in the COCM group. It was concluded that differences in the skeletal muscles of patients with ACOCM and COCM may primarily account for the alcoholism. The disease of the heart muscle has little effect on the function of skeletal muscle. Even so, a low amount or lack of physical activity may have an unfavourable influence on the skeletal muscles of patients with heart muscle disease.
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PMID:Skeletal muscle biopsy studies of cardiac patients. 296 68

The present study compares the time courses of the early changes in parvalbumin content, in the properties of the sarcoplasmic reticulum (SR) and in activity and isozyme patterns of metabolic enzymes in chronically (12 h/day) stimulated fast twitch tibialis anterior (TA) muscle of the rabbit. Under the chosen conditions of stimulation, the first significant changes appeared after 6 days. Except for the delayed reduction in pyruvate kinase, the time course of the changes were the same. After 14 days of stimulation, parvalbumin decreased to 37% and Ca2+-ATPase activity of the SR to 29% of normal values. The transformation of the SR was also reflected by a 64% decrease of the 115000-Mr Ca2+-pumping peptide and a 5-fold increase in a 30000-Mr peptide. Following an identical time course, the mitochondrial activities of citrate synthase, 3-hydroxyacyl-CoA dehydrogenase and ketoacid-CoA transferase increased 2.9, 3.0 and 3.7-fold respectively. A similar time course was observed in the M to H-type transition of the lactate dehydrogenase isozymes. The cause of these changes is discussed as it relates to altered transcriptional and/or translational activities. It is suggested that an increase in free intracellular Ca2+ caused by increased contractile activity, which is then perpetuated by the decrease in Ca2+-binding and sequestering capacities, might be the signal for such altered synthetic activities.
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PMID:Relationships between early alterations in parvalbumins, sarcoplasmic reticulum and metabolic enzymes in chronically stimulated fast twitch muscle. 622 11

This study was designed to test the hypothesis that rats trained with marked reductions in exercise heart rate respond with adaptations indicative of increased intrinsic myocardial performance. Therefore, we measured changes in maximum work capacity (VO2max), biochemical-functional indexes of cardiac contractile capacity, and skeletal muscle oxidative capacity in normal-trained (NT) rats and in rats trained while receiving the selective cardiac beta 1-blocking drug atenolol (AT). Training consisted of treadmill running at approximately 80% VO2max (untrained) for 1-h duration, 6 days/wk, for a total of 8 wk. Exercise heart rate of the AT group was markedly reduced and averaged 140 beats/min below the NT group for any given session. Compared with sedentary controls, VO2max was increased by 11%, and red vastus lateralis muscle citrate synthase activity was increased by 28% in both AT and NT groups (P less than 0.05). There were no differences between trained and nontrained groups with regard to Ca2+-regulated myofibril adenosinetriphosphatase. In situ derived left ventricular pressure and the maximum rate of left ventricular pressure development were not augmented relative to sedentary control values when the trained hearts were either stimulated inotropically or maximally afterloaded . These findings suggest that maximum exercise capacity can be enhanced in rodents conditioned with and without limited elevation in exercise heart rate; however, this reduction of exercise heart rate acceleration does not provide a stimulus to enhance the intrinsic functional capacity of the rodent heart.
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PMID:Adaptive responses of rats trained with reductions in exercise heart rate. 623 46


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