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)

Subjective fatigue was quantified before and 20 days after uncomplicated elective abdominal surgery in 12 patients and compared with changes in heart rate, enzyme activities and skeletal muscle substrates before and after bicycle exercise for 10 min at 65 per cent of patients' preoperative maximum work capacity. Fatigue increased from a mean(s.e.m.) preoperative level of 2.5(0.5) arbitrary units to 4.6(0.5) on postoperative day 20 (P less than 0.01). Body-weight, triceps skinfold thickness and arm circumference decreased postoperatively (P less than 0.02). Postoperative values of muscle enzyme activities indicative of oxidative phosphorylation capacity (citrate synthase and 3-OH-acyl coenzyme A dehydrogenase) were lower than preoperative values (P less than 0.05). Lactate dehydrogenase was unaltered and resting values of muscle glycogen and adenosine triphosphate were higher after operation (P less than 0.05). In response to exercise, heart rate, muscle glucose, glucose-6-phosphate and lactate increased (P less than 0.05), while muscle glycogen and creatine phosphate decreased (P less than 0.05). Increase in postoperative fatigue correlated with the increase in heart rate (P less than 0.05), while no significant correlations were found between fatigue and muscle parameters. Our results suggest that lack of exercise and malnutrition may be of importance in the decrease in work capacity and in fatigue after operation.
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PMID:Skeletal muscle enzyme activities and metabolic substrates during exercise in patients with postoperative fatigue. 232 98

This study examined if there was a relationship between the aerobic-oxidative potential of skeletal muscle and the metabolic and force recovery after intense exercise. Eleven male subjects performed three bouts of unilateral knee extensions using an isokinetic device. Sixty seconds of rest separated bouts. Muscle biopsies were taken from the vastus lateralis prior to exercise, immediately after bout 2 and before bout 3. Samples were analysed for adenosine triphosphate (ATP), adenosine diphosphate (ADP), inosine monophosphate (IMP), creatine phosphate (CP) and lactate contents and citrate synthase (CS) activity. Peak torque at the end of bout 2 was 45% of initial peak torque of bout 1 (IPT1). With recovery, initial peak torque of bout 3 (IPT3) was 81% of IPT1. Peak torque after recovery (IPT3/IPT1) was related to CS activity (r = 0.69). ATP, CP and ATP/ADP decreased with exercise. ADP, IMP and lactate increased. With recovery, ATP and CP remained depressed. IMP and lactate remained elevated. ATP/ADP and ADP returned towards 'normal', but only the latter attained resting levels. When analysing the individual responses the following correlations were found. After recovery, ATP/ADP (r = 0.57), ATP/ADP relative to rest (r = 0.71), lactate (r = -0.62), CP (r = 0.75) and CP relative to rest (r = 0.83) were related to CS activity. The changes in lactate (r = -0.76) and CP (r = 0.79) during recovery (bout 3-bout 2) were also related to CS activity. The results suggest that the recovery of force and the 'normalization' of metabolite contents after short-term, intense exercise are dependent on the aerobic-oxidative potential of skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of recovery from intensive exercise to the oxidative potential of skeletal muscle. 235 45

Adaptations in skeletal muscle in response to progressive hypobaria were investigated in eight male subjects [maximal O2 uptake = 51.2 +/- 3.0 (SE) ml.kg-1.min-1] over 40 days of progressive decompression to the stimulated altitude of the summit of Mt. Everest. Samples of the vastus lateralis muscle extracted before decompression (SL-1), at 380 and 282 Torr, and on return to sea level (SL-2) indicated that maximal activities of enzymes representative of the citric acid cycle, beta-oxidation, glycogenolysis, glycolysis, glucose phosphorylation, and high-energy phosphate transfer were unchanged (P greater than 0.05) at 380 and 282 Torr over initial SL-1 values. After exposure to 282 Torr, however, representing an additional period of approximately 7 days, reductions (P less than 0.05) were noted in succinic dehydrogenase (21%), citrate synthetase (37%), and hexokinase (53%) between SL-2 and 380 Torr. No changes were found in the other enzymes. Capillarization as measured by the number of capillaries per cross-sectional area (CC/FA) was increased (P less than 0.05) in both type I (0.94 +/- 0.8 vs. 1.16 +/- 0.05) and type II (0.84 +/- 0.07 vs. 1.05 +/- 0.08) fibers between SL-1 and SL-2. This increase was mediated by a reduction in fiber area. No changes were found in fiber-type distribution (type I vs. type II). These findings do not support the hypothesis, at least in humans, that, at the level of the muscle cell, extreme hypobaric hypoxia elicits adaptations directed toward maximizing oxidative function.
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PMID:Operation Everest II: adaptations in human skeletal muscle. 274 6

Patients with heart failure frequently exhibit abnormal skeletal muscle metabolic responses to exercise, as assessed with 31P NMR. To investigate whether these metabolic abnormalities are due to intrinsic skeletal muscle changes, we performed gastrocnemius muscle biopsies on 22 patients with heart failure (peak VO2, 15.4 +/- 4.7 ml/kg/min; ejection fraction, 20 +/- 7%) and on eight normal subjects. Biopsies were analyzed for fiber type and area, capillarity, citrate synthase, phosphofructokinase, lactate dehydrogenase, and beta-hydroxyacyl CoA dehydrogenase activity. All patients with heart failure also underwent 31P NMR studies of their calf muscle during plantarflexion at three workloads. Muscle pH responses and the relation of the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) to systemic VO2 were then evaluated. Compared with normal subjects, patients with heart failure exhibited a shift in fiber distribution with increased percentage of the fast twitch, glycolytic, easily fatigable type IIb fibers (normal subjects, 22.7 +/- 10.1; heart failure, 33.1 +/- 11.1%; p less than 0.05), atrophy of type IIa (normal subjects, 5,477 +/- 1,109; heart failure, 4,239 +/- 1,247 microns 2; p less than 0.05) and type IIb fibers (normal subjects, 5,957 +/- 1,388; heart failure, 4,144 +/- 945 microns 2; p less than 0.01), and decreased activity of beta-hydroxyacyl CoA dehydrogenase (normal subjects, 5.17 +/- 1.44; heart failure, 3.67 +/- 1.68 mol/kg protein/hr; p less than 0.05). No significant linear correlation could be identified between the slope of the Pi/PCr to VO2 relation and muscle histochemistry or enzyme activities. Similarly, no linear relation was found between intracellular pH at peak exercise and any muscle variable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure. 280 70

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

The effect of high-intensity trained (6 X 4.5 min at 40 m/min, 15% grade, 2.5-min rest between bouts, 5 days/wk, for 6 wk) on contractile, biochemical, and fatigue properties of the rat diaphragm were examined. The exercise program produced significant elevations in the mitochondrial marker enzyme citrate synthase (mumol X g-1 X min-1) in the soleus (SOL) (27.2 +/- 1.5 vs. 46.7 +/- 2.4; mean +/- SE), deep vastus lateralis (DVL) (40.8 +/- 2.6 vs. 58.3 +/- 2.8), and superficial vastus lateralis (SVL) (8.5 +/- 0.6 vs. 11.4 +/- 0.7). No significant differences were observed in the crural (CRU) (45.9 +/- 2.0 vs. 44.0 +/- 2.3) or ventral costal (VEN) (41.5 +/- 2.0 vs. 45.8 +/- 2.6) diaphragmatic regions. Phosphofructokinase, the rate-limiting enzyme of glycolysis, significantly increased in the SOL (19.0 +/- 0.8 vs. 23.3 +/- 1.3 mumol X g-1 X min-1) and DVL (69.3 +/- 6.0 vs. 86.6 +/- 5.0), but no alterations were seen in the SVL (98.6 +/- 5.7 vs. 106.1 +/- 9.0), CRU (54.4 +/- 2.8 vs. 53.8 +/- 1.5), or VEN (44.7 +/- 2.4 vs. 46.4 +/- 1.4) posttraining. Diaphragm contractile properties, with the exception of an increased rate of fall in twitch tension, remained unchanged after training. Glycogen values were significantly higher in trained diaphragms at rest (6.54 +/- 0.39 vs. 4.86 +/- 0.41 mg/g) and during 1, 5, and 10 min of fatiguing stimulation. During fatigue no differences were observed in force, rate of rise in force, rate of fall in force, muscle lactate, ATP, or creatine phosphate in trained vs. control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contractile and biochemical properties of diaphragm: effects of exercise training and fatigue. 294 Feb 18

The adaptation of enzyme activities, notably in the oxidative metabolism, and of prerequisites for tissue transport of oxygen in the claudication leg was evaluated by comparing muscle biopsies from the gastrocnemius muscle of the claudication and the symptom-free leg of seven patients with unilateral claudication. The claudication leg had higher activities of a marker enzyme for mitochondrial oxidative capacity, citrate synthase (CS), as well as of the MB and the mitochondrial isoenzyme of creatine kinase (CK), which are considered to be involved in the transfer of high energy phosphate from the mitochondria to the resynthesis of ATP in the cytoplasm. The difference between claudication and healthy leg in activities of these CK isoenzymes were well correlated with the corresponding side difference in CS activity. No significant differences between claudication and healthy leg were found in distribution of muscle fibre types or fibre dimension, capillary density or myoglobin content, nor was there any side difference in phosphofructokinase or lactate dehydrogenase. Side differences tended to be greater in those patients with the most advanced obstructive arterial disease as estimated from non-invasive pressure measurements. It is concluded that in reasonably physically-active patients, the mode of ischaemia to which the claudication leg is subjected leads to a metabolic adaptation characterized by increased activities of enzymes involved in the oxidative metabolism, but no significant adaptation of either the conditions for local oxygen transport, as estimated by myoglobin content, and capillary density, or capacity for anaerobic metabolism.
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PMID:Calf muscle adaptation in intermittent claudication. Side-differences in muscle metabolic characteristics in patients with unilateral arterial disease. 296 71

The effect of hypoxia and post-hypoxic recovery were studied in gastrocnemius muscle of young-adult and mature beagle dogs. Furthermore, the possible interference of pharmacological treatment with nicergoline was evaluated in these conditions. Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose 6-phosphate, pyruvate, lactate), Kreb's cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate) and related free amino acids (glutamate, alanine), ammonium ion, energy store and mediators (ATP, ADP, AMP and creatine phosphate), and the energy charge potential were evaluated. Furthermore, in the crude extract and/or mitochondrial fraction of another portion of the same gastrocnemius muscle the maximum rate (Vmax) of some muscular enzymes related to the anaerobic glycolytic pathway (hexokinase, lactate dehydrogenase), the Kreb's cycle (citrate synthase, malate dehydrogenase), the aminoacid pool related to the Krebs' cycle (glutamate dehydrogenase and aspartate aminotransferase), the electron transfer chain (cytochrome oxidase) and NAD+/NADH exchanges (total NADH cytochrome c reductase) was evaluated. Some glycolytic metabolites and Krebs' cycle intermediates were modified by acute hypoxia, while free amino acids and energy mediators remained practically unchanged. The pharmacological treatment maintained the glucose and succinate muscular concentrations within the normal range, during hypoxia. The behaviour of muscular metabolites during hypoxia and/or post-hypoxic recovery is an age-related event. In fact, only in young-adult animals did the altered values return to normal in post-hypoxic recovery. In the present experimental conditions, only minor changes were observed as far as muscular enzyme activities are concerned. In any case, some enzyme activities tested showed different Vmax in young-adult dogs in comparison with mature ones.
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PMID:Effect of hypoxia, aging and pharmacological treatment on muscular metabolites and enzyme activities. 322 9

Young rats maintained on an iron-deficient diet developed severe anemia and had large decreases in the levels of the iron-containing flavoproteins and cytochromes of the mitochondrial respiratory chain in skeletal muscle. In contrast, the levels of a number of mitochondrial matrix marker enzymes, including citrate synthase, isocitrate dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase, 3-ketoacid-CoA transferase, and aspartate aminotransferase, increased in red skeletal muscle but not in white muscle. Phosphocreatine concentration was decreased and inorganic phosphate concentration was increased in soleus muscle frozen in situ. We hypothesize that the increase in mitochondrial matrix enzymes reflects a stimulus to mitochondrial biogenesis in posture-maintaining and weight-bearing red muscle fibers in severely iron-deficient rats. It is our working hypothesis that this stimulus to mitochondrial biogenesis arises from mild activity of the red fibers and is due to the same perturbation in cellular homeostasis that is normally caused by vigorous exercise or hypoxia. In iron deficiency, the stimulus to mitochondrial biogenesis can induce an increase in only those enzymes not prevented from increasing by iron deficiency, resulting in formation of mitochondria of grossly abnormal composition.
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PMID:Induction of an increase in mitochondrial matrix enzymes in muscle of iron-deficient rats. 347 8

The subcellular distribution of the mitochondrial enzymes lipoamide dehydrogenase (LIPDH), citrate synthase (CS), and beta-hydroxyacyl-CoA-dehydrogenase (HADH) in bovine and porcine liver tissue was studied by measuring the enzyme activities in a phosphate buffer extract of tissue (total activity) and in liver press-juice (cell plasma). In slaughter-fresh liver most of the activity was located in the mitochondria. During storage of liver under refrigeration (+2 degrees C) for several days a large decrease in total LIPDH activity and a lesser decrease in HADH activity, but no change in CS activity were observed. There was no or only little release of the three enzymes into the cell plasma during storage; this indicates that storage of liver at +2 degrees C was not accompanied by a marked damage of mitochondria. Freezing (-20 degrees C) and thawing of bovine and porcine liver caused some losses of the total activity of HADH and particularly of LIPDH but not changes in CS activity. There was a considerable increase in the activities of LIPDH, CS, and HADH in the press juice after freezing and thawing of liver tissue. Apparently freezing of liver results in damage to the mitochondria and, therefore, in a partial release of the three enzymes from the inner membrane of the mitochondrion into the cell plasma. By storage of liver under refrigeration the mitochondria became more sensitive to freezing and thawing. Prolonged frozen-storage of liver resulted in an increased release of LIPDH, CS, and HADH into the cell plasma.
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PMID:[Effect of cold storage and freezing of bovine and porcine liver on activity and subcellular distribution of mitochondrial enzymes]. 359 Sep 94


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