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)

1. Activities of a glycolytic enzyme--lactate dehydrogenase, LDH, and two oxidative enzymes--citrate synthase (CS), a marker for TCA cycle entry, and 3-hydroxyacyl-CoA dehydrogenase (HAD), which indicates the capacity for beta-oxidation of endogenous lipids, were measured in fast (tibialis anterior, TA, and extensor digitorum longus, EDL) and slow (soleus, SOL) muscles of Sprague-Dawley rats with intact and limited blood supply, and following treatment with the xanthine derivative torbafylline (Hoechst, Werk Albert, Wiesbaden). 2. Limitation of blood supply by unilateral ligation of the common iliac artery increased activity of LDH in fast muscles, and activity of CS and HAD in soleus. 3. Torbafylline treatment caused an increased LDH activity in intact fast muscles and decreased it in soleus, although the relative capacity for anaerobic and aerobic metabolism (indicated by the ratio of LDH and CS activities) remained unchanged in all cases. 4. Whilst having little effect on oxidative enzyme activity of fast muscles, torbafylline decreased the activity of CS but increased activity of HAD in soleus, suggesting a greater reliance on lipid metabolism. 5. The effect of arterial ligation on enzyme activity was ameliorated by treatment with torbafylline, possibly due to its effect on the microcirculation.
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PMID:The effect of torbafylline on enzyme activities in fast and slow muscles with limited blood supply. 167 66

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

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

Tibialis anterior (TA) muscle of mouse, rat, guinea pig, and rabbit was indirectly stimulated for 10 h/day at 10 Hz up to 28 days. Changes in the activity levels of hexokinase (HK), phosphofructokinase (PFK), glyceraldehydephosphate dehydrogenase (GAPDH), lactate dehydrogenase (LDH), creatine kinase (CK), citrate synthase (CS), malate dehydrogenase (MDH), 3-hydroxyacyl-CoA dehydrogenase (HADH), and beta-hydroxybutyrate dehydrogenase (HBDH) were compared. Although the direction of changes in the enzyme activity pattern was in accordance with previous findings on rabbit TA, the magnitude of the responses varied markedly between the mammals under study. Mouse TA was almost unaffected. A major effect of chronic stimulation in rat, guinea pig and rabbit was an increase in enzyme activities of aerobic-oxidative metabolism. According to intrinsic differences of the muscles under study, the increases varied among the species and appeared to be inversely related to the basal levels of these enzymes in the unstimulated muscles. Conversely, glycolytic enzyme activities (PFK, GAPDH, LDH) markedly decreased in rat, guinea pig, and rabbit, and were only slightly reduced in mouse. Changes in HK and HBDH activities displayed the largest variations in the induced change between species. These results indicate species-specific patterns of metabolic adaptation to increased contractile activity.
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PMID:Species-specific effects of chronic nerve stimulation upon tibialis anterior muscle in mouse, rat, guinea pig, and rabbit. 317 88

Thirty-six biopsy specimens of human biceps and vastus lateralis muscles were examined by histometric analysis and determination of enzyme activities (phosphorylase, triosephosphate dehydrogenase, 3-hydroxacyl-CoA-dehydrogenase, lactate dehydrogenase, hexose isomerase, citrate synthetase, 6-phosphogluconate dehydrogenase). The series included 13 specimens from patients suffering from a benign form of muscular dystrophy (limb girdle and Becker type of muscular dystrophy) and 12 specimens from patients with an acute (n = 5) or chronic (n = 7) form of myositis. Muscle fibres were atrophic in myositis and hypertrophic (with an increased variation of fibre diameters) in muscular dystrophies, as has been shown previously. When myositis samples were compared with either normal or dystrophic muscles, a highly significant lowering of glycolytic enzyme activity was found in chronic myositis, while the activity of 6-phosphogluconate dehydrogenase was elevated to highly significant levels. Measurements of the latter enzyme's activity might be of additional value in differentiating chronic forms of myositis from benign muscular dystrophies.
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PMID:Additional biochemical criteria in the differential diagnosis of myositis. 343 Jan 87

Eighteen male and 20 female patients who underwent reconstruction of their anterior cruciate ligament (ACL) with a flap from the patellar tendon were randomly assigned into either closed cast, isometric muscle training and electric stimulation (ES group), or closed cast and isometric training alone (control group). The degree of quadriceps wasting was determined from computerized tomographic scans (CT) before and 6 weeks after surgery. Electrical stimulation was given with a battery operated stimulator that produced a rectangular asymmetric balanced biphasic pulse shape. The pulse rate was 40 Hz and the pulse width 300 microseconds. Patients received 30 min of stimulation three times daily during 5.5 weeks. Female control patients showed a larger decrease in quadriceps area on CT than male control patients (P less than .001). No significant difference was found between male electrically stimulated patients and control patients. In female patients, there was on the contrary, a highly significant difference in favor of electrical stimulation (P less than .001) When the different parts of the quadriceps were studied, a significantly lower degree of atrophy of the vastus medialis was found after electrical stimulation. Vastus lateralis did not show any difference. Measurements of CT attenuation, pre- and post-operatively, showed a decrease in attenuation of 17% for the vastus medialis and lateralis of the operated leg after immobilization, indicating an increase in fat content. In the rectus femoris, however, there was an increase in attenuation of 14.6%. Percutaneous muscle biopsies from the vastus lateralis obtained before, one week after, and 6 weeks after surgery revealed that the cross-sectional area of the individual muscle fibers decreased less in the electrically stimulated than in controls, but the difference was not significant. There were no differences between the two groups in the activity of an oxidative enzyme, citrate synthase, or a glycolytic enzyme, phosphofructokinase (PFK). We conclude that females reacted more favorably than males to electrical stimulation of quadriceps during an immobilization period after knee surgery.
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PMID:Prevention of quadriceps wasting after immobilization: an evaluation of the effect of electrical stimulation. 349 82

The levels of hexokinase, as well as those of the cytoplasmic glycolytic enzyme lactate dehydrogenase and the mitochondrial tricarboxylic acid cycle enzymes fumarase and citrate synthase, have been determined in whole rat brain and in neuronal, astrocytic, and oligodendroglial fractions isolated from rat brain. Compared with either whole brain or with isolated neurons or astrocytes, oligodendroglia are low in hexokinase content. This provides direct confirmation for the conclusion, based on an electron microscopic immunohistochemical method, that oligodendroglia, compared with other neural structures, contain relatively low levels of this key enzyme of glucose metabolism. Based on this confirmation, it is concluded that the electron-microscopic immunohistochemical procedure provides a valid indication of hexokinase content, and thus that other structures shown to stain weakly by the latter technique (e.g., dendritic terminals of cerebellar granule and Purkinje cells) are, indeed, low in hexokinase activity.
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PMID:Relative levels of hexokinase in isolated neuronal, astrocytic, and oligodendroglial fractions from rat brain. 683 50

1. The differentiation of myotomal muscles in the brook trout (Salvelinus fontinalis Mitchill) has been investigated using p-phenylene diamine stained semi-thin sections and cytochemical and quantitative determinations of enzyme activities. 2. Evidence is presented that the range of fibre size in white muscle represents stages in growth rather than distinct fibre types. 3. Electromyography shows that both red and white muscles are recruited for sustained swimming. The threshold swimming speed for recruitment of white fibres is around 1.8 body length/s (L/s). 4. White muscle citrate synthetase and cytochorome oxidase activities are 25-35% that of red muscle. Hexokinase, phosphorylase and phosphofructokinase activities are 2, 4 and 2 times higher in white than red muscles. It is considered that the aerobic capacity of white muscle is sufficient to support sustained swimming, and that blood glucose could be an important fuel source. 5. Endurance exercise training has been investigated in fish swimming, continuously, for 21 days at 3 L/s. This training regime restricts spontaneous high-speed swimming activity and resulted in a general decline of white muscle glycolytic enzyme activities. Red fibres underwent hypertrophy relative to non-exercised controls (530 +/- 64 microns2 non-exercised, 901 +/- 63 microns2 trained). Aerobic enzyme activities in red muscle and the fraction of fibre volume occupied by mitochondria (30.2 +/- 0.8%) did not change in response to the training programme, but glycolytic enzyme activities were elevated. 3-OH Acyl CoA dehydrogenase activities increased in both red and white muscles indicating an enhanced capacity for fatty acid catabolism with training. 6. Plasma and muscle lactate levels were not statistically different between tank-rested and trained fish swimming a 3 L/s. 7. Adaptations of fish muscle to endurance training are discussed and compared with results for other vertebrates.
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PMID:Exercise training in skeletal muscle of brook trout (Salvelinus fontinalis). 742 13

Enzyme activities of the energy supplying metabolism were investigated in muscle specimens of brachial biceps, deltoid or anterior tibial muscles of patients with traumatic nerve lesions, polyneuropathies, Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, spinal muscular atrophy and hemiparesis. The key enzymes of glycogenolysis (glycogen phosphorylase), glycolysis (triosephosphate dehydrogenase, lactate dehydrogenase), alpha-glycerophosphate cycle (alpha-glycerophosphate dehydrogenase), beta-oxidation of fatty acids (beta-hydroxy-acyl-CoA-dehydrogenase), citrate acid cycle (citrate synthase, malate dehydrogenase), hexokinase reaction (hexokinase) and pentosephosphate shunt (6-phosphogluconate dehydrogenase) were measured. The present study shows that in case of disorders of the lower motor neuron--especially those with impaired axoplasmic transport--changes in the enzyme patterns of muscles occur at an early stage. The glycolytic enzyme activities are of particular significance because they are the most sensitive indicators of the onset, extent and course of neurogenic atrophy. There is a good correlation between severity of the lesion, functional state of the muscles and reduction of these enzyme activities. In case of traumatic nerve lesions re-innervation can prevent a permanent reduction of glycolytic enzymes only if it occurs during the first months after denervation. In all cases in which operative revision is considered, it is therefore not advisible to wait since the regenerative capacity of the motor neuron is not the only limiting factor but also the biochemical and morphological changes in the muscle fibre. These are permanent after long lasting denervation without re-innervation within the first months. Primary neuroaxonal degeneration of the nerve fibre which was found in the majority of our alcoholic patients obviously impairs the metabolism of the muscle to a greater extent than primary demyelination most frequently observed in diabetics with polyneuropathy. Corresponding to the chronic course of the illness over years and to the severity of the pareses, drastic reduction in the activities of glycolytic enzymes was found in patients with Charcot-Marie-Tooth disease. Simultaneously the activity of 6-phosphogluconate dehydrogenase was significantly increased as a result of the chronic neurogenic lesion of the muscle fibres. Follow-up during the treatment of diseases of the lower motor neuron can be performed because the enzyme activities can be measured even in small muscle specimens. In patients with hemiparesis slight but not significant reduction in the glycolytic enzyme activities was found by comparison with a normal control group. We assume that this reduction is due to general inactivity which is caused by the movement disorder rather than to the particular influence of the upper motor neuron.
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PMID:[Biochemical studies on muscles in neurogenic atrophies and central paralysis. Studies of the trophic functions of neurons]. 742 10

Pharyngeal muscles play important roles in the maintenance of upper airway patency during sleep. The present study determined the extent of heterogeneity among pharyngeal muscles and the diaphragm in their metabolic profiles, and examined whether differences among muscles may account for previously described differences in their fatigue resistance. Cat and rat sternohyoid, geniohyoid, genioglossus (cat only) and diaphragm muscle were assayed for activities of the mitochondrial enzyme citrate synthase (CS), the glycolytic enzyme phosphofructokinase (PFK) and the cytosolic enzyme lactate dehydrogenase (LDH). CS activity varied among muscles in both species, being highest for genioglossus in cat and highest for diaphragm in rat. PFK activity was highest for genioglossus in cat, but did not differ among muscles in rat. LDH activity was lower for the genioglossus than the sternohyoid and diaphragm in cat. CS and PFK activities correlated positively, and LDH activity correlated negatively, with in vitro fatigue resistance assessed after 5 min of repetitive stimulation in cat. These data indicate close relationships between metabolic profiles, particularly oxidative capacity, and fatigue resistance of pharyngeal muscles in relationship to each other and to the diaphragm.
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PMID:Metabolic profiles of cat and rat pharyngeal and diaphragm muscles. 893 Nov 76


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