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)

Fifty-seven isolated, blood perfused, continuously weighed canine hearts have been utilized to study the development of abnormal myocardial fluid retention during early myocardial ischemic injury. Inflatable balloon catheters were positioned around the left anterior descending coronary arteries (LAD) of 54 hearts or the proximal left circumflex coronary arteries of three hearts for study of the following intervals of coronary occlusion: a) 10 minutes followed by 20 minutes of reflow, b) 40 minutes followed by either no reflow or by 20 minutes of reflow, and c) 60 minutes without reflow. After 60 minutes of fixed coronary occlusion, histologic and ultrastructural examination revealed mild swelling of many ischemic cardiac muscle cells in the absence of interstitial edema, cardiac weight gain, and obvious structural defects in cell membrane integrity. After 40 minutes of coronary occlusion and 20 minutes of reflow, significant cardiac weight gain occurred in association with characteristic alterations in the ischemic region, including widespread interstitial edema and focal vascular congestion and hemorrhage and swelling of cardiac muscle cells. Focal structural defects in cell membrane integrity were also noted. The development of abnormal myocardial fluid retention after 40 minutes of LAD occlusion occurred in association with a significant reduction in sodium-potassium-ATPase activity in the ischemic area, but with no significant alteration in either creatine phosphokinase or citrate synthase activity in the same region. Despite the abnormal myocardial fluid retention in these hearts, it was possible pharmacologically to vasodilate coronary vessels with adenosine and nitroglycerin infusion to maintain a consistently high coronary flow following release of the coronary occlusion after 40 minutes and to even exceed initial hyperemic flow values following release of the occlusion when adenosine and nitroglycerin infusion was delayed until 15 minutes after reflow. Thus, the data indicate that impaired cell volume regulation and interstitial fluid accumulation and focal structural defects in cell membrane integrity are early manifestations of ischemic injury followed by reflow, but fail to establish a major role for the abnormal fluid retention in altering coronary blood flow prior to the development of extensive myocardial necrosis. In contrast, fixed coronary occlusion for 60 minutes results in mild intracellular swelling but no significant interstitial edema and no obvious structural defects in cell membrane integrity.
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PMID:Abnormal myocardial fluid retention as an early manifestation of ischemic injury. 13 29

1. Percutaneous needle biopsies were obtained from six limb muscles in six horses before and during a training programme of 10 or 15 weeks designed to involve both aerobic and anaerobic work. In a subsequent detraining period, biopsies were also taken after 5 and 10 weeks. 2. Samples were analysed biochemically for enzyme activity of lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aldolase (ALD), citrate synthase (CS), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and for glycogen content. Fibre typing was carried out histochemically before and 10 weeks after commencement of training. 3. There was a significant increase in the percentage of high myosin ATPase activity pH 9-4/high oxidative (FTH) fibres with a corresponding decrease in high myosin ATPase activity pH 9-4/low oxidative (FT) fibres and low myosin ATPase activity pH 9-4/high oxidative (ST) fibres after 10 weeks training. 4. During training, enzyme activities increased progressively but at different rates with an approximate twofold increase in all of the enzymes except CPK by the end of the training period. Changes in all the muscles studied were similar. Glycogen content increased by approximately 33% which was significant when all the muscles were considered together. 5. A decrease in enzyme activity occurred after 5 weeks detraining. However at 10 weeks a consistent but inexplicable increase in all enzyme levels, except CS again occurred. 6. It is concluded that training increased greatly the activity of enzymes involved in both aerobic and anaerobic metabolism.
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PMID:The effect of training and detraining on muscle composition in the horse. 14 28

The activities of phosphofructokinase, pyruvate kinase, citrate synthase and creatine kinase were determined in blastocysts from rabbits at 144 h post coitum and in similar blastocysts cultured for 24 h with or without oestradiol-17beta (1 microgrm/ml). There was a significant increase in all the enzymes during the 24-h culture period but oestradiol had no effect.
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PMID:Regulatory enzymes of carbohydrate and energy metabolism in the rabbit blastocyst. 14 40

Closed aorta working hearts perfused with 1 mM pyruvate were subjected to a 4-fold increase in work load by raising the left atrial filling pressure. Citric acid cycle flux, pyruvate uptake, and oxygen consumption rose 3-fold when cardiac output was increased. In the first 40 sec after the transition tissue glutamate and citrate fell by 22 and 45%, respectively, and there were reciprocal decreases in malate and aspartate. The ratio of creatine phosphate/creatine declined by 50% within 30 sec, with a corresponding increase in inorganic phosphate, but the fall in the ATP/ADP ratio was only 10%. During the first 10 sec the surface fluorescence from cardiac pyridine nucleotides fell by 30% and this change was synchronous with a sharp decline in the calculated adenine nucleotide phosphate potential. This suggests that heart mitochondrial respiration is controlled by the cytosolic phosphate potential, and that a state 4 to state 3 transition occurs when cardiac output is increased. Apparent disequilbrium of creatine phosphokinase can be explained by the compartmentation of most of the cardiac ADP within the mitochondria. Citric acid cycle flux was coordinated by activational interactions at citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, but a transient imbalance between the individual cycle steps leads to a sharp peak of lactate production shortly after the work transition.
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PMID:Regulation of myocardial energy metabolism. 17 15

Thyroxine and cortisone acetate administration of rats of 4--7 days of age is not only accompanied by the induction of the muscle-specific enzyme, creatine kinase, but the hormones also induce morphological changes in the gastrocnemius during this period. Administration of thyroxine to these rats causes a splitting of myofibrils as shown by stereological measurements on electron micrographs. This splitting of myofibrils was not observed upon cortisone acetate administration and when both hormones were given simultaneously. It is suggested that cortisone acetate counteracts the effect of thyroxine. Both thyroxine and cortisone acetate increase the volume percentage taken by the mitochondria at 7 days of age. The effect of the simultaneous injection of both hormones is equal to the sum of the separate effects of these hormones. These changes in volume percentage of the mitochondria were compared with changes in a mitochondrial marker enzyme, i.e. citrate synthase. The difference between the morphological measurements and citrate synthase activity is due to a change in the specific activity of citrate synthase in the mitochondria.
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PMID:Quantitative analysis of morphological changes in skeletal muscle of the rat after hormone administration. 42 Aug 82

The purpose of the present study was to determine the effects of low-frequency electrical stimulation (LFES) on the skeletal muscle metabolic profile of men and women. The knee extensor muscles of sedentary men (N = 16) and women (N = 10) were submitted to 3 h.d-1 of 8-Hz neuromuscular electrical stimulation with the use of a portable stimulator (Respond II, Medtronic), 6 d.wk-1 for 6 wk. Enzyme activity levels of creatine kinase (CK), hexokinase (HK), glyceraldehydephosphate dehydrogenase (GAPDH), 3-hydroxyacyl CoA dehydrogenase (HADH), citrate synthase (CS), phosphofructokinase (PFK), and cytochrome c oxidase (COX) were determined in vastus lateralis muscle samples taken before and after the LFES protocol. The analyses of variance revealed no change in CK and in GAPDH. However, a small decrease in PFK activity, the rate-limiting enzyme of glycolysis, was observed in female (8%) and in male subjects (10%), but it reached significance in males only (P < 0.05). The activity level of HK, a regulatory enzyme of the skeletal muscle glucose phosphorylation (HK), increased significantly in female subjects only (36%; P < 0.01) in response to the stimulation protocol. Activity level of marker enzymes of the Krebs cycle (CS) and of the electron-transfert chain (COX) significantly increased in males (18% and 16%; P < 0.05) as well as in females (31% and 19%; P < 0.05). Increment in the marker enzyme activity of the fatty acid oxidation (HADH) was significant in female subjects (30%; P < 0.01) and, although significant, rather modest in male subjects (12%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electrical stimulation-induced changes in skeletal muscle enzymes of men and women. 133 93

1. Replacement of fetal calf serum and chicken embryo extract by Ultroser G and rat brain extract during the proliferation phase resulted in a higher maturation grade of cultured rat muscle cells after 7 days of differentiation, on base of the percentage of the muscle specific isoenzyme of creatine kinase (CK-MM). 2. Furthermore, the activities of creatine kinase, citrate synthase, cytochrome c oxidase and hexokinase were significantly higher. 3. Compared to the enzyme activities in m. quadriceps of 10 day-old rat and m. quadriceps, m. soleus and m. extensor digitorum longus of young adult rats, the metabolic capacity of cultured myotubes most closely resembles that of the first muscle. 4. Paralysis with tetrodotoxin caused a slight decrease of the creatine kinase activity and the percentage of CK-MM of cultured myotubes and an increase of the activities of hexokinase, phosphorylase and AMP deaminase. 5. Electrical stimulation performed at different frequencies and time periods had no effect on the enzyme activities of cultured rat muscle cells. 6. Only the AMP deaminase activity was decreased after intense electrical stimulation.
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PMID:Effects of growth medium, electrical stimulation and paralysis on various enzyme activities in cultured rat muscle cells. Comparison with activities in rat muscles in vivo. 159 50

On the basis of the percentage creatine kinase-MM, human skeletal muscle cells cultured on growth and differentiation media containing the serum substitute Ultroser G reach a significantly higher maturation grade after 7 days of differentiation than cells cultured on serum-containing media. They also remain viable for longer periods. The myotubes are much longer, their nuclei are often localized in rows on the periphery, and they show cross-striation more frequently. The activities of creatine kinase, citrate synthase, cytochrome c oxidase, AMP deaminase, and phosphorylase are significantly higher. Extending the differentiation period to 3 weeks increases the maturation grade of the cultures and the activities of all the enzymes mentioned before, except phosphorylase. A correlation exists between the enzyme activities and the maturation grade of the muscle cells. The content of fatty acid-binding protein also increases significantly with the maturation grade in contrast to the palmitate oxidation rate. The AMP deaminase and creatine kinase activity and the percentage MM-type remain lower in cultured cells than in adult muscle and the hexokinase activity remains higher, but the other enzyme activities become comparable after 20 days of differentiation. The myotubes, derived from Ultroser G-containing culture media, show spontaneous contractions after 12 days and cross-striation after 20 days when immunostained for the M-subunit of creatine kinase. These cells possess clusters of acetylcholine receptors, but aggregation of desmin at the site of the clusters was never detectable. The possibility of cultivating muscle cells with a predictable maturation grade allows the study of muscle development and muscular diseases caused by differentiation defects or by deficiency of a maturation-dependent (iso)enzyme.
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PMID:The biochemical and structural maturation of human skeletal muscle cells in culture: the effect of the serum substitute Ultroser G. 164 54

Muscle biopsy specimens were obtained from 48 human immunodeficiency virus-infected patients suffering from various neuromuscular symptoms. Microscopic examination by conventional and electron microscopy revealed a characteristic structural myopathy associated with mitochondrial changes in 13 patients, all of whom had received long-term zidovudine therapy. The mean cumulative dose they had received (498 +/- 145 gm) was significantly higher than that of the other 14 zidovudine recipients of the study. They suffered from a progressive, usually painful, proximal myopathy with pronounced wasting, normal-to-moderately elevated creatine kinase levels, and a myopathic electromyographic pattern. The condition usually improved after withdrawal of the drug. Assay of mitochondrial enzymes, including succinate-cytochrome c reductase, cytochrome c oxidase, and citrate synthase, showed a decline in respiratory chain capacity. Southern blot analysis of mitochondrial DNA showed no abnormality. It is likely that mitochondrial dysfunction, probably resulting from drug-induced inhibition of the mitochondrial DNA polymerase, is implicated in the pathogenesis of this complication of zidovudine therapy.
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PMID:Zidovudine myopathy: a distinctive disorder associated with mitochondrial dysfunction. 189 64

Myocardial cytoplasmic creatine kinase subunits M and B, mitochondrial CK (CKMIT), and citrate synthase (CS) were determined in 10 locations of the normal human heart (n = 8) and in papillary muscles of patients operated on for mitral regurgitation (n = 6). Compared to atrial biopsies, septal and left ventricular biopsies showed higher activities for CS (P less than 0.0001), total CK (P less than 0.05) and CKMIT (P less than 0.0001). CKM was evenly distributed. CKB activity in the right septum and left ventricular locations were 0.5-1% of total CK and 4-5 times lower than those of the atria and the right ventricular free wall. Activities of CS, CKB and CKMIT in right septal biopsies did not differ from those in left ventricular locations. The activities of CS, total CK, and CKM in papillary muscle from patients operated on for mitral regurgitation did not differ from that of healthy papillary muscle. CKMIT was about 40% lower (P less than 0.02), whereas CKB was 15-20 times higher (P less than 0.0001) than in the healthy heart. In conclusion, adaptations within the creatine kinase system occur in the human heart in health and disease. Small amounts of CKB in the normal left ventricle, as opposed to the right ventricular free wall, might be related to differences in myocardial perfusion during the cardiac cycle. In disease, a decreased CKMIT and dramatically increased CKB may indicate a stressed intracellular energy transfer. CK enzyme activities in right septal biopsy specimens may be used as an indication of metabolic stress on the myocardium of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dynamics of creatine kinase shuttle enzymes in the human heart. 190 38


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