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)

In a 29-year-old patient suffering from exertional muscle intolerance with a ubiquinol-cytochrome c reductase deficiency related to a cytochrome b gene point mutation of the mitochondrial DNA, we conducted a study of the aims of which were: (1) to test whether changes in the maximum activities of muscle key enzymes of the main energy-producing pathways occur, (2) to address the issue of whether fibers of different types are equally affected in their enzymatic machinery involved in energy production, and (3) to correlate the results obtained with histochemical and 31P NMR spectroscopy data. When compared to results obtained in six normal subjects, our study clearly shows that the type I fibers of the patient virtually all contained subsarcolemmal mitochondrial aggregates and increased activities of succinate dehydrogenase and cytochrome c oxidase; microdissected type I fibers also displayed a significant increase in both citrate synthase and beta-hydroxyacyl-CoA dehydrogenase, two key enzymes of mitochondrial oxidative metabolism. Despite these changes in the patient's muscle, its whole energy-producing machinery remained impaired as revealed by a slowed post-exercise recovery of phosphocreatine.
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PMID:Increase in oxidative key enzymes in a case of muscle ubiquinol-cytochrome c reductase deficiency. 919 98

To elucidate the reasons for glycolytic deviation commonly found in brain tumors, hexokinase (HK) activity, mitochondria-HK binding, oxidative phosphorylation and mitochondrial ultrastructure were studied in 4 human xenografted gliomas. Lactate/pyruvate ratios were increased 3-4 fold and HK activity was of 2-4 fold lower than that of normal rat brain tissue, used as the control. The mitochondria-bound HK (mHK) fraction varied considerably and represented 9 to 69% of the total HK of that normal rat brain. The respiratory activity of glioma mitochondria, assessed by polarography and spectrophotometry, was within the normal range. However, the mitochondrial content of gliomas was lower than in the rat brain tissue, as revealed by the markedly decreased, activities of two unrelated mitochondrial enzymes, cytochrome c oxidase and citrate synthase in glioma homogenates. Electron microscopical studies confirmed the reduced number of mitochondria in 3 out of the 4 gliomas. Profound alterations of mitochondrial ultrastructure, namely of cristae and matrix densities, were observed in the 4 gliomas. The intercrista space was wider in all gliomas and the crista area was larger in 3 out of the 4 gliomas than in normal rat brain. Finally, the outer membrane of glioma mitochondria interacted intimately and extensively with the rough endoplasmic reticulum (RER) and/or nuclear membrane. These results suggest that, because of the very low content of normally functioning mitochondria, gliomas shift their energy metabolism towards a high-level glycolysis to generate their cellular ATP supply, probably through RER-mitochondria interactions and transformation-dependent redistribution of particulate HK from non-mitochondrial to mitochondrial receptors.
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PMID:Gliomas are driven by glycolysis: putative roles of hexokinase, oxidative phosphorylation and mitochondrial ultrastructure. 921 43

There is increasing evidence that a defect of the mitochondrial respiratory chain is implicated in the development of Parkinson disease. Decreased complex I activity of the mitochondrial respiratory chain has been reported in platelets, muscle, and brain of patients with Parkinson disease. Extrapyramidal symptoms (e.g. parkinsonism and dystonic reactions) are major limiting side effects of neuroleptics. Experimental evidence suggests that neuroleptics inhibit complex I in rat brain. There has not been a study of the effects of neuroleptics in human tissue, however. We therefore analyzed the activities of complexes I + III, complexes II + III, succinate dehydrogenase, complex IV (cytochrome c oxidase), and of citrate synthase in normal human brain cortex after the addition of haloperidol and chlorpromazine and the atypical neuroleptics risperidone, zotepine, and clozapine. Activity of complex I was progressively inhibited by all neuroleptics. Half-maximal inhibition (IC50) was 0.1 mM for haloperidol, 0.4 mM for chlorpromazine, and 0.5 mM for risperidone and zotepine. Clozapine had no effect on enzyme activity at concentrations up to 0.5 mM, followed by a slow decline with a maximum inhibition of 70% at 10 mM. IC50 was at about 2.5 mM. Thus, the concentration of clozapine needed to cause 50% inhibition of the activity of complexes I and III was about 5 times that of zotepine and risperidone, about 6 times that of chlorpromazine, and 25 times that of haloperidol. The inhibition thus paralleled the incidence of extrapyramidal effects caused by the different neuroleptics as they are known from numerous clinical studies. Our data support the hypothesis that neuroleptic-induced extrapyramidal side effects may be due to inhibition of the mitochondrial respiratory chain.
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PMID:Inhibition of complex I by neuroleptics in normal human brain cortex parallels the extrapyramidal toxicity of neuroleptics. 930 97

The activity of glycolytic and oxidative enzymes was monitored in the white muscle of Atlantic cod Gadus morhua experiencing different growth rates. A strong positive relationship between the activity of two glycolytic enzymes and individual growth rate was observed regardless of whether the enzyme activity was expressed as units per gram wet mass, units per gram dry mass or with respect to muscle protein and DNA content. The most sensitive response to growth rate was observed when pyruvate kinase and lactate dehydrogenase activities were expressed as units per microgram DNA, and this may be useful as an indicator of growth rate in wild fish. In contrast, no relationship between the activities of oxidative enzymes and growth rate was observed when cytochrome c oxidase and citrate synthase activities were expressed as units per gram protein. Apparently, the aerobic capacity of white muscle in cod is not specifically increased to match growth rate.
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PMID:How should enzyme activities be used in fish growth studies? 931 92

Treatment with the combination of almitrine-raubasine increases both arterial oxygen partial pressure and haemoglobin oxygen saturation, reflecting an actual increase in the oxygen content of arterial blood. Furthermore, at the trans-cerebral carotid artery/internal jugular vein level, the treatment increases cerebral arterio-venous oxygen and glucose differences, suggesting an actual increase both in oxygen and glucose availability and uptake in cerebral tissues. The increased glucose transfer to the brain is supported also by enhancement of the 3H-deoxyglucose uptake induced by drug pre-treatment both in normoxia and hypoxia. Both almitrine and raubasine act at cerebral mitochondrial levels by decreasing the 'loss' of the 'biological' free energy for phosphorylation supported by the age-related drop in the cerebral enzyme activities, such as phosphofructokinase, pyruvate dehydrogenase and citrate synthase. Furthermore, the components interfere with the alterations induced by peroxidative stress acting at the level of cytochrome c, cytochrome c oxidase and succinate dehydrogenase. Treatment with the combination almitrine-raubasine increases the concentration of noradrenaline metabolites, while alteration of the dopaminergic system is less important. The interference with the noradrenergic system is possibly linked to the electroencephalographic changes induced by drug treatment: increasing alpha-rhythm distribution and reactivity, and increases in beta-rhythm amplitude. Pharmacological effects of almitrine-raubasine, obtained in experimental conditions, correlate with clinical therapeutic efficacy, e.g., in the treatment of cognitive disorders associated with ageing and other cerebral and neurosensory impairments. It is difficult to summarise, in a few pages, the large number of papers related to the cerebral pharmacometabolic and pharmacodynamic activities of the almitrine-raubasine combination. Thus, this review presents in sequential steps some of the interrelated research in humans and laboratory animals which describes in a critical way preclinical to clinical results.
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PMID:Pharmacological features of an almitrine-raubasine combination. Activity at cerebral levels. 951 73

Little information is presently available concerning mitochondrial respiratory and oxidative phosphorylation function in the normal human heart during growth and development. We investigated the levels of specific mitochondrial enzyme activities and content during cardiac growth and development from the early neonatal period (10-20 days) to adulthood (67 years). Biochemical analysis of enzyme specific activities and content and mitochondrial DNA (mtDNA) copy number was performed with left ventricular tissues derived from 30 control individuals. The levels of cytochrome c oxidase (COX) and complex V specific activity, mtDNA copy number and COX subunit II content remained unchanged in contrast to increased citrate synthase (CS) activity and content. The developmental increase in CS activity paralleled increasing CS polypeptide content, but was neither related to overall increases in mitochondrial number nor coordinately regulated with mitochondrial respiratory enzyme activities. Our findings of unchanged levels of cardiac mitochondrial respiratory enzyme activity during the progression from early childhood to older adult contrasts with the age-specific regulation found with CS, a Krebs cycle mitochondrial enzyme.
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PMID:Human mitochondrial function during cardiac growth and development. 954 45

We report automated methods for assaying the activities of the mitochondrial respiratory chain enzyme cytochrome c oxidase (COX), the matrix enzyme citrate synthase (CS), and the cytoplasmic enzyme lactate dehydrogenase (LDH) on a random access analyzer, the Roche Mira S. COX activity was assayed by measuring the initial rate of oxidation of reduced cytochrome c. The CS assay was based on the reaction of this enzyme with oxaloacetate and acetyl-CoA to produce CoASH, which further reacts with dithionitrobenzoic acid producing a free thionitrobenzoate ion. LDH activity was assayed by measuring the reduction of nicotinamide adenine dinucleotide during the oxidation of lactate to pyruvate. Precision of the COX assay was 2. 3%, CS assay 0.7%, and LDH 5.6%. These automated methods were faster by as much as 80%, cheaper by 50%, and used less than half the sample material needed for traditional manual methods. While these assays are often performed by specialized laboratories using dedicated staff, the automated methods presented here are easily performed by staff trained in the regular diagnostic laboratory.
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PMID:Automated analysis of mitochondrial enzymes in cultured skin fibroblasts. 961 94

The activities of the enzymes NADH dehydrogenase, NADH cytochrome e reductase, succinate dehydrogenase, succinate cytochrome e reductase, cytochrome c oxidase and citrate synthase in normal and sick human skeletal muscle mitochondria were determined. A control group was formed by 13 normal people and without using continuous medication. The patient group was formed by 10 people whose pathological diagnosis indicated suspicion of mitochondrial myopathy. A decrease in the activity of the enzymes in all patient was observed: 7 with abnormality in all the tested enzymes; 2 with deficiencies in all the enzymes except cytochrome e oxidase; and 1 with dysfunction only in the activities of succinate dehydrogenase and succinate cytochrome e reductase. The results indicate multiple or combined deficiencies in the respiratory chain, besides dysfunction of citrate synthase in 9 patients. In one exceptional case, the enzymatic deficiency was restricted to complex II. It is possible to conclude that the methodology used herein is adequate and easily applicable to clinical objectives, and that the results obtained allow characterization of the deficient mitochondrial enzymatic complexes, thus showing that the origin of the diseases is an energetic metabolic dysfunction.
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PMID:[Characterization of mitochondrial myopathies through the evaluation of the enzymatic activities involved in energy metabolism]. 962 85

Ultrastructural analysis typically shows vertebrate striated muscles to possess mitochondria residing primarily in two locations. One population is interlaced throughout the myofibrils and another occurs directly beneath the cell membrane. The two populations of mitochondria can be separated and studied in vitro. Subsarcolemmal mitochondria (SSmt) are released by mechanical shearing of the tissue, whereas protease treatment is required to release the intermyofibrillar population (IMFmt). These methods were applied to rainbow trout (Oncorhynchus mykiss) red muscle to investigate the possible existence of distinct populations in this tissue. The two populations were very similar in mitochondrial DNA content (mtDNA mg-1 mitochondrial protein) and enzymatically (activities of carnitine palmitoyl transferase, &bgr ;-hydroxyacyl CoA dehydrogenase, complex I, citrate synthase, cytochrome c oxidase expressed per milligram of mitochondrial protein). Respiration rates were the same for pyruvate and succinate, but IMFmt oxidized palmitoyl carnitine 26 % faster than SSmt (P<0.05). Apart from these minor differences in fatty acyl carnitine oxidation rates, no differences in biochemical or genetic properties were detected between populations. The lack of distinct subcellular populations in fish, in contrast to the situation in mammalian striated muscle, probably relates to the high mitochondrial volume density in fish red muscle.
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PMID:Are there distinct subcellular populations of mitochondria in rainbow trout red muscle? 967 7

The purpose of this research is to determine possible causes and mechanisms involved in the age-associated decline in mitochondrial activity. We have focused on cytochrome c oxidase because it is comprised of both nuclear and mitochondrial-encoded subunits and may provide some insight into the coordination of the two genomes. In agreement with previous reports, we show an approximate 30% decrease in cardiac cytochrome c oxidase activity at 24 months compared to 6 months with no change in the activity of the nuclear encoded citrate synthase of the mitochondrial matrix. The rate of the mitochondrial protein synthesis as shown by [35S]methionine incorporation decreased approximately 35% in the 24-month-old rat compared to the 6-month-old rat. The decrease in protein synthesis was associated with a 30-50% reduction in the levels of most individually radiolabeled translation products including the COX subunits and specifically, a 23% decrease in COX1 protein steady-state levels according to Western analysis. Similarly, there was a decrease in the mRNA steady-state levels of both nuclear and mitochondrial-encoded subunits of cytochrome c oxidase. These results suggest that a number of different mechanisms are involved in the age-associated decrease in heart mitochondrial activity and these are discussed.
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PMID:Age-associated changes in mitochondrial mRNA expression and translation in the Wistar rat heart. 970 70


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