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)

We previously found that intermittent hyperbaric oxygen exposure increases metabolic enzyme activity in soleus muscle. Since the metabolic enzyme activities of the heart and diaphragm of healthy animals are difficult to alter, we questioned whether intermittent hyperbaric oxygenation would provide a stimulus sufficient to increase metabolic enzyme activity. Therefore, we exposed 36 rabbits (4 groups of 9) twice daily for 90 min 5 days/wk to either 100% O2 at 243 kPa, 8.5% O2, and 91.5% N2 at 243 kPa, 100% O2 at 101 kPa, or 21% O2 at 101 kPa. After 4 wk of treatment, the activities of citrate synthase, succinate dehydrogenase, alpha-glycerophosphate dehydrogenase, phosphofructokinase, and glyceraldehyde-3-phosphate dehydrogenase were measured. In both the heart and the diaphragm, none of the treatments significantly altered the mean enzyme activities for any of the enzymes measured. Therefore, it seems that the hyperbaric oxygenation treatment protocols used do not induce an increase in metabolic enzyme activity in the heart and diaphragm in healthy animals.
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PMID:Hyperbaric oxygenation treatments and metabolic enzymes in the heart and diaphragm. 806 60

It has been suggested that propionyl-L-carnitine administration to ischaemic hearts facilitates the restoration of cardiac function upon reperfusion, but it is still a matter of dispute whether its effect is conveyed via the metabolic effect of the propionyl moiety, the carnitine moiety or other mechanisms involving membrane receptor interactions. The metabolism of propionylcarnitine involves the formation of succinyl-CoA, which causes an increase in the total amount of tricarboxylic acid cycle intermediates. According to the current paradigm, anaplerosis ensures rapid restoration of tricarboxylic acid cycle activity during reperfusion. To evaluate the contribution of anaplerosis to the protective effect of propionylcarnitine during ischaemia and reperfusion, isolated rat hearts were perfused with Krebs-Henseleit bicarbonate buffer containing 5 mM glucose+insulin (12 IU per litre), to which 1 mM propionate, 0.8 mM hexanoate or 1 mM propionylcarnitine were added. Global 20 or 24 min no-flow ischaemia was followed by 10 min reperfusion. The flavoprotein redox state, myoglobin oxygenation, oxygen consumption and mechanical functioning of the heart were recorded and metabolites determined in freeze-trapped tissue. In parallel experiments, the cellular energy state was studied with phosphorus nuclear magnetic resonance spectrometry. The addition of 1 mM propionylcarnitine failed to cause an anaplerotic effect, but did bring about an oxidation of flavins, probably due to citrate synthase inhibition. Propionate showed similar but stronger effects and a marked anaplerosis, but still failed to improve the recovery of the heart upon reperfusion. The addition of hexanoate caused marked anaplerosis upon reperfusion and flavin reduction. The results failed to demonstrate that propionylcarnitine had any beneficial effect on the ischaemic myocardium.
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PMID:Metabolic effects of propionate, hexanoate and propionylcarnitine in normoxia, ischaemia and reperfusion. Does an anaplerotic substrate protect the ischaemic myocardium? 807 Apr 85

During myocardial hypertrophy, histological modifications induce a partial ischemic state and hemodynamic perturbations are responsible for an increased myocardial oxygen demand. The purpose of this study is to better characterize the alterations of intermediary metabolism linked to hemodynamic perturbations by carbon 13 NMR using enriched substrates. Left ventricular hypertrophy was consecutive to a renal hypertension (Goldblatt 2K-1C, 9 weeks). Myocardial compliance and contractility (left ventricular end diastolic pressure (LVEDP), +dP/dt max, +dP/dt max normalized to developed pressure (+dP/dt max/DEVP)) were estimated on Langendorff isolated perfused hearts at a constant perfusion pressure (normo and hypertensive rats (RHR)). Using (2-13C) acetate enriched (10 nm) substrate, 13C NMR spectra were obtained from tissue perchloric extracts. Mathematical model proposed by Malloy was used to analyze these 13C NMR spectra terms of metabolic fluxes: Fc2 = The fraction of (2-13C) acetyl-CoA entering the tricarboxylic acid cycle; y = The ratio between the activity of anaplerotic reactions to that of citrate synthetase. The results showed after hypoxia: an increase of LVEDP more pronounced in RHR (RHR: 48 +/- 15 mmHg VS SHAM: 22 +/- 6 mmHg, p < 0.01); a significant impairment of coronary blood flow more important in RHR; a significant increase of the ratio y in hypertrophied hearts (RHR: 0.062 +/- 0.09 VS SHAM: 0.15 +/- 0.02, p < 0.05). In conclusion, this study allowed a new approach to correlate diastolic dysfunction with metabolic data consecutive to an increased sensitiveness hypertrophy to hypoxic damages.
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PMID:[Metabolic aspects of hemodynamic behavior in left ventricular hypertrophy by 13C NMR]. 812 13

These experiments examined the influence of exercise intensity and duration on antioxidant enzyme activity in locomotor muscles differing in fiber type composition. Nine groups of female Sprague-Dawley rats (age 120 days) exercised 4 days/wk on a motor-driven treadmill for 10 wk. The impact of three levels of exercise intensity (low, moderate, and high: approximately 55, approximately 65, and approximately 75% of maximal oxygen consumption, respectively) and exercise duration (30, 60, and 90 min/day) was assessed. Sedentary animals served as controls. Oxidative capacity in the soleus and white and red gastrocnemius was assessed by measurement of citrate synthase (CS) activity, and antioxidant capacity was evaluated by assay of total superoxide dismutase, catalase, and total glutathione peroxidase (GPX) activities. In all muscles, CS activity increased as a function of exercise duration. Furthermore, in the soleus and white gastrocnemius, the magnitude of the training-induced increase in CS activity was directly related to exercise intensity. In contrast, the peak increase in CS activity in the red gastrocnemius was relatively independent of exercise intensity. Catalase activity was not increased (P > 0.05) in any muscle with training. Training-induced changes in superoxide dismutase and GPX activities were muscle specific; specifically, exercise training significantly (P < 0.05) increased superoxide dismutase activity in the soleus as a function of exercise duration up to 60 min/day. Conversely, training-induced significant (P < 0.05) increases in GPX activity occurred in red gastrocnemius only; the magnitude of the GPX increase was directly related to exercise duration but relatively independent of intensity. These data demonstrate that exercise training-induced changes in muscle antioxidant enzymes are muscle specific.
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PMID:Influence of exercise and fiber type on antioxidant enzyme activity in rat skeletal muscle. 814 92

A low metabolic rate for a given body size and a low fat versus carbohydrate oxidation ratio are known risk factors for body weight gain, but the underlying biological mechanisms are poorly understood. Twenty-four-hour energy expenditure (24EE), sleeping metabolic rate (SMR), 24-hour respiratory quotient (24RQ), and forearm oxygen uptake were compared with respect to the proportion of skeletal muscle fiber types and the enzyme activities of the vastus lateralis in 14 subjects (seven men and seven women aged 30 +/- 6 years [mean +/- SD], 79.1 +/- 17.3 kg, 22% +/- 7% body fat). The following enzymes were chosen to represent the major energy-generating pathways: lactate dehydrogenase (LDH) and phosphofructokinase (PFK) for glycolysis; citrate synthase (CS) and beta-hydroxyacl-coenzyme A dehydrogenase (beta-OAC) for oxidation; and creatine kinase (CK) and adenylokinase (AK) for high-energy phosphate metabolism. Forearm resting oxygen uptake adjusted for muscle size correlated positively with the proportion of fast-twitch muscle fibers (IIa: r = .55, P = .04; IIb: r = .51, P = .06) and inversely with the proportion of slow oxidative fibers (I: r = -.77, P = .001). 24EE and SMR adjusted for differences in fat-free mass, fat mass, sex, and age correlated with PFK activity (r = .56, P = .04 and r = .69, P = .007, respectively). 24RQ correlated negatively with beta-OAC activity (r = -.75, P = .002). Our findings suggest that differences in muscle biochemistry account for part of the interindividual variability in muscle oxygen uptake and whole-body energy metabolism, ie, metabolic rate and substrate oxidation.
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PMID:Whole-body energy metabolism and skeletal muscle biochemical characteristics. 815 8

Vitamin E deficiency in rats gives rise to a neuromuscular syndrome that includes a peripheral neuropathy as well as generalised muscle wasting and weakness. This is probably related to damage by oxygen-derived free radicals. In the present study, histological examination of lower limb muscles showed widespread myopathic changes which included the presence of amorphous electron-dense inclusions and tubular aggregates in muscle fibres and muscle fibre necrosis. Histochemical observations suggested a reduction in the activity of oxidative enzymes. The mitochondria showed nonspecific degenerative changes on electron microscopy; no paracrystalline inclusions were observed. Polarographic analysis of isolated muscle mitochondria revealed statistically significant decreases in oxygen utilisation rates with both NADH and FADH2-linked substrates. In confirmation of a generalised respiratory chain abnormality, enzymatic analyses revealed decreases in the activities of complexes I, II/III and IV, although only the decreases in complexes I and IV activities were statistically significant. Measurements of membrane fluidity showed that this is reduced in mitochondria from vitamin E deficient rats, indicating reduced stability of their membranes. The respiratory control ratio, derived from the polarographic results, was also reduced in mitochondria from vitamin E deficient animals, suggesting membrane damage. An altered lipid environment, possibly secondary to a higher level of lipid peroxidation, could result in the inhibition of complexes I and IV. This could also be caused by oxidative damage to the complexes or to mitochondrial DNA. The preservation of citrate synthase activity is against any generalised defect of mitochondrial function. The question as to whether these defects of mitochondrial respiratory chain function are responsible for the muscle fibre damage and necrosis requires further investigation.
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PMID:Myopathy in vitamin E deficient rats: muscle fibre necrosis associated with disturbances of mitochondrial function. 830 Apr 27

The human leukaemic cell line HL60 undergoes differentiation to granulocyte-like cells in response to dimethylsulphoxide (DMSO). The rates of glucose and glutamine utilization were studied in HL60 cells that were either undifferentiated or fully differentiated by 9 days exposure to DMSO. Differentiation did not alter the rate of utilization of exogenous glucose, approximately 75% of which was converted to lactate in each case. The activities of hexokinase, phosphofructokinase, pyruvate kinase and citrate synthase were similarly unaffected. In contrast, the activity of the oxidative segment of the pentose-phosphate pathway was enhanced by differentiation, and no glycogen synthase activity could be detected. These observations are consistent with the significantly lower content of glycogen, the increased activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and the increased oxidation of [1-14C] glucose relative to [6-14C] glucose in the differentiated cells. Glucose utilization was depressed by exogenous glutamine but, at the same time, glutamine utilization was enhanced by glucose in both cell types; these reciprocal effects were more pronounced in the undifferentiated HL60 cells. Glucose utilization may be depressed in the presence of glutamine as a result of the allosteric inhibition of a rate-limiting step of glycolysis (eg. phosphofructokinase). In spite of having glutaminase activity twice that of their differentiated counterparts, the uptake of glutamine by undifferentiated HL60 cells was low, especially when it was the sole substrate. The stimulation of glutaminolysis by glucose may be due to activation of mitochondrial glutamine transport. A large proportion of the glutamine utilized by both cells contributed to a net accumulation of glutamate, aspartate and alanine, whilst up to 35% was oxidized to CO2. In contrast, almost all of the glucose utilized was converted to lactate and very little was oxidized. The high rates of glycolysis and glutaminolysis observed before and after differentiation may not contribute primarily to energy production but may supply, in undifferentiated cells, substrates for biosynthetic processes that generate nucleic acid precursors or, in the case of differentiated cells which synthesize reactive oxygen intermediates, substrates that maintain NADP in a reduced state.
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PMID:Glycolytic, glutaminolytic and pentose-phosphate pathways in promyelocytic HL60 and DMSO-differentiated HL60 cells. 833 14

This investigation studied the importance of the rise in body temperature during exercise for aerobic capacity adaptations produced by endurance training. The approach used was to compare training effects produced by subjects exercising in hot (35 degrees C) water vs. cold (20 degrees C) water. Hot water was used to potentiate, and cold water to blunt, the rise in body temperature during exercise. Eighteen young men trained by cycle-ergometer exercise at 60% of maximal oxygen uptake (VO2max) while immersed to the neck in either hot (HWT, n = 9) or cold (CWT, n = 9) water for 60 min, 5 days/wk, for 8 wk. Before and after training, VO2max, erythrocyte volume, plasma volume, and vastus lateralis citrate synthase activity were measured. Training increased (P < 0.01) VO2max by 13%, with no difference between HWT and CWT in the magnitude of the effect. Erythrocyte volume increased 4% (P < 0.01) with training, with no difference between HWT and CWT in the magnitude of the effect. Plasma volume remained unchanged by training in both the HWT and CWT groups. Last, vastus lateralis citrate synthase activity increased by 38% with training, but there was no difference between HWT and CWT in the training effect. Thus, exercise-induced body temperature elevations are not an important stimulus for the aerobic adaptations to moderate-intensity endurance training.
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PMID:Role of thermal factors on aerobic capacity improvements with endurance training. 837

Oxygen free radicals have recently been implicated as a major cause of tissue injury in critically ill patients. Glutathione (GSH) is a potent endogenous antioxidant that may be important in minimizing oxidant-induced organ damage. However, this tripeptide is depleted during severe illness. In order to determine the effect of GSH depletion on hepatic high-energy phosphate metabolism, in vivo 31P magnetic resonance spectroscopy was used to measure phosphate ratios in male Wistar rats given 1 ml/kg of diethylmaleate (DEM), an agent that binds and thus depletes tissue GSH, or corn oil vehicle intraperitoneally. Spectra of the liver were obtained in noninjected animals (baseline, n = 15) and in rats 2 and 24 hr after the intraperitoneal injection of DEM (n = 20) or corn oil (control, n = 20). These spectra were used to measure hepatocellular pH, phosphomonoester to ATP (PME/ATP), and phosphodiester to ATP ratios, measures of hepatocellular damage; and the inorganic phosphate (Pi)/ATP ratio, a measure of energy status. In addition, tissue GSH, phosphofructokinase, citrate synthase, and beta-OH-acyl-Co-A dehydrogenase activities as well as hepatocellular ATP were measured in vitro in representative liver samples. Hepatic GSH levels were maximally depressed by 85% 2 hr after the injection of DEM (6.94 +/- 0.34 vs 0.94 +/- 0.22 microM/g wet wt, baseline vs 2 degrees DEM). This was associated with a marked increase in the PME/ATP and Pi/ATP ratios by 25 and 33%, respectively, and both ratios were significantly correlated with the severity of hepatic GSH depletion (r = 0.63, P < 0.001 and r = 0.42, P < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutathione depletion alters hepatocellular high-energy phosphate metabolism. 847 34

To investigate the effect of in vivo heart irradiation on myocardial energy metabolism, we measured myocardial adenosine nucleotide concentrations and mitochondrial oxygen consumption in left ventricular tissue of rats 0-16 months after local heart irradiation (20 Gy). At 24 h and 2 months no difference in myocardial adenosine nucleotide concentration was apparent between irradiated and control hearts. The total myocardial adenosine nucleotide concentrations in irradiated hearts compared to those of nonirradiated controls tended to be lower from 4 months onward. The rate of oxidative energy production (state 3 respiration) in irradiated hearts was significantly reduced compared with that of age-matched controls from 2 months onward. Moreover, as a result of aging, a time-dependent decrease in the rate of oxidative energy production was observed in both irradiated and control hearts (P < 0.001). The respiratory control index (RCI = oxygen consumption in state 3/oxygen consumption in state 4) in irradiated hearts was not different from the RCI measured in age-matched control animals. During the period of study the RCI diminished significantly with age in both groups (P < 0.005). The number of oxygen atoms used per molecule of ADP phosphorylated (P/O ratio) was not influenced by the irradiation. The P/O ratio for the NAD(+)-linked substrates remained unchanged at a value of about 3 during the period studied. At 6 months after irradiation activities of myocardial enzymes such as lactate dehydrogenase, creatine kinase, citrate synthase, and cytochrome c oxidase were reduced. The reduction in myocardial energy production and the changes in energy supplies provide a mechanism to explain impaired contractility after local heart irradiation.
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PMID:Effects of in vivo heart irradiation on myocardial energy metabolism in rats. 847 57


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