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. The present study investigates to what extent increases in resistance to fatigue and aerobic oxidative capacity of energy metabolism are correlated in fast-twitch tibialis anterior muscles of rat and rabbit subjected to chronic low-frequency stimulation. 2. Changes in the aerobic oxidative capacity of the stimulated muscles were judged from increases in citrate synthase activity, representing the constant-proportion enzyme group of the citric acid cycle. 3. Resistance to fatigue reached maximal values in both rat and rabbit tibialis anterior muscles after stimulation periods of 14 days, whereas citrate synthase activity continued to increase with longer stimulation periods. 4. Different time courses of the changes in resistance to fatigue and citrate synthase activity were observed not only with prolonged stimulation periods but also during the first week, when pronounced increases in resistance to fatigue were accompanied by only moderate elevations in citrate synthase activity. 5. The dissociation between the changes of the two parameters studied suggests that factors other than elevated aerobic oxidative capacity contribute to enhanced resistance to fatigue.
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PMID:Asynchronous increases in oxidative capacity and resistance to fatigue of electrostimulated muscles of rat and rabbit. 848 8

Biopsies of the gluteus medius muscle were taken at three different depths from 36 endurance horses aged 8.42 +/- 2.85 years and of both sexes. Twenty of the horses were considered to be excellent performers on the basis of the mean speed of their three fastest records in endurance events over the previous two or three years, whereas 16 were moderate performers. The biopsy samples were analysed for the activities of the enzymes citrate synthase (an indicator of citric acid cycle activity), 3-OH-acyl-CoA-dehydrogenase (an indicator of lipid oxidation) and lactate dehydrogenase (an indicator of anaerobic metabolism). The 20 excellent performers had higher activities of citrate synthase (P < 0.001) and 3-OH-acyl-CoA-dehydrogenase (P < 0.02) than the 16 moderate performers. The activities of citrate synthase and 3-OH-acyl-CoA-dehydrogenase increased by 65 per cent and 75 per cent, respectively, and the activity of lactate dehydrogenase decreased by 23 per cent in the samples taken at successively greater depths. There was a strong linear relationship between the ratios of the activities of lactate dehydrogenase/citrate synthase and lactate dehydrogenase/3-OH-acyl-CoA-dehydrogenase and the depth from which the samples were taken for both performance groups (P < 0.001). The intercepts of the regression lines were higher in the moderate than in the excellent performers (P < 0.001 and P < 0.01 for the two ratios), showing that the endurance horses with the better performance record had a greater aerobic capacity and a relatively lower anaerobic capacity in the gluteus medius muscle than the horses with a poorer record.
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PMID:Activities of selected aerobic and anaerobic enzymes in the gluteus medius muscle of endurance horses with different performance records. 856 Jul 24

Brownian dynamics simulations were performed to investigate a possible role for electrostatic channeling in transferring substrate between two of the enzymes of the citric acid cycle. The diffusion of oxaloacetate from one of the active sites of malate dehydrogenase (MDH) to the active sites of citrate synthase (CS) was simulated in the presence and absence of electrostatic forces using a modeled structure for a MDH-CS fusion protein. In the absence of electrostatic forces, fewer than 1% of substrate molecules leaving the MDH active site are transferred to CS. When electrostatic forces are present at zero ionic strength however, around 45% of substrate molecules are successfully channeled. As expected for an electrostatic mechanism of transfer, increasing the ionic strength in the simulations reduces the calculated transfer efficiency. Even at 150 mM however, the inclusion of electrostatic forces results in an increase in transfer efficiency of more than 1 order of magnitude. The simulations therefore provide evidence for the involvement of electrostatic channeling in guiding substrate transfer between two of the enzymes of the citric acid cycle. Similar effects may operate between other members of the citric acid metabolon.
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PMID:Evidence for electrostatic channeling in a fusion protein of malate dehydrogenase and citrate synthase. 884 Nov 8

The effects of 8 wk of 35 min of aerobic cycle training (3 times/wk) on indexes of male and female human vastus lateralis muscle antioxidant status were investigated. Training resulted in significant elevations in whole body maximal O2 consumption and muscle citrate synthase activity. Despite this, muscle superoxide dismutase, catalase, and glutathione peroxidase activities were not significantly altered by the training protocol. In addition, training did not affect muscle vitamin E (alpha- and gamma-tocopherol) concentrations. Glutathione status determined as the concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), total glutathione (GSH + 2 x GSSG), and GSH/GSSG ratio was unaffected by the training protocol. There were no significant differences between males and females in any indexes of muscle antioxidant status. These results indicate that the moderate aerobic training typically performed by regularly exercising humans did not positively alter endogenous antioxidant status. This suggests that short-term aerobic training increases capacity for flux through the citric acid cycle without necessarily increasing the ability to handle potential free radicals generated by the enhanced electron flux.
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PMID:Lack of antioxidant adaptation to short-term aerobic training in human muscle. 889 71

The effect of physical conditioning on skeletal muscle of individuals with spinal cord injuries (SCI) has been investigated. The anterior portion of the deltoid muscle (active in wheel-chair propulsion) of untrained and endurance-trained paraplegics and tetraplegics, as well as that of untrained able-bodied subjects, was studied. The characterization involved fibre type distribution, capillarization, fibre areas and also oxidative and glycolytic enzyme levels. A general trend towards a successively higher proportion of type I fibres and lower proportion of type IIB fibres was noted in the order of able-bodied subjects (type I, 42%; type IIB, 41%, n = 8), paraplegics (type I, 57%; type IIB, 13%, n = 13) and tetraplegics (type I, 74%; type IIB, 4.5%, n = 11). The trained SCI groups had significantly higher levels of the citric acid cycle marker enzyme citrate synthase (34% and 63%) than the untrained SCI groups and able-bodied subjects, respectively. The glycolytic marker enzyme 6-phosphofructokinase was 32% lower in the tetraplegic groups than in the other groups. In contrast, the fatty acid oxidation marker enzyme 3-hydroxyacyl-CoA dehydrogenase was markedly higher in the tetraplegic group than in the able-bodied subjects (58%) and tended to be higher (21%, P < 0.1) than in the paraplegic group. The trained SCI groups displayed significantly higher (28%) levels of capillaries per fibre than the untrained SCI groups, which had about the same levels as the untrained able-bodied subjects. It is concluded that several of the findings are in line with normal muscular adaptation, whereas others are unexpected and support a hypothesis that some of the findings might be due to differences between the groups in, for instance, hormone levels or in types of muscular load.
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PMID:Skeletal muscle of trained and untrained paraplegics and tetraplegics. 938 47

Anaplerotic enzymes, such as pyruvate carboxylase or malic enzyme, catalyze reactions that fill up the pools of the citric acid cycle (CAC), thereby increasing the total mass of CAC intermediates. Relative anaplerosis (y) denotes the ratio of anaplerotic flux to the flux catalyzed by citrate synthase. We examine conventional methods [C. R. Malloy, A. D. Sherry, and F. M. H. Jeffrey. J. Biol. Chem. 263:6964-6971, 1988; C. R. Malloy, A. D. Sherry, and F. M. H. Jeffrey. Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H987-H995, 1990] of measurement of y using 13C-labeled precursors and analysis of [13C]glutamate labeling by nuclear magnetic resonance (NMR) spectroscopy. Through mathematical analysis and computer simulation, we show that isotopic enrichment of the pool of pyruvate that is substrate for anaplerosis will severely decrease the accuracy of estimates of y made with conventional methods no matter how small the mass of the pool of pyruvate. Suppose that the recycling parameter R denotes the fraction of molecules of pyruvate that contain carbons derived from intermediates of the CAC. Each means of estimation of relative anaplerosis in the peer-reviewed literature assumes that R = O, although this assumption has not been confirmed by experiment. We show that conventional formulas, using either fractional enrichments of carbons or isotopomer analysis, actually estimate at most y.(1 - R) instead of y during administration of [2-13C]acetate and unlabeled pyruvate. Using a new formula for estimation of y, we recalculate values of y from the literature and find them approximately 50% too low. We assume that all anaplerosis is via pyruvate and that the difference in isotopic enrichment between cytosolic and mitochondrial malate is negligible.
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PMID:Improved estimation of anaplerosis in heart using 13C NMR. 943 40

A substrate cycle between citric acid cycle (CAC) intermediates isocitrate and 2-oxoglutarate, involving NAD+- and NADP+-linked isocitrate dehydrogenase (NAD-IDH and NADP-IDH, respectively) and mitochondrial transhydrogenase (H+-Thase), has recently been proposed. This cycle has been hypothesized to enhance mitochondrial respiratory control by increasing the sensitivity of NAD-IDH to its modulators and allowing for enhanced increases in flux through this step of the CAC during periods of increased ATP demand. The activities of the enzymes comprising the substrate cycle: NAD-IDH, forward and reverse NADP-IDH, and forward and reverse H+-Thase, along with the activity of a marker of mitochondrial content, citrate synthase (CS) were measured in mitochondria isolated from rabbit Type I and Type IIb muscles and in whole muscle homogenates, representing the various fiber types, from rats. In isolated rabbit muscle mitochondria, NAD-IDH had significantly higher (1.6 x ) activity in white muscle while forward NADP-IDH, forward and reverse H+-Thase, and CS all had significantly higher (1.2-1.6 x ) activities in red muscle. There was no difference in reverse NADP-IDH between fiber types. Similarly, in rat whole muscle enzyme activities normalized to CS, NAD-IDH had significantly higher activity in fast-twitch glycolytic (FG) fibers, while forward NADP-IDH and forward H+-Thase had significantly higher activities in slow-twitch oxidative (SO) fibers. These results suggest that differences in the activities of the substrate cycle enzymes between skeletal muscle fiber types could contribute to differences in respiratory control due to differential cycling rates and/or loci of control.
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PMID:Fiber-type-related differences in the enzymes of a proposed substrate cycle. 951 25

13C and 1H NMR spectroscopy of plasma glucose was used to resolve the isotopomer contributions from tracer levels of [1,6-13C2]glucose, a novel tracer of glucose carbon skeleton turnover, and [U-13C]propionate, a tracer of hepatic citric acid cycle metabolism. This allowed simultaneous measurements of hepatic glucose production and citric acid cycle fluxes from the NMR analysis of a single plasma glucose sample in fasted animals. Glucose carbon skeleton turnover, as reported by the dilution of [1,6-13C2]glucose, was 56 +/- 2 micromol/kg/min in the presence of labeling from [U-13C]propionate and 53 +/- 4 micromol/kg/min in its absence. Therefore, as expected, the labeling contributions from [U-13C]propionate metabolism did not have a significant effect on the measurement of glucose turnover. For the group infused with both tracers, citric acid cycle flux estimates from the analysis of glucose C2 isotopomer ratios were consistent with those from our recent experiments where only [U-13C]propionate was infused, verifying that the presence of [1,6-13C2]glucose did not interfere with these measurements. This integrated analysis of hepatic glucose output and citric acid cycle fluxes from plasma glucose isotopomers yielded a noninvasive estimate of hepatic citrate synthase flux of 74 +/- 12 micromol/kg/min for 24-h fasted rats.
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PMID:Measurement of hepatic glucose output, krebs cycle, and gluconeogenic fluxes by NMR analysis of a single plasma glucose sample. 975 Jan 40

The maximal activity of a selection of enzymes involved in muscle carbohydrate handling, citric acid cycle and fatty acyl beta-oxidation were studied after treatment with the fluorinated corticosteroid triamcinolone and compared to a similar treatment of the non-fluorinated corticosteroid prednisolone in an equipotent anti-inflammatory dose. Furthermore, because triamcinolone causes loss of body mass and muscle wasting, the effects of triamcinolone were investigated relative to a control group, with the same loss of body mass, due to nutritional deprivation. The study was performed in male Wistar rats in the following treatment groups: TR, triamcinolone treatment (0.25 mg x kg(-1) x day(-1) for 2 weeks), which resulted in a reduction of body mass (24%); ND, nutritional deprivation (30% of normal daily food intake for 2 weeks) resulting in a similar (24%) decrease of body mass as TR; PR, prednisolone treatment (0.31 mg x kg(-1) x day(-1) for 2 weeks), with a 10% increase in body mass; FF, free-fed control group, with a 12% increase in body mass in 2 weeks. Compared to FF, TR induced an increase in phosphofructokinase (PFK) activity (P < 0.01), glycogen synthase [GS(i + d)] activity (P < 0.05) and glycogen content (P < 0.01) in the tibialis anterior muscle. The PR and ND caused no alterations in PFK or citrate synthase (CS) activity compared to FF. Compared to PR, TR induced an increase in PFK (P < 0.01), CS (P < 0.05) and GS(i + d) activity (P < 0.01). Both TR and PR caused an increased muscle glycogen content, being more pronounced in TR (P < 0.05). Compared to ND, TR induced an increased CS (P < 0.05) and GS(i + d) activity (P < 0.01) and glycogen content (P < 0.01). The ND resulted in a decreased glycogen content compared to FF (P < 0.05). None of the treatments affected the activity of glycogen phosphorylase, beta-hydroxyacyl coenzyme A dehydrogenase and lactate dehydrogenase. It was concluded that corticosteroids led to an increased muscle glycogen content; however, the changes in the enzymes of carbohydrate metabolism were corticosteroid type specific and did not relate to undernutrition, which accompanied the triamcinolone treatment.
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PMID:Enzyme activity of rat tibialis anterior muscle differs between treatment with triamcinolone and prednisolone and nutritional deprivation. 1004 33

The glucose-fatty acid cycle of Randle entails two elements: decreased pyruvate dehydrogenase (PDH) activity, which inhibits glucose oxidation, and inhibition of phosphofructokinase (PFK) by a rise in citrate so that glucose-6-phosphate (G-6-P) levels increase, thereby inhibiting hexokinase activity and hence glucose utilization. Chronic exposure of islets to long-chain fatty acids (FA) is reported to lower PDH activity, but the effect on glucose oxidation and glucose-induced insulin secretion is uncertain. We investigated rat islets that were cultured for 4 days with 0.25 mmol/l oleate/5.5 mmol/l glucose. Glucose oxidation was doubled at 2.8 mmol/l glucose and unchanged at 27.7 mmol/l glucose in the FA-cultured islets despite a 35% decrease in assayed PDH activity. Pyruvate content was increased 60%, which may well compensate for the decreased PDH activity and maintain flux through the citric acid cycle. However, a greater diversion of pyruvate metabolism through the pyruvate-malate shuttle is suggested by unchanged pyruvate carboxylase Vmax and a fourfold higher release of malate from isolated mitochondria. The FA-cultured islets also showed increased basal glucose usage and insulin secretion together with a lowered level of G-6-P and 50% reductions in citrate synthase Vmax and the citrate content. Thus, the effects of chronic FA exposure on islet glucose metabolism differ from the glucose-fatty acid interactions reported in some other tissues.
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PMID:Glucose-fatty acid cycle to inhibit glucose utilization and oxidation is not operative in fatty acid-cultured islets. 1048 Jun 4


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