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)

Post-translational modification of mitochondrial proteins by phosphorylation or dephosphorylation plays an essential role in numerous cell signaling pathways involved in regulating energy metabolism and in mitochondrion-induced apoptosis. Here we present a phosphoproteomic screen of the mitochondrial matrix proteins and begin to establish the protein phosphorylations acutely associated with calcium ions (Ca(2+)) signaling in porcine heart mitochondria. Forty-five phosphorylated proteins were detected by gel electrophoresis-mass spectrometry of Pro-Q Diamond staining, while many more Pro-Q Diamond-stained proteins evaded mass spectrometry detection. Time-dependent (32)P incorporation in intact mitochondria confirmed the extensive matrix protein phosphoryation and revealed the dynamic nature of this process. Classes of proteins that were detected included all of the mitochondrial respiratory chain complexes, as well as enzymes involved in intermediary metabolism, such as pyruvate dehydrogenase (PDH), citrate synthase, and acyl-CoA dehydrogenases. These data demonstrate that the phosphoproteome of the mitochondrial matrix is extensive and dynamic. Ca(2+) has previously been shown to activate various dehydrogenases, promote the generation of reactive oxygen species (ROS), and initiate apoptosis via cytochrome c release. To evaluate the Ca(2+) signaling network, the effects of a Ca(2+) challenge sufficient to release cytochrome c were evaluated on the mitochondrial phosphoproteome. Novel Ca(2+)-induced dephosphorylation was observed in manganese superoxide dismutase (MnSOD) as well as the previously characterized PDH. A Ca(2+) dose-dependent dephosphorylation of MnSOD was associated with an approximately 2-fold maximum increase in activity; neither the dephosphorylation nor activity changes were induced by ROS production in the absence of Ca(2+). These data demonstrate the use of a phosphoproteome screen in determining mitochondrial signaling pathways and reveal new pathways for Ca(2+) modification of mitochondrial function at the level of MnSOD.
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PMID:Mitochondrial matrix phosphoproteome: effect of extra mitochondrial calcium. 1648 45

The enzymatic capacity for metabolism of poly-(beta)-hydroxybutyrate (PHB) has been examined in nitrogen-fixing symbioses of soybean (Glycine max L.) plants, which may accumulate substantial amounts of PHB, and chickpea (Cicer arietinum L.) plants, which contain little or no PHB. In the free-living state, both Bradyrhizobium japonicum CB 1809 and Rhizobium sp. (Cicer) CC 1192, which form nodules on soybean and chickpea plants, respectively, produced substantial amounts of PHB. To obtain information on why chickpea bacteroids do not accumulate PHB, the specific activities of enzymes of PHB metabolism (3-ketothiolase, acetoacetyl-coenzyme A reductase, PHB depolymerase, and 3-hydroxybutyrate dehydrogenase), the tricarboxylic acid cycle (malate dehydrogenase, citrate synthase, and isocitrate dehydrogenase), and related reactions (malic enzyme, pyruvate dehydrogenase, and glutamate:2-oxoglutarate transaminase) were compared in extracts from chickpea and soybean bacteroids and the respective free-living bacteria. Significant differences were noted between soybean and chickpea bacteroids and between the bacteroid and free-living forms of Rhizobium sp. (Cicer) CC 1192, with respect to the capacity for some of these reactions. It is suggested that a greater potential for oxidizing malate to oxaloacetate in chickpea bacteroids may be a factor that favors the utilization of acetyl-coenzyme A in the tricarboxylic acid cycle over PHB synthesis.
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PMID:Enzymes of Poly-(beta)-Hydroxybutyrate Metabolism in Soybean and Chickpea Bacteroids. 1653 45

In order to investigate the relationship between malate oxidation and subsequent cycle reactions, the effects of oxaloacetate, pyruvate, and thiamine pyrophosphate on malate oxidation in mung bean (Phaseolus aureus var. Jumbo) hypocotyl mitochondria were quantitatively examined. Malate oxidation was optimally stimulated by addition of pyruvate and thiamine pyrophosphate, whose addition lowered the apparent Km for malate from 5 mm to 0.1 mm. Intermediate analysis showed that the stimulatory effect was correlated with removal of oxaloacetate to citrate. Oxaloacetate added alone was shown not to be metabolized until addition of pyruvate and thiamine pyrophosphate; then oxaloacetate was converted in part to pyruvate and also to citrate. These results establish that malate oxidation in mung bean mitochondria is subject to control by oxaloacetate levels, which are primarily determined by the resultant of the activities of malate dehydrogenase, citrate synthase, and pyruvate dehydrogenase.
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PMID:Regulation of malate oxidation in isolated mung bean mitochondria: I. Effects of oxaloacetate, pyruvate, and thiamine pyrophosphate. 1665 93

Nuclear magnetic resonance spectroscopy was utilized to study the metabolism of [1-(13)C]glucose in mycelia of the ectomycorrhizal ascomycete Sphaerosporella brunnea. The main purpose was to assess the biochemical pathways for the assimilation of glucose and to identify the compounds accumulated during glucose assimilation. The majority of the (13)C label was incorporated into mannitol, while glycogen, trehalose and free amino acids were labeled to a much lesser extent. The high enrichment of the C1/C6 position of mannitol indicated that the polyol was formed via a direct route from absorbed glucose. Randomization of the (13)C label was observed to occur in glucose and trehalose leading to the accumulation of [1,6-(13)C]trehalose and [1,6-(13)C]glucose. This suggests that the majority of the glucose carbon used to form trehalose was cycled through the metabolically active mannitol pool. The proportion of label entering the free amino acids represented 38% of the soluble (13)C after 6 hours of continuous glucose labeling. Therefore, amino acid biosynthesis is an important sink of assimilated carbon. Carbon-13 was incorporated into [3-(13)C]alanine and [2-(13)C]-, [3-(13)C]-, and [4-(13)C]glutamate and glutamine. From the analysis of the intramolecular (13)C enrichment of these amino acids, it is concluded that [3-(13)C]pyruvate, arising from [1-(13)C]glucose catabolism, was used by alanine aminotransferase, pyruvate dehydrogenase, and pyruvate carboxylase (or phosphoenolpyruvate carboxykinase). Intramolecular (13)C labeling patterns of glutamate and glutamine were similar and are consistent with the operation of the Krebs cycle. There is strong evidence for (a) randomization of the label on C2 and C3 positions of oxaloacetate via malate dehydrogenase and fumarase, and (b) the dual biosynthetic and respiratory role of the citrate synthase, aconitase, and isocitrate dehydrogenase reactions. The high flux of carbon through the carboxylation (presumably pyruvate carboxylase) step indicates that CO(2) fixation is an important component of the carbon metabolism in S. brunnea, and it is likely that this anaplerotic role is particularly prevalent during NH(4) (+) assimilation. The most relevant information resulting from this investigation is (a) the occurrence of the mannitol cycle, (b) a large part of the trehalose pool is synthesized after the cycling of glucose-carbon through the mannitol cycle, and (c) pyruvate (or phosphoenolpyruvate) carboxylation plays an important role in the primary metabolism of glucose-fed mycelia.
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PMID:Carbohydrate and Amino Acid Metabolism in the Ectomycorrhizal Ascomycete Sphaerosporella brunnea during Glucose Utilization : A C NMR Study. 1666 12

Dry and Wiskich ([1987] Arch Biochem Biophys 257: 92-99) have published data showing the response of plant mitochondrial respiration to increasing additions of oxaloacetate or malate when these substrates have been depleted by inhibition of succinate dehydrogenase by malonate, and coenzyme A (CoA) has been sequestered as acetyl-CoA by pyruvate dehydrogenase. In the presence of 2-oxoglutarate, it is shown that the response is given by a Michaelis-Menten curve, but in its absence, when malate has to supply substrate for dehydrogenation as well as to liberate CoA via malate dehydrogenase and citrate synthase, the response is presumably the product of two Michaelis-Menten functions, which can be approximated by the square of a single function.
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PMID:A squared michaelis-menten function of substrate concentration for plant mitochondrial respiration. 1666 57

1. Alterations in myocardial energy metabolism accompany pressure overload-induced hypertrophy. We previously described a novel model of catecholamine-induced hypertrophy in which A/J mice exhibit more robust cardiac hypertrophy than B6 mice. Accordingly, we assessed the influence of mouse strain on the activities of key myocardial metabolic enzymes and whether there are strain-related metabolic adaptations to short-term, high-dose isoproterenol (ISO) administration. 2. Thirty-nine male mice (19 A/J mice, 20 B6 mice), aged 12-15 weeks, were randomly assigned to receive either ISO (100 mg/kg, s.c.) or vehicle (sterile water) daily for 5 days. On Day 6, all hearts were excised, weighed, freeze clamped and assayed for pyruvate dehydrogenase (PDH), medium chain acyl-CoA dehydrogenase, carnitine palmitoyl transferase I and citrate synthase activities. Plasma fatty acids (FA) were also measured. 3. The ISO-treated A/J mice demonstrated greater percentage increases in gravimetric heart weight/bodyweight ratio than ISO-treated B6 mice (24 vs 3%, respectively; P < 0.001). All enzyme activities were significantly greater in vehicle-treated B6 mice than in A/J mice, illustrating a greater capacity for aerobic metabolism in B6 mice. Administration of ISO reduced PDHa (active form) activity in B6 mice by 47% (P < 0.001), with no significant change seen in A/J mice. Free FA levels were not significantly different between groups; thus, the differences in PDHa were not due to changes in FA. 4. The basal activity of myocardial metabolic enzymes is greater in B6 mice than in A/J mice and ISO alters myocardial PDH activity in a mouse strain-dependent manner. Compared with A/J mice, B6 mice demonstrate less ISO-induced cardiac hypertrophy, but greater activity of key enzymes regulating FA and carbohydrate oxidation, which may protect against the development of hypertrophy. The metabolic adaptations associated with ISO-induced hypertrophy differ from those reported with pressure overload hypertrophy.
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PMID:Mouse strain-specific differences in cardiac metabolic enzyme activities observed in a model of isoproterenol-induced cardiac hypertrophy. 1720 39

Different values exist for glucose metabolism in white matter; it appears higher when measured as accumulation of 2-deoxyglucose than when measured as formation of glutamate from isotopically labeled glucose, possibly because the two methods reflect glycolytic and tricarboxylic acid (TCA) cycle activities, respectively. We compared glycolytic and TCA cycle activity in rat white structures (corpus callosum, fimbria, and optic nerve) to activities in parietal cortex, which has a tight glycolytic-oxidative coupling. White structures had an uptake of [(3)H]2-deoxyglucose in vivo and activities of hexokinase, glucose-6-phosphate isomerase, and lactate dehydrogenase that were 40-50% of values in parietal cortex. In contrast, formation of aspartate from [U-(14)C]glucose in awake rats (which reflects the passage of (14)C through the whole TCA cycle) and activities of pyruvate dehydrogenase, citrate synthase, alpha-ketoglutarate dehydrogenase, and fumarase in white structures were 10-23% of cortical values, optic nerve showing the lowest values. The data suggest a higher glycolytic than oxidative metabolism in white matter, possibly leading to surplus formation of pyruvate or lactate. Phosphoglucomutase activity, which interconverts glucose-6-phosphate and glucose-1-phosphate, was similar in white structures and parietal cortex ( approximately 3 nmol/mg tissue/min), in spite of the lower glucose uptake in the former, suggesting that a larger fraction of glucose is converted into glucose-1-phosphate in white than in gray matter. However, the white matter glycogen synthase level was only 20-40% of that in cortex, suggesting that not all glucose-1-phosphate is destined for glycogen formation.
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PMID:Evidence for a higher glycolytic than oxidative metabolic activity in white matter of rat brain. 1731 1

Aluminum (Al), an environmental toxin, is known to have a negative impact on various biological systems. However, some microbes have devised intricate mechanisms to combat the toxic influence of this trivalent metal. In this study, Pseudomonas fluorescens grown in malate invoked a unique metabolic shift to promote the synthesis of citrate, a metabolite involved in the sequestration of Al. Electrophoretic and spectrophotometric assays revealed several malate-metabolizing enzymes including malate dehydrogenase (MDH) and malic enzyme (ME) displayed increases in activity and expression in the Al-treated cells. Whereas pyruvate dehydrogenase (PDH) also showed increased activity and expression in the Al-stressed cultures, phosphoenolpyruvate carboxykinase (PEPCK) displayed a marked diminution in the Al-treated cells. The upregulation of citrate synthase (CS) coupled with the diminished activities of aconitase (ACN) and NAD-isocitrate dehydrogenase (NAD-ICDH) appeared to be instrumental in the accumulation of citrate. HPLC experiments revealed high levels of citrate in the Al-stressed cultures. Thus, an Al-enriched environment provoked a metabolic shift in P. fluorescens dedicated to the conversion of malate to citrate.
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PMID:A novel metabolic network leads to enhanced citrate biogenesis in Pseudomonas fluorescens exposed to aluminum toxicity. 1833 65

High-intensity aerobic interval training (HIIT) is a compromise between time-consuming moderate-intensity training and sprint-interval training requiring all-out efforts. However, there are few data regarding the ability of HIIT to increase the capacities of fat and carbohydrate oxidation in skeletal muscle. Using untrained recreationally active individuals, we investigated skeletal muscle and whole-body metabolic adaptations that occurred following 6 weeks of HIIT (~1 h of 10 x 4 min intervals at ~90% of peak oxygen consumption (VO2 peak), separated by 2 min rest, 3 d.week-1). A VO2 peak test, a test to exhaustion (TE) at 90% of pre-training VO2 peak, and a 1 h cycle at 60% of pre-training VO2 peak were performed pre- and post-HIIT. Muscle biopsies were sampled during the TE at rest, after 5 min, and at exhaustion. Training power output increased by 21%, and VO2 peak increased by 9% following HIIT. Muscle adaptations at rest included the following: (i) increased cytochrome c oxidase IV content (18%) and maximal activities of the mitochondrial enzymes citrate synthase (26%), beta-hydroxyacyl-CoA dehydrogenase (29%), aspartate-amino transferase (26%), and pyruvate dehydrogenase (PDH; 21%); (ii) increased FAT/CD36, FABPpm, GLUT 4, and MCT 1 and 4 transport proteins (14%-30%); and (iii) increased glycogen content (59%). Major adaptations during exercise included the following: (i) reduced glycogenolysis, lactate accumulation, and substrate phosphorylation (0-5 min of TE); (ii) unchanged PDH activation (carbohydrate oxidation; 0-5 min of TE); (iii) ~2-fold greater time during the TE; and (iv) increased fat oxidation at 60% of pre-training VO2 peak. This study demonstrated that 18 h of repeated high-intensity exercise sessions over 6 weeks (3 d.week-1) is a powerful method to increase whole-body and skeletal muscle capacities to oxidize fat and carbohydrate in previously untrained individuals.
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PMID:High-intensity aerobic interval training increases fat and carbohydrate metabolic capacities in human skeletal muscle. 1908 69

Lake Baikal is rich in endemic sponge species, among them the arborescently growing species Lubomirskia baicalensis. During winter when the lake is covered by ice, this species reproduces sexually, reflecting a high metabolic activity. Throughout the year, L. baicalensis lives in association with dinoflagellates, which - according to the data presented herein - are symbiotic. The dinoflagellates have been determined on the basis of their rDNA/ITS characteristics and were found to display high sequence similarity to Gymnodinium sanguineum. The dinoflagellates give the sponge its characteristic green color, reflecting the high chlorophyll content (chlorophyll-a content in March and September of 3.2 +/- 0.6 microg/g and 1.9 +/- 0.5 microg/g of protein, respectively). With the in vitro cell culture system for sponges, the primmorphs, it could be demonstrated that [(14)C] glycerol is readily taken up by sponge cells; this process can be inhibited by phloretin, an aquaporin channel blocker. In order to prove the effect of cholesterol on the intermediate metabolism of the sponge cells, molecule probes, cDNAs for key enzymes in gluconeogenesis, glycolysis, and citric acid, have been applied in Northern blot studies. The data revealed that the genes coding for the enzymes citrate synthase and fructose-1,6-bisphosphatase are strongly upregulated after exposure of primmorphs to glycerol. This effect is abolished by phloretin. The genes encoding the phosphoglucose isomerase and pyruvate dehydrogenase do not respond to glycerol supply, suggesting that their expression is not under genetic control in L. baicalensis. To prove the assumption that the aquaporin channel is involved in the influx of glycerol in sponge cells, this cDNA was cloned and applied for in situ hybridization studies. The results obtained show that cells surrounding the dinoflagellates become brightly stained after hybridization with the aquaporin this probe. This demonstrates that L. baicalensis cells respond to glycerol, a metabolite which might be supplied by the dinoflagellates and imported via the aquaporin channel into the sponge cells.
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PMID:Symbiotic interaction between dinoflagellates and the demosponge Lubomirskia baicalensis: aquaporin-mediated glycerol transport. 1919 76


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