Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamine is utilized at a high rate (fourfold higher than that of glucose) by isolated incubated lymphocytes and produces glutamate, aspartate, lactate and ammonia. The pathway for glutamine metabolism includes the reactions catalysed by glutaminase, aspartate aminotransferase, oxoglutarate dehydrogenase, succinate dehydrogenase, fumarase, malate dehydrogenase and phosphoenolpyruvate carboxykinase. In fact little if any of the carbon of the glutamine that is used is converted to acetyl-CoA for complete oxidation. For this reason, the oxidation of glutamine is only partial and, in an analogous manner to the terminology used to describe the partial oxidation of glucose to lactate as glycolysis, the term glutaminolysis is used to describe the process of partial glutamine oxidation. The role of glutaminolysis in lymphocytes and perhaps other rapidly dividing cells is to provide both nitrogen and carbon for precursors for synthesis of macromolecules (e.g. purines and pyrimidines for DNA and RNA) and also energy. However, the rate of glutamine utilization by lymphocytes is markedly in excess of the precursor requirements (which are at most 4%) and if glutamine was vitally important in energy production it would be expected that more would be converted to acetyl-CoA for complete oxidation via the Krebs cycle. Indeed most of the energy for lymphocytes may be obtained by the complete oxidation of fatty acids and ketone bodies. Consequently the role of the high rate of glutaminolysis in lymphocytes and other rapidly dividing cells may be identical to that of glycolysis: the high rates provide ideal conditions for the precise and sensitive control of the rate of use of the intermediates of these pathways for biosynthesis when required. High rates of glycolysis and glutaminolysis can be seen as part of a mechanism of control to permit synthesis of macromolecules when required without any need for extracellular signals to make more glucose or glutamine available for these cells. In order to maintain a high rate of glutaminolysis despite fluctuation in the plasma level of glutamine, the flux through the glutaminolytic pathway can be controlled and the key processes in the lymphocyte that may play a role in this process include glutamine transport across the cell and mitochondrial membranes, glutaminase and oxoglutarate dehydrogenase. Changes in the intracellular concentration of Ca2+ may play a role in control of one or more of these reactions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Glutamine metabolism in lymphocytes: its biochemical, physiological and clinical importance. 390 97

Cytochemical methods commonly used in hematology were applied to studying the liquor lymphocytes of dogs. According to our observation of decreasing their activity, the enzymes examined are placed in the following order: alpha-glycerophosphate, glutamate, lactate, and succinate dehydrogenase. High and reliable values of asymmetry and excess coefficients show the absence of the normal distribution of enzymatic activity in the investigated population of lymphocytes.
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PMID:[Cytochemical determination of the enzyme activity of cerebrospinal fluid lymphocytes in dogs]. 398 32

1. Mitochondrial and supernatant aspartate transaminases (EC 2.6.1.1) and supernatant alanine transaminase (EC 2.6.1.2) were purified 89-, 204- and 240-fold respectively, from dolphin muscle. Starch-gel electrophoresis of crude and purified preparations revealed that all three enzymes exist as single forms. 2. K(m) values of alpha-oxoglutarate, alanine, pyruvate and glutamate for the alanine transaminase were 0.45, 8.2, 0.87 and 15mm respectively. For the aspartate transaminases, the K(m) values of alpha-oxoglutarate, aspartate, oxalacetate and glutamate were 0.76, 0.50, 0.10 and 9.4mm respectively, for the mitochondrial form and 0.13, 2.4, 0.06 and 3.2mm respectively, for the supernatant form. 3. In all cases, as the assay pH value was decreased from pH7.3, the K(m) values of the alpha-oxo acids decreased whereas those of the amino acids increased. 4. The apparent equilibrium constants for the aspartate transaminases were independent of pH. These values were 9.2 and 6.8 for the mitochondrial and supernatant forms respectively, where [Formula: see text] 5. Studies of the inhibition of the aspartate transaminases by dicarboxylic acids indicated that these enzymes may be controlled by pools of metabolic intermediates. 6. Three key roles are suggested for the transaminases in the energy metabolism of the diving animal. First, it is believed that a combined action of the transaminases could enhance energy production during hypoxia by providing (a) fumarate from aspartate for the ATP-producing reversal of succinate dehydrogenase, and (b) alpha-oxoglutarate from glutamate for the GTP-producing succinyl thiokinase reaction. Secondly, diving mammals probably accumulate more NADH than other mammals during hypoxia. The aspartate transaminases seem particularly well suited for restoring and maintaining redox balance via the malate-aspartate cycle after aerobic metabolism is resumed. Finally, since the preferred fuel for aerobic work is fat, the combined reactions of the transaminases could be instrumental in providing increased supplies of oxaloacetate for sparking the tricarboxylic acid cycle.
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PMID:Purification and properties of dolphin muscle aspartate and alanine transaminases and thier possible roles in the energy metabolism of diving mammals. 446 40

The transport of the tricarboxylic acid cycle C(4)-dicarboxylic acids was studied in both the wild-type strain and tricarboxylic acid cycle mutants of Bacillus subtilis. Active transport of malate, fumarate, and succinate was found to be inducible by these dicarboxylic acids or by precursors to them, whereas glucose or closely related metabolites catabolite-repressed their uptake. l-Malate was found to be the best dicarboxylic acid transport inducer in succinic dehydrogenase, fumarase, and malic dehydrogenase mutants. Succinate and fumarate are accumulated over 100-fold in succinic dehydrogenase and fumarase mutants, respectively, whereas mutants lacking malate dehydrogenase were unable to accumulate significant quantities of the C(4)-dicarboxylic acids. The stereospecificity of this transport system was studied from a comparison of the rates of competitive inhibition of both succinate uptake and efflux in a succinate dehydrogenase mutant by utilizing thirty dicarboxylic acid analogues. The system was specific for the C(4)-dicarboxylic acids of the tricarboxylic acid cycle, neither citrate nor alpha-ketoglutarate were effective competitive inhibitors. Of a wide variety of metabolic inhibitors tested, inhibiors of oxidative phosphorylation and of the formation of proton gradients were the most potent inhibitors of transport. From the kinetics of dicarboxylic acid transport (K(m) approximately 10(-4) M for succinate or fumarate in succinic acid dehydrogenase and fumarase mutants) and from the competitive inhibition studies, it was concluded that an inducible dicarboxylic acid transport system mediates the entry of malate, fumarate, or succinate into B. subtilis. Mutants devoid of alpha-ketoglutarate dehydrogenase were shown to accumulate both alpha-ketoglutarate and glutamate, and these metabolites subsequently inhibited the transport of all the C(4)-dicarboxylic acids, suggesting a regulatory role.
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PMID:Properties of an inducible C 4 -dicarboxylic acid transport system in Bacillus subtilis. 463 50

Acetobacter suboxydans does not contain an active tricarboxylic acid cycle, yet two pathways have been suggested for glutamate synthesis from acetate catalyzed by cell extracts: a partial tricarboxylic acid cycle following an initial condensation of oxalacetate and acetyl coenzyme A. and the citramalate-mesaconate pathway following an initial condensation of pyruvate and acetyl coenzyme A. To determine which pathway functions in growing cells, acetate-1-(14)C was added to a culture growing in minimal medium. After growth had ceased, cells were recovered and fractionated. Radioactive glutamate was isolated from the cellular protein fraction, and the position of the radioactive label was determined. Decarboxylation of the C5 carbon removed 100% of the radioactivity found in the purified glutamate fraction. These experiments establish that growing cells synthesize glutamate via a partial tricarboxylic acid cycle. Aspartate isolated from these hydrolysates was not radioactive, thus providing further evidence for the lack of a complete tricarboxylic acid cycle. When cell extracts were analyzed, activity of all tricarboxylic acid cycle enzymes, except succinate dehydrogenase, was demonstrated.
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PMID:Nonfunctional tricarboxylic acid cycle and the mechanism of glutamate biosynthesis in Acetobacter suboxydans. 464 May 4

The effect of various nutritional conditions on the levels of Krebs cycle enzymes in Bacillus subtilis, B. licheniformis, and Escherichia coli was determined. The addition of glutamate, alpha-ketoglutarate, or compounds capable of being catabolized to glutamate, to a minimal glucose medium resulted in complete repression of aconitase in B. subtilis and B. licheniformis. The synthesis of fumarase, succinic dehydrogenase, malic dehydrogenase, and isocitric dehydrogenase was not repressed by these compounds. It is postulated that glutamate or alpha-ketoglutarate is the true corepressor for the repression of aconitase. A rapidly catabolizable carbon source and alpha-ketoglutarate or glutamate must be simultaneously present for complete repression of the formation of aconitase. Conditions which repress the synthesis of aconitase in B. subtilis restrict the flow of carbon in the sequence of reactions leading to alpha-ketoglutarate but do not prevent glutamate oxidation in vivo. The data indicate that separate and independent mechanisms regulate the activity of the anabolic and catabolic reactions of the Krebs cycle in B. subtilis and B. licheniformis. The addition of glutamate to the minimal glucose medium results in the repression of aconitase, isocitric dehydrogenase, and fumarase, but not malic dehydrogenase in E. coli K-38.
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PMID:Effect of different nutritional conditions on the synthesis of tricarboxylic acid cycle enzymes. 496 Aug 93

Differential rates of incorporation of sugars, organic acids, and amino acids during autotrophic growth of several blue-green algae and thiobacilli have been determined. In obligate autotrophs (both blue-green algae and thiobacilli), exogenously furnished organic compounds make a very small contribution to cellular carbon; acetate, the most readily incorporated compound of those studied, contributes about 10% of newly synthesized cellular carbon. In Thiobacillus intermedius, a facultative chemoautotroph, acetate contributes over 40% of newly synthesized cellular carbon, and succinate and glutamate almost 90%. In the obligate autotrophs, carbon from pyruvate, acetate, and glutamate is incorporated into restricted groups of cellular amino acids, and the patterns of incorporation in all five organisms are essentially identical. These patterns suggest that the tricarboxylic acid cycle is blocked at the level of alpha-ketoglutarate oxidation. Enzymatic analyses confirmed the absence of alpha-ketoglutarate dehydrogenase in the obligate autotrophs, and also revealed that they lacked reduced nicotinamide adenine dinucleotide oxidase, and had extremely low levels of malic and succinic dehydrogenase. These enzymatic deficiencies were not manifested by the two facultative chemoautotrophs examined. On the basis of the data obtained, an interpretation of obligate autotrophy in both physiological and evolutionary terms has been developed.
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PMID:Biochemical basis of obligate autotrophy in blue-green algae and thiobacilli. 496 89

Mutants deficient in sporulation were isolated and characterized with respect to antibiotic and protease activity, transformability, growth, and sporulation. All but two mutants could grow on minimal medium containing glucose. The inability of most mutants to incorporate uracil into trichloroacetic acid-precipitable material (ribonucleic acid) during the developmental period, and their response to a number of carbon sources, were used to characterize their biochemical blocks. Reproducible measurements of these responses were possible when the pH of the culture, which changed during growth and greatly influenced the rate of uracil uptake, was adjusted to 6.5. By their response to ribose and glutamate, the sporulation mutants could then be divided into four groups. All mutants of the first three groups produced antibiotic activity against Staphylococcus aureus, whereas all mutants, except one, of the fourth group produced none or very little of this activity. Mutants which did not respond to glutamate belonged to the first three groups; they also grew slowly or not at all on glutamate as sole carbon source. One of these mutants lacked succinic dehydrogenase activity. The results indicate that most of our sporulation mutants are unable to produce or utilize a natural carbon precursor, which is normally used as a slowly available carbon and energy source via the Krebs cycle when other carbon sources are used up. It enters the Krebs cycle as a precursor of alpha-ketoglutarate, probably via acetylcoenzyme A. All mutants of group four are blocked in this pathway before alpha-ketoglutarate.
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PMID:Analysis of sporulation mutants. I. Response of uracil incorporation to carbon sources, and other mutant properties. 496 68

Sporulation mutants that were unable to incorporate uracil during the developmental period recovered this capacity with the addition of ribose and in most cases with the addition of glutamate. Of the mutants that responded to both ribose and glumate, all but three also responded to citrate, and all but five responded to acetate. One of the exceptional strains was deficient in aconitase and another one in aconitase and isocitrate dehydrogenase; both required glutamate for growth. For the mutants which did not respond to glutamate, the products made from (14)C-glutamate were determined by thin-layer chromatography. Significant differences were found which enabled the identification of mutant blocks. The deficiency of the corresponding enzyme activity was verified. Several mutants were deficient in alpha-ketoglutarate dehydrogenase, and one lacked succinic dehydrogenase. These mutants could still grow on glucose as sole carbon source, but not on glutamate. The intact Krebs cycle is therefore not required for vegetative growth of aerobic Bacillis subtilis, but it is indispensable for sporulation.
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PMID:Analysis of sporulation mutants. II. Mutants blocked in the citric acid cycle. 496 97

The cellular distribution of certain enzymes associated with the metabolic compartmentation of glutamate was estimated in ultrastructurally preserved and metabolically competent perikarya fractions that were enriched in astrocytes, granule cells and Purkinje cells and derived from 8-day-old rat cerebellum, and in monolayer cultures (14 days in vitro) composed principally of interneurones or astrocytes. The neuronal activities of glutamine synthetase and glutamate dehydrogenase were respectively about 4- to 8-fold and 2- to 5-fold lower than in astrocytes, depending upon the class of neurone and the type of preparation used for comparison. By contrast glutaminase activity was about 3- to 12-fold higher in neuronal than in astroglial preparations. Estimations of the specific activity of succinate dehydrogenase differed less between cell types, indicating that the differences in glutamate dehydrogenase and glutaminase were not simply related to variations in the concentration of mitochondria relative to the other cellular constituents. The findings presented provide direct evidence in support of our model assigning the 'small' glutamate compartment, where most of the labelled glutamine is synthesized, to glial cells, and the 'large' compartment to neurones, and also underline the metabolic interaction between these two cell types in the brain.
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PMID:The activities in different neural cell types of certain enzymes associated with the metabolic compartmentation glutamate. 612 8


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