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)

The effect of prolonged digoxin treatment (1 mg/kg day for 8 days) on the activity levels of some enzymes of energy metabolism (phosphofructokinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase) in rat myocardium was studied. In the control animals receiving the solvent mixture (glycerol:ethanol:water in 1:1:1) a transient decrease in the lactate dehydrogenase and citrate synthase activity levels was observed. In the hearts of digoxin treated rats the level of activity of phosphofructokinase was permanently lowered by the fourth day and the level of activity of citrate synthase permanently increased after the first day of treatment. A transient increase in the activity level of succinate dehydrogenase in the myocardium of digoxin treated animals was seen between days 1 and 6. In this study a permanent decrease in phosphofructokinase and an increase in citrate synthase activity levels in rat heart muscle was noted during prolonged digoxin treatment.
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PMID:Enzyme activities of myocardial energy metabolism during prolonged digoxin treatment in rats. 14 96

In isolated hepatocytes from normal fed rats, the subcellular distribution of malate, citrate, 2-oxoglutarate, glutamate, aspartate, oxaloacetate, acetyl-CoA and CoASH has been determined by a modified digitonin method. Incubation with various substrates (lactate, pyruvate, alanine, oleate, oleate plus lactate, ethanol and aspartate) markedly changed the total cellular amounts of metabolites, but their distribution between the cytosolic and mitochondrial compartments was kept fairly constant. In the presence of lactate, pyruvate or alanine, about 90% of cellular aspartate, malate and oxaloacetate, and 50% of citrate was located in the cytosol. The changes in acetyl-CoA in the cytosol were opposite to those in the mitochondrial space, the sum of both remaining nearly constant. The mitochondrial acetyl-CoA/CoASH ratio ranged from 0.3-0.9 and was positively correlated with the rate of ketone body formation. The mitochondrial/cytosolic (m/c) concentration gradients for malate, citrate, 2-oxoglutarate, glutamate, aspartate, oxaloacetate, acetyl-CoA and CoASH averaged from hepatocytes under different substrate conditions were determined to be 1.0, 8.8, 1.6, 2.2, 0.5, 0.7, 13 and 40, respectively. From the distribution of citrate, a pH difference of 0.3 across the inner mitochondrial membrane was calculated, yet lower values resulted from the m/c gradients of 2-oxoglutarate, glutamate and malate. The mass action ratios for citrate synthase and mitochondrial aspartate aminotransferase have been calculated from the metabolite concentrations measured in the mitochondrial pellet fraction. A comparison with the respective equilibrium constants indicates that in intact hepatocytes, neither enzyme maintains its reactants at equilibrium. On the assumption that mitochondrial malate dehydrogenase and 3-hydroxybutyrate dehydrogenase operate near equilibrium, the concentration of free oxaloacetate appears to be 0.3-2 micron, depending on the substrate used. Plotting the calculated free mitochondrial oxaloacetate concentration against the citrate concentration measured in the mitochondrial pellet yielded a hyperbolic saturation curve, from which an apparent Km of citrate synthase for oxaloacetate in the intact cells of 2 micron can be derived, which is comparable to the value determined with purified rat liver citrate synthase. The results are discussed with respect to the supply of substrates and effectors of anion carriers and of key enzymes of the tricarboxylic acid cycle and fatty acid biosynthesis.
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PMID:Distribution of metabolites between the cytosolic and mitochondrial compartments of hepatocytes isolated from fed rats. 68 Jun 39

The malate synthase activity detectable in crude extracts of Pseudomonas AM1 has been shown to be due to a coupling of a malyl-CoA hydrolase with malyl-CoA lyase and not due to a discrete malate synthase enzyme. The partial purification of this malyl-CoA hydrolase from Pseudomonas AM1 has shown that it is distinct from citrate synthase which also hydrolyses malyl-CoA. The malyl-CoA hydrolase has a low Km for malyl-CoA (7-0 muM). A mutant of Pseudomonas AM1, ICT51 (Taylor & Anthony, 1975), which is unable to grow on ethanol, malonate or 3-hydroxybutyrate, has been shown to have an altered malyl-CoA hydrolase with a Km for malyl-CoA 30 times higher than that of the enzyme present in the wild-type organism. Two classes of revertants to growth on these substrates have been isolated: (i) those with a malyl-CoA hydrolase of similar Km to the wild-type and (ii) those in which the malyl-CoA hydrolase activity remains the same as in the mutant ICT51. The nature of the mutation leading to the latter class of revertants is unknown.
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PMID:Synthesis and hydrolysis of malyl-coenzyme A by Pseudomonas AM1: an apparent malate synthase activity. 95 73

Addition of benzoate to the medium reservoir of glucose-limited chemostat cultures of Saccharomyces cerevisiae CBS 8066 growing at a dilution rate (D) of 0.10 h-1 resulted in a decrease in the biomass yield, and an increase in the specific oxygen uptake rate (qO2) from 2.5 to as high as 19.5 mmol g-1 h-1. Above a critical concentration, the presence of benzoate led to alcoholic fermentation and a reduction in qO2 to 13 mmol g-1 h-1. The stimulatory effect of benzoate on respiration was dependent on the dilution rate: at high dilution rates respiration was not enhanced by benzoate. Cells could only gradually adapt to growth in the presence of benzoate: a pulse of benzoate given directly to the culture resulted in wash-out. As the presence of benzoate in cultures growing at low dilution rates resulted in large changes in the catabolic glucose flux, it was of interest to study the effect of benzoate on the residual glucose concentration in the fermenter as well as on the level of some selected enzymes. At D = 0.10 h-1, the residual glucose concentration increased proportionally with increasing benzoate concentration. This suggests that modulation of the glucose flux mainly occurs via a change in the extracellular glucose concentration rather than by synthesis of an additional amount of carriers. Also various intracellular enzyme levels were not positively correlated with the rate of respiration. A notable exception was citrate synthase: its level increased with increasing respiration rate. Growth of S. cerevisiae in ethanol-limited cultures in the presence of benzoate also led to very high qO2 levels of 19-21 mmol g-1 h-1. During growth on glucose as well as on ethanol, the presence of benzoate coincided with an increase in the mitochondrial volume up to one quarter of the total cellular volume. Also with the Crabtree-negative yeasts Candida utilis, Kluyveromyces marxianus and Hansenula polymorpha, growth in the presence of benzoate resulted in an increase in qO2 and, at high concentrations of benzoate, in aerobic fermentation. In contrast to S. cerevisiae, the highest qO2 of these yeasts when growing at D = 0.10 h-1 in the presence of benzoate was equal to, or lower than the qO2 attainable at mu(max) without benzoate. Enzyme activities that were repressed by glucose in S. cerevisiae also declined in K. marxianus when the glucose flux was increased by the presence of benzoate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of benzoic acid on metabolic fluxes in yeasts: a continuous-culture study on the regulation of respiration and alcoholic fermentation. 152 84

We propose an experimental approach combining 1H-NMR and 13C-NMR spectroscopy to investigate metabolite flux in cells under physiological conditions and present a mathematical model giving the relationships between the following different parameters. 13C fractional enrichment, fluxes in competing pathways, metabolite concentration and experimental time. This model has been used for determining the absolute and/or relative values of five fluxes involving pyruvate, ethanol, acetyl-CoA and glutamate via the Krebs cycle in glucose-grown repressed Saccharomyces cerevisiae cells fed with [1-13C]glucose and/or unlabeled ethanol. The glucose consumption and the production of various compounds such as ethanol, glycerol, trehalose etc. were studied qualitatively and/or quantitatively as a function of time. The 13C fractional enrichment of [2-13C]ethanol was determined by observing the proton resonance of the methyl group. Addition of 25 mM unlabeled ethanol shows no significant effect on the glucose consumption or the production of any metabolites. However unlabeled ethanol exerts a strong influence on the enrichment of glutamate C4, but only induces an insignificant change on glutamate C2 and C3. Apart from the fact that ethanol is a potential precursor of acetyl-CoA as expected, these results indicate that (a) the probability for citrate and 2-oxoglutarate to make one turn or more in the Krebs cycle is negligible and (b) the scrambling between C4 and C3 via the glyoxylate shunt is virtually absent. The flux of ethanol formation from pyruvate is about three-times and nine-times greater than that of ethanol consumption and acetyl-CoA formation, respectively, from pyruvate via pyruvate dehydrogenase. Without addition of unlabeled ethanol, the ratio of the integrated resonance of glutamate (C2 + C3)/C4 reflecting the activity of pyruvate carboxylase relative to that of citrate synthase, is about 1.1. By comparing the absolute values of the different fluxes, it was found that 88% of the glucose was used to synthetize ethanol but the observed concentration of ethanol in the supernatant represents only 58% of the glucose consumption. The validity of the present model was supported by the data obtained from similar experiments using unlabeled ethanol and non-NMR techniques.
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PMID:Determination of flux through different metabolite pathways in Saccharomyces cerevisiae by 1H-NMR and 13C-NMR spectroscopy. 168 49

A new approach is proposed to investigate the metabolic perturbation induced by drugs in cells. The effects of various concentrations of amphotericin B on the aerobic [1-13C]glucose metabolism in glucose-grown repressed Saccharomyces cerevisiae cells were studied as a function of time using 13C-, 1H-NMR and biochemical methods. The 13C enrichment of different compounds such as ethanol, glycerol and trehalose were determined by 1H-NMR spectroscopy. In the absence of amphotericin B, glycerol diffuses slowly from the internal to the external medium, whereas in its presence this diffusion is greatly facilitated by the formation of pores in the cell membrane. Amphotericin B has been found to exert a marked influence on the glucose consumption and the production of all metabolites; for example, at 1 microM, the glucose consumption and the production of ethanol decrease while the production of glycerol and trehalose increases. The 13C relative enrichments of ethanol, glycerol and trehalose are almost the same with and without the drug. Thus it can be concluded that amphotericin B induces a large effect on the production of these compounds in the cytosol but shows no significant influence on the mechanism of their formation. Upon addition of glucose, all the amino acid concentrations decrease continuously with time; this effect is more pronounced in the presence of the drug. The ratio of the integrated resonances of glutamate (C2 + C3)/C4 reflects the activity of pyruvate carboxylase relative to citrate synthase rather than to pyruvate dehydrogenase. Without amphotericin B, this ratio (approximately 1.0) is practically constant upon addition of glucose which suggests that the activities of pyruvate carboxylase and citrate synthase are equivalent. By contrast, upon coaddition of 25 mM glucose and 1 microM amphotericin B, the glutamate C4 resonance remains virtually unchanged while that of glutamate C2 is much smaller than in its absence and continuously decreases with time. It seems likely that amphotericin B induces a reduction in the activity of pyruvate carboxylase in the mitochondria.
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PMID:Effects of amphotericin B on the glucose metabolism in Saccharomyces cerevisiae cells. Studies by 13C-, 1H-NMR and biochemical methods. 201 23

Considered are our own data and those found in literature on the properties of yeast mutants impaired in their ability to utilize methanol as sole carbon and energy source; hypotheses about the role of alcohol oxidase and citrate synthase in biogenesis of peroxisomes are proposed. It has been proved that formaldehyde reductase participates in the control of the formaldehyde level in the cell. Properties of mutants defective in the catabolite repression and inactivation of enzymes of methanol metabolism are described. The existence of several autonomous mechanisms of the catabolite repression of alcohol oxidase has been shown. It has been found, that the induction of glyoxysomal enzymes of C2-metabolism is repressed by methanol in the ecr1 mutant of Pichia pinus with the affected repression of alcohol oxidase by ethanol. Data are presented on the regulatory properties of the recently discovered acidification system of the medium induced by methanol. Such acidification occurs due to symport extrusion of protons and formate anions from the cells.
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PMID:Genetic control of methanol utilization in yeasts. 306 50

Some key enzyme activities from the energy metabolism of A. pullulans have been studied during the ethanol-induced yeast-to-mycelium transition. Both the mycelial and yeast-like forms showed greater glucose-6-phosphate dehydrogenase activity than phosphofructokinase. During the morphological transition, the most outstanding variations occurred in large cells (3 days), especially for citrate synthase, malate dehydrogenase and isocitrate lyase activities. However, similar variations were detected in cultures without glucose or ethanol, which showed no morphological transition. Therefore, the observed changes in the enzymatic activities may be attributed to the absence of glucose. As this is not sufficient to induce the morphological transition, we conclude that there is no evidence of a clear-cut relationship between morphology and the activity of the enzymes studied.
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PMID:[Evolution of several enzyme activities of Aureobasidium pullulans during the transition from yeast to mycelium induced by ethanol]. 326 91

Acetate derived from ethanol oxidation is activated by cytosolic and mitochondrial acetyl-CoA synthetases before contributing to the extra-mitochondrial processes of fatty acid and 3-beta-hydroxysterol synthesis. Mitochondrially-generated acetyl-CoA is transferred to the cytosol via citrate and ATP-citrate lyase; this transfer is blocked by (-)-hydroxycitrate. Rats were injected IV with 3.3 mmol/kg of [2-3H,2-14C] acetate and IP with either 0.5 mmol/kg hydroxycitrate or saline. After one hour, the rats were killed and the incorporation of label was measured in liver fatty acids and 3-beta-hydroxysterols. The 3H/14C ratio was increased by 12 and 13% in the fatty acids and 3-beta-hydroxysterols of the hydroxycitrate-treated group. The lower ratio in the fatty acids and 3-beta-hydroxysterols derived from mitochondrially-generated acetyl-CoA is ascribed to a loss of 3H in the citrate synthase reaction. The data showed that (1) fatty acids and 3-beta-hydroxysterols syntheses use the same pool of cytosolic acetyl-CoA; and (2) in the absence of an isotope effect in the citrate synthase reaction, mitochondrially-generated acetyl-CoA contributes about 36% to lipogenesis from acetate.
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PMID:Contributions of cytosolic and mitochondrial acetyl-CoA syntheses to the activation of lipogenic acetate in rat liver. 610 97

Cells of the aerotolerant anaerobe Giardia lamblia respire in the presence of oxygen. Endogenous respiration is stimulated by glucose but not by other carbohydrates and Krebs cycle intermediates. Endogenous and glucose-stimulated respiration are insensitive to cyanide, malonate, and 2,4-dinitrophenol, but are inhibited by atabrin and iodoacetamide. G. lamblia produces ethanol, acetate and CO2 both aerobically and anaerobically either from endogenous reserves or exogenous glucose. Molecular hydrogen is not produced. The following enzyme activities were detected in homogenates: hexokinase, fructose-biphosphate aldolase, pyruvate kinase, phosphoenolpyruvate carboxykinase, malate dehydrogenase, malate dehydrogenase (decarboxylating), pyruvate synthase, acetyl-CoA synthetase, alcohol dehydrogenase (NADP+), NADH dehydrogenase, NADPH dehydrogenase, NADPH oxidoreductase and superoxide dismutase. The enzymes of energy and carbohydrate metabolism are nonsedimentable (109 000 x g for 30 min). Activities of lactate dehydrogenase, hydrogenase, phosphate acetyltransferase, acetate kinase, citrate synthase, succinate dehydrogenase, fumarate hydratase and catalase were below the limits of detection. The results suggest the occurrence of glycolysis, energy production by substrate level phosphorylation and a flavin, iron-sulfur protein mediated electron transport system as well as the absence of cytochrome mediated oxidative phosphorylation and functional Krebs cycle.
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PMID:Energy metabolism of the anaerobic protozoon Giardia lamblia. 610 7


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