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)

Electron paramagnetic resonance studies have indicated that nitrosodisulfonate binds to pig heart citrate synthase. Titration of the enzyme with nitrosodisulfonate revealed several binding sites for the probe per subunit with one site (KD approximately 0.1 mM) having a greater affinity than the others. The substrate, oxaloacetate, competed very effectively for one of the nitrosodisulfonate binding sites (KD less than 10(-2) mM) at the same time eliminating the weaker probe binding sites. Citrate and (R)- and (S)-malates also displaced the probe. Failure to resolve low- and high-field shoulder in the high gain--high modulation electron paramagnetic resonance spectra of the enzyme--nitrosodisulfonate system indicated that the bound probe was "weakly immobilized". However, the electron paramagnetic resonance spectrum of the bound probe changed to one typical of a "strongly immobilized" nitroxide upon the addition of a saturating concentration of the substrate acetyl coenzyme A (acetyl-CoA) to the enzyme--nitrosodisulfonate system, indicating the formation of a ternary acetyl-CoA-enzyme-probe complex. Titration of the acetyl-CoA saturated enzyme with the probe indicated one binding site per subunit (KD = 0.37 mM). Thus, nitrosodisulfonate may be considered as a paramagnetic analogue of oxaloacetate in its interaction with citrate synthase. These results are compared with our previous studies with this enzyme, employing a spin-labeled acyl coenzyme A (acyl-CoA) derivative [Weidman, S. W., Drysdale, G. R., & Mildvan, A. S. (1973) Biochemistry 12, 1874--1883].
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PMID:Interaction of a paramagnetic analogue of oxaloacetate with citrate synthase. 22 20

Naturally occurring citrate synthases fall into distinct molecular and catalytic types. Gram-negative bacteria produce a 'large' enzyme, allosterically inhibited by NADH and, in the facultative anaerobes such as Escherichia coli, also by 2-oxoglutarate. On the other hand, Gram-positive bacteria and all eukaryotes produce a 'small' citrate synthase which is insensitive to these metabolites. As a complement to structure-function studies we have explored the possibility of genetically altering one type of citrate synthase to the other. By mutagenesis and suitable selection we have succeeded in isolating a mutant of E. coli whose citrate synthase is both 'small' and insensitive to NADH and 2-oxoglutarate. Some characteristics of the enzyme are described. Such mutant enzymes offer a novel approach to the study of citrate synthase, its regulation and its natural diversity.
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PMID:Studies on a mutant form of Escherichia coli citrate synthase desensitised to allosteric effectors. 23 33

The changes induced by phenobarbital in cerebral enzymatic activities of the Krebs' cycle (citrate synthase, malate dehydrogenase) and electron transfer chain (total NADH-cytochrome c reductase and cytochrome oxidase) were studied. In addition, the activity of lactate dehydrogenase of acetylcholine esterase and of glutamate dehydrogenase was also studied. These enzymatic activities were evaluated in the homogenate in toto and in a crude mitochondrial fraction from rat brain. The modifications in some of these activities indicate that several new metabolic situations occur in brain tissue after phenobarbital treatment.
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PMID:Effect of phenobarbital on cerebral energy state and metabolism. Enzymatic activities. 23 Jun 18

Kinetics of utilization of acetyl coenzyme A by citrate synthase of a sea anemone, an osmoconformer, were compared with those of citrate synthases of various osmoregulators. The Kms of the latter enzymes were substantially increased by higher concentrations of salt and the enzyme exhibited hyperbolic substrate saturation curves. Citrate synthase from sea anemone, on the other hand, exhibited allosteric kinetics and minimal effects of salt on its Km. We suggest that the adaptive advantage of this enzymic property to a sedentary osmoconforming organism such as sea anemone is obvious since the osmoregulating creatures are apparently unable to maintain an appropriate low ionic environment in situ and thus probably the Km of their citrate synthases at a low level.
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PMID:Influence of possible in situ ionic environment on kinetics of purified citrate synthase from an osmoconformer sea anemone, Bunedosoma cavernata. 23 4

Certain key enzymes of alternative pathways of glucose metabolism, of amino acid metabolism and of redox systems have been measured in hydra and this profile compared with mammalian differentiated tissues with a view to locating pathways of specific importance in hydra. There was a marked constant proportionality in the major part of the enzymes investigated, the profile suggested a metabolic pattern geared to utilization of amino acids as a carbon source for biosynthesis and energy production and to the production and conservation of pyruvate. The importance of conversion to ionized forms was noted. The most notable specific proportion changes were the exceptionally low lactate dehydrogenase, malic enzyme and the relatively high citrate synthase. The proximal-distal gradients in hydra were examined and these gradients suggested a switch to a more anaerobic type of metabolism and an elevation of the pentose phosphate pathway as the basal region was approached. Measurements of the formation of 14CO2 from specifically labelled glucose provided additional evidence for the functional activity and polarity of the pentose phosphate pathway in hydra. The effect of oligomycin, which can reverse polarity in hydra, had a significant effect on gradients of enzymes eliminating all except that observed for G6P dehydrogenase. The profile suggested a movement towards a more anaerobic type of metabolism, in keeping with the known biochemical action of this inhibitor. It is suggested that redox states and/or phosphorylation states may be featured in the positional information of cells in hydra.
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PMID:Positional information and pattern regulation in hydra: enzyme profiles. 24 Sep 2

The metabolic and morphologic adaptation to physical training in skeletal muscle tissue of eleven middle-aged, physically untrained men was studied. Muscle biopsies were taken from the vastus lateralis before, after 8 weeks and after 6 months of physical training for analysis of metabolic and morphologic variables. Glucose tolerance test indicated increased insulin sensitivity after 6 months of physical training. The activities of glycogen phosphorylase, hexokinase and glucose-6-P-dehydrogenase were increased but other enzymes involved in glycogen turnover and glycolysis were unchanged after 6 months of physical traning. The activities of citrate synthase and cytochrome-c-oxidase, representing the oxidative capacity were significantly increased already after 8 weeks of physical training. The incorporation rate of palmitate-carbon into CO2 and triglycerides increased, and the incorporation rate of leucine-carbon into CO2 decreased with 6 months of physical training. The fiber diameter of both Type 1- and Type 2-fibers increased, while the mitochondrial volume increased predominantly in Type 2-fibers. Significant correlations were found between metabolic, physiologic and morphologic variables before and after physical training. The results indicate an increased oxidative capacity, mainly located to Type 2-fibers, and an increased utilization of fatty acids in response to this type of physical training.
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PMID:Physical training in man. Skeletal muscle metabolism in relation to muscle morphology and running ability. 32 4

The four isomers of hydroxycitrate have been tested as substrates and inhibitors for citrate synthase, citrate lyase, and ATP citrate lyase. None of the isomers served as a substrate for citrate synthase and they were moderate to weak inhibitors of this reaction. Of the four isomers, only (pncit)-(2S)-2-hydroxycitrate did not serve as a substrate for citrate lyase while (pncit)-(4S)-4-hydroxycitrate was the only isomer which did not serve as a substrate for ATP citrate lyase. No consistent pattern of reactivity or inhibitor potency was seen with the different isomeric hydroxycitrates. It is proposed that more than one mode of binding is possible between the isomers and the three different active sites.
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PMID:Reactivity and inhibitor potential of hydroxycitrate isomers with citrate synthase, citrate lyase, and ATP citrate lyase. 33 61

Levels of several intermediary metabolites were measured in cells grown in acetate medium in order to test the hypothesis that the glyoxylate cycle is repressed by phosphoenolpyruvate (PEP). Wild-type cells had less PEP than either isocitrate dehydrogenase - deficient cells (which had greater isocitrate lyase activity than the wild type) or isocitrate dehydrogenase - deficient, citrate synthase-deficient cells (which are poorly inducible). Thus induction of the glyoxylate cycle is more complicated than a simple function of PEP concentration. No correlation between enzyme activity and the level of oxaloacetate, pyruvate, or citrate was found either. Citrate was synthesized in citrate synthase-deficient mutants, possibly via citrate lyase.
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PMID:Acetate metabolism in Escherichia coli. 34 78

The possible induction of renal citrate synthase (E.C. 4.1.3.7) by aldosterone was evaluated in the adrenalectomized rat. Three hours after administration of aldosterone (0.8 microgram/100 g body wt), renal cortical and medullary citrate synthase activity was significantly increased as reported previously by Kinne and Kirsten (Kinne, R., Kirsten, R. 1968. Pfleugers Arch. 300:244). In contrast, no change in this activity was detected in the renal papilla or the liver, under the same conditions. Kinetic analysis revealed that injection of aldosterone had no effect on the KmS for acetyl-CoA and oxalacetate but augmented Vmax of renal medullary citrate synthase activity by 40%. The aldosterone-dependent increase in medullary citrate synthase activity was proportionate to the associated increase in the quantity of antiserum (specific for citrate synthase) required for half-maximal immuno-precipitation. The possibility that aldosterone induced the synthesis of citrate synthase was evaluated in two sets of experiments. In the first set, adrenalectomized rats were injected intraperitoneally with either aldosterone (0.8 microgram/100 g body wt) or the diluent, and simultaneously with 3H or 35S methionine (500 muCi/rat). The isotopes were reversed in about half of the experiments. Three hours after the injection, renal citrate synthase was isolated by ATP-sepharose column chromatography and immuno-precipitation with the specific antiserum. Aldosterone augmented methionine incorporation into renal citrate synthase by 55% but had no effect on incorporation into the hepatic enzyme. In the second set, adrenalectomized rats were injected with either aldosterone (0.8 microcram/100 g body wt) or the diluent, the kidneys were removed 1 hr later and medullary slices were incubated in either 3H- or 35S-methionine at 20 degrees for 2 hr. Mitochondrial citrate synthase was isolated either by ATP-sepharose column chromatography and immuno-precipitation, or by polyacrylamide gel electrophoresis. Aldosterone increased methionine incorporation into the immuno-precipitates by 30% and into the enzyme peak resolved by polyacrylamide gel electrophoresis by 43%. The latter increase was eliminated by prior administration of either actinomycin D (70--80 microgram/100 g body wt) or spirolactone (SC-26304) (80 microgram/100 g body wt). An equimolar dose of dexamethasone (0.8 microgram/100 g body wt) had no effect on the isotope ratio associated with citrate synthase activity in the polyacrylamide gels.
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PMID:Induction of citrate synthase by aldosterone in the rat kidney. 35 85

A 10 month old female infant was evaluated for severe lactic acidosis. Clinically she was well nourished and had a substantial amount of adipose tissue despite recurrent episodes of acidosis. Her psychomotor development was retarded, her movements were dystonic and generalized seizures punctuated her course. Metabolic abnormalities included elevated blood concentrations of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, alanine, proline and glycine, decreased blood concentrations of glutamine, aspartate, valine and citrate, and intermittent elevations of serum cholesterol. A trial on a high-fat diet worsened the clinical condition and intensified the ketoacidosis and hyperalaninemia. Analysis of hepatic tissue obtained by open biopsy revealed increased concentrations of lactate, alanine, acetyl-CoA and other short-chain acyl-CoA esters, and decreased concentrations of oxaloacetate, citrate, alpha-ketoglutarate, malate and aspartate. The blood and tissue metabolic perturbations reflected a deficiency of hepatic pyruvate carboxylase. The apparent Km of hepatic citrate synthase for oxaloacetate was 4.6 micrometer. Calculated tissue oxaloacetate concentrations were 0.50--0.84 micrometer suggesting that tricarboxylic acid cycle activity was severely limited by the decreased availability of this substrate. An iv glucose tolerance test resulted in the paradoxical synthesis of ketone bodies. This observation, coupled with the intermittent hypercholesterolemia and the increased tissue acetyl-CoA concentrations, suggests that pyruvate carboxylase is important in modulating the fractional distribution of intracellular acetyl-CoA between the tricarboxylic acid cycle, the beta-hydroxy-beta-methyl-glutaryl-CoA cycle (and the synthesis of cholesterol and ketone bodies), and fatty acid synthesis. Treatment in future cases might be directed toward increasing tissue concentrations of oxaloacetate.
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PMID:The clinical and biochemical implications of pyruvate carboxylase deficiency. 41 60


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