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 contents of some intermediates of glycolysis, the citric acid cycle and adenine nucleotides have been measured in the freeze-clamped locust flight muscle at rest and after 10s and 3min flight. The contents of glucose 6-phosphate, pyruvate, alanine and especially fructose bisphosphate and triose phosphates increased markedly upon flight. The content of acetyl-CoA is decreased after 3min flight whereas that of acetylcarnitine is decreased markedly after 10s flight, but returns towards the resting value after 3min flight. The content of citrate is markedly decreased after both 10s and 3min flight, whereas that of isocitrate is changed very little after 10s and is increased by 50% after 3min. The content of oxaloacetate is very low in insect flight muscle and hence it was measured by a sensitive radiochemical assay. The content of oxaloacetate increased about 2-fold after 3min flight. A similar change was observed in the content of malate. The content of ATP decreased about 15%, whereas those of ADP and AMP increased about 2-fold after 3min flight. 2. Calculations based on O(2) uptake of the intact insect indicate that the rate of the citric acid cycle must be increased >100-fold during flight. Consequently, if citrate synthase catalyses a non-equilibrium reaction, the activity of the enzyme must increase >100-fold during flight. However, changes in the concentrations of possible regulators of citrate synthase, oxaloacetate, acetyl-CoA and citrate (which is an allosteric inhibitor), are not sufficient to account for this change in activity. It is concluded that there may be much larger changes in the free concentration of oxaloacetate than are indicated by the changes in the total content of this metabolite or that other unknown factors must play an additional role in the regulation of citrate synthase activity. 3. The increased content of oxaloacetate could be produced via pyruvate carboxylase, which may be stimulated during the early stages of flight by the increased concentration of pyruvate. 4. The decreases in the concentrations of citrate and alpha-oxoglutarate indicate that isocitrate dehydrogenase and oxoglutarate dehydrogenase may be stimulated by factors other than their pathway substrates during the early stages of flight. 5. Calculated mitochondrial and cytosolic NAD(+)/NADH ratios are both increased upon flight. The change in the mitochondrial ratio indicates the importance of the intramitochondrial ATP/ADP concentration ratio in the regulation of the rate of electron transfer in this muscle.
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PMID:Changes in the contents of adenine nucleotides and intermediates of glycolysis and the citric acid cycle in flight muscle of the locust upon flight and their relationship to the control of the cycle. 43 78

The crystal structure of pig heart citrate synthase was analyzed at 0.35-nm resolution. Chain tracing was possible and an initial molecular model constructed. The dimensions of the dimer molecule (located on a crystallographic diad) are 7.5 x 6.0 x 9.0 nm. The chain folding is characterized by the predominance of helices and the absence of sheet structure. The electron density accounts for 355 residues per monomer, so that about 80 residues must be disordered in the crystal. The disordered segment in probably N-terminal. The ordered part consists of two closely associated domains, a large domain with 300 residues and a C-terminal domain of 55 residues consisting of 3(anti)parallel helices. The large domain is built from 12 helical segments, some of which are buried in the interior of the molecule. Inhibitor binding studies with citrate and CoA revealed citrate binding sites but showed no electron density for CoA. It is suggested that CoA binds to the disordered, flexible N-terminal domain. Experiments of limited proteolysis with trypsin showed that under conditions a segment of Mr 9000 is cleaved off selectively. The remaining 35 000-Mr part is dimeric.
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PMID:Crystal structure analysis of the tetragonal crystal form are preliminary molecular model of pig-heart citrate synthase. 43 30

The mitochondrial matrix subfractions from rat liver, kidney cortex, brain, heart, and skeletal muscle were isolated and their protein components were resolved by two-dimensional polyacrylamide gel electrophoresis, revealing between 120 and 150 components for each matrix subfraction. Excellent resolution was obtained utilizing a pH 5 to 8 gradient in the first dimension and in 8 to 13% exponential acrylamide gradient in the second dimension, increasing the number of mitochondrial matrix proteins observed 3-fold over one-dimensional systems. Protein components tentatively identified by co-migration with pure enzymes and by known tissue distributions are carbamoyl-phosphate synthetase (EC 2.7.2.5), ornithine transcarbamylase (EC 2.1.3.3), glutamate dehydrogenase (EC 1.4.1.3), pyruvate carboxylase (EC 6.4.1.1), citrate synthase (EC 4.1.3.7), fumarase (EC 4.2.1.2), aconitase (EC 4.2.1.3), alpha-ketoglutarate dehydrogenase (EC 1.2.4.2), dihydrolipoyl transsuccinylase (EC 2.3.1.12), lipoamide dehydrogenase (EC 1.6.4.3), glutamate-aspartate aminotransferase (EC 2.6.1.1), and the two subunits of pyruvate dehydrogenase (EC 1.2.4.1). Protein components unambiguously identified by peptide mapping are citrate synthase, aconitase, and pyruvate carboxylase. The inner membrane subfraction from rat liver mitochondria was also resolved two dimensionally; the alpha and beta subunits of ATPase (F1) (EC 3.6.1.3) were identified by peptide mapping.
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PMID:Resolution of rat mitochondrial matrix proteins by two-dimensional polyacrylamide gel electrophoresis. 44 63

Early removal of the optic cup of the chick embryo prevents innervation of the contralateral optic lobe. This reduces the rate of development od citrate synthetase. The posthatch increase of the level of this enzyme related to oxidative metabolism is not impaired by denervation of the chick optic lobe.
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PMID:Development of oxidative metabolism in the non-innervated optic lobe of the chick. 46 73

The activity of lipoamide dehydrogenase and two closely related enzymes was studied simultaneously in early, mild, and late passage fibroblast cultures. Friedreich's ataxia fibroblasts tended to lose pyruvate dehydrogenase and citrate synthase activities, while lipoamide dehydrogenase activity remained constant with aging of the cells. Mean pyruvate dehydrogenase activity was lower over-all in fibroblasts from ataxics. Mean citrate synthase activity was higher in ataxic fibroblasts. Present tissue culture media do not represent the best conditions in which to reproduce cofactor binding defects such as those found in other genetic diseases with structural enzyme mutations.
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PMID:Pyruvate dehydrogenase, lipoamide dehydrogenase and citrate synthase activity in fibroblasts from patients with Friedreich's and Charlevoix-Saguenay ataxia. 48 17

A sensitive micromethod for the determination of Coenzyme A and its esters down to about 0.2 pmol in a volume of 10 microliters and of the activity of citrate synthase is outlined. Epidermal material from healthy and psoriatic skin was utilized in microgram quantity as tissue source. The assay utilizes the ketoglutarate dehydrogenase reaction to yield NADH on addition of free Coenzyme A and the subsequent measurement of NADH by a bioluminescent reaction with Acromobacter fischerii. The total Coenzyme A content in six healthy subjects measured in stratum Malpighii was 1.58 +/- 0.19 mmol per kg dry weight. In six psoriatic patients non-involved and involved epidermis contained 1.51 +/- 0.27 and 1.50 +/- 0.25 mmol/kg, respectively. Long-chain acyl-Coenzyme A comprised about 20% in lesion-free skin and 60% of total content in the involved psoriatic epidermis. The activity of citrate synthase in basal layers of healthy epidermis was 0.30 +/- 0.04 mkat/kg dry weight.
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PMID:The measurement of coenzyme A and a coenzyme A-dependent enzyme. In microdissected epidermal material using coupled enzyme and bioluminescent reactions. 50 26

A test model of studying the effects of chronic pharmacological treatment on cerebral metabolism related to energy transduction was developed. The most useful biochemical parameters were the cerebral enzymatic activities related to the glycolytic pathway (lactate dehydrogenase), the Krebs' cycle (citrate synthetase and malate dehydrogenase) and the electron transfer chain (total NADH-cytochrome c reductase and cytochrome oxidase). The model is based on the natural growth-dependent changes occurring in the rat during aging (from 10 to 60 weeks of life). As test drug, 10-methoxy-1,6-dimethyl-ergoline-8 beta-methanol-(5-bromonicotinate) (nicergoline, Sermion) was administered daily for three periods of 16 weeks each (10-26, or 28-44, or 44-60 weeks of life) by two different administration routes (oral and i.p.), and at two different dose levels: oral 1 or 4, i.p. 0.25 or 1 mg/kg. Biochemical data were obtained blindly after 4, 8, 12 and 16 weeks of treatment. The drug tested exerted different effects which were dependent on the various administration periods and the administration routes. No dose-effect relationship was established.
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PMID:[Cerebral enzymatic activities related to energy transduction processes. A model for the evaluation of pharmacological changes in the brain of the adult rat]. 54 66

Deviations from Michealis-Menten kinetics in the pig-heart citrate synthase (citrate-oxaloacetate-lyase(pro-3S-CH2-COO-leads to acetyl-CoA), EC 4.1.3.7) system have been characterized and analyzed in view of the kinetic theory described in the preceding paper. The enzymic condensation reaction between acetyl-CoA and oxaloacetate is subject to substrate-inhibition by acetyl-CoA. This can be attributed to the formation of a productive enzyme-acetyl-CoA complex with a dissociation constant of 110 uM. The binding of acetyl-CoA to the enzyme decreases the on-velocity constant for oxaloacetate-binding from 4000 min-1- micrometer-1 to 1700 min-1-micrometer-1. The affinity of citrate synthase for oxaloacetate increase at least 20-fold on the binding of acetyl-CoA. The latter cooperativity effect can be attributed to a more than 45-fold decrease of the off-velocity constant for oxaloacetate-binding.
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PMID:Substrate-inhibiton by acetyl-CoA in the condensation reaction between oxaloacetate and acetyl-CoA catalyzed by citrate synthase from pig heart. 56 Aug 67

1. The changes with the time of the activities of some energy-supplying enzymes and of the hydrolytic enzyme, acid phosphatase, were studied over 2 weeks of complete ischaemia, produced in the rat soleus muscle by section of the abdominal aorta and terminal devascularization, leaving nerve and tendon intact. 2. Activities of glycolytic enzymes, oxidative enzymes, hexokinase and acid phosphatase are affected in a different manner. Activities of the glycolytic enzymes, lactate dehydrogenase, triosephosphate dehydrogenase and glycerolphosphate dehydrogenase, are lowest on the 1st day and increase thereafter. The first two reach the control values again on the 4th and 14th day, respectively, while glycerolphosphate dehydrogenase reaches about 50% of the control value on the 14th day. The maximum decrease in activity of the oxidative enzymes, citrate synthase, beta-hydroxyacyl-CoA-dehydrogenase and malate dehydrogenase occurs later (4th day); thereafter their activity returns slowly to control values, but does not reach them even on the 14th day. Hexokinase activity is slightly decreased on the 1st day; then it increased and reached on the 7th day twice the control value. Thus on the 1st day the activity of the enzymes of aerobic metabolism prevail, and on the 4th day those of anaerobic carbohydrate (glucose) metabolism; the recovery of enzyme activity of aerobic oxidation occurs later. 3. Acid phosphatase activity increased from the 2nd day onwards, reaching up to 3 times the control value on the 4th day and still twice that value on the 14th day. This agrees well with the histochemical picture of acid phosphatase. 4. Histochemical changes of alkaline phosphatase activity reveal destruction of capillary endothelial cells during the first few days after operation and their later proliferation from the periphery, correlating with the loss and recovery of oxidative enzyme activity.
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PMID:Effects of ischaemia on enzyme-activities in the soleus muscle of the rat. 57 Nov 16

The synthesis of a new coenzyme A analogue, N6-[N-(6-aminohexyl)carbamoylmethyl]-CoA, suitable for immobilisation through its terminal amino group to support matrices, is described. The synthetic route starts with bis(CoA) and involves the following steps: alkylation with iodoacetic acid and rearrangement yielding bis(N6-carboxymethyl-CoA), elongation of the carboxymethyl terminal with 1,6-diaminohexane using carbodiimide to yield bis(N6-[N-(6-aminohexyl)-carbamoylmethyl]-CoA) and finally the splitting of this bis[CoA analogue) through reduction with dithiothreitol to give the final product in approximately 10% overall yield. This CoA analogue showed 'coenzymic activity' with the enzymes acetyl-CoA synthetase, phosphotransacetylase and succinic thiokinase. Covalent binding of the CoA analogue to Sepharose 4B was normally carried out using its S-(5-thio-2-nitrobenzoic acid) derivative as this allows a convenient way for determining the amount of ligand coupled, based on the amount of 5-thio-2-nitrobenzoic acid liberated from the gel after reduction with dithiothreitol. After covalent binding of the CoA analogue to water-soluble activated dextran 70, the analogue was recycled while present in an ultrafiltration cell using the enzymes phosphotransacetylase and citrate synthase. The reaction was followed by measuring the citrate formed on addition of acetylphosphate and oxaloacetate. In affinity chromatographic studies it was shown that the CoA-Sepharose preparation could bind the CoA-dependent enzymes citrate synthase and succinic thiokinase and these could be biospecifically eluted using soluble CoA.
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PMID:N6-[N-(6-Aminohexyl)carbamoylmethyl]-coenzyme A. Synthesis and application in affinity chromatography and as an immobilized active coenzyme. 57 88


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