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. A method is described for extracting separately mitochondrial and extramitochondrial enzymes from fat-cells prepared by collagenase digestion from rat epididymal fat-pads. The following distribution of enzymes has been observed (with the total activities of the enzymes as units/mg of fat-cell DNA at 25 degrees C given in parenthesis). Exclusively mitochondrial enzymes: glutamate dehydrogenase (1.8), NAD-isocitrate dehydrogenase (0.5), citrate synthase (5.2), pyruvate carboxylase (3.0); exclusively extramitochondrial enzymes: glucose 6-phosphate dehydrogenase (5.8), 6-phosphogluconate dehydrogenase (5.2), NADP-malate dehydrogenase (11.0), ATP-citrate lyase (5.1); enzymes present in both mitochondrial and extramitochondrial compartments: NADP-isocitrate dehydrogenase (3.7), NAD-malate dehydrogenase (330), aconitate hydratase (1.1), carnitine acetyltransferase (0.4), acetyl-CoA synthetase (1.0), aspartate aminotransferase (1.7), alanine aminotransferase (6.1). The mean DNA content of eight preparations of fat-cells was 109mug/g dry weight of cells. 2. Mitochondria showing respiratory control ratios of 3-6 with pyruvate, about 3 with succinate and P/O ratios of approaching 3 and 2 respectively have been isolated from fat-cells. From studies of rates of oxygen uptake and of swelling in iso-osmotic solutions of ammonium salts, it is concluded that fat-cell mitochondria are permeable to the monocarboxylic acids, pyruvate and acetate; that in the presence of phosphate they are permeable to malate and succinate and to a lesser extent oxaloacetate but not fumarate; and that in the presence of both malate and phosphate they are permeable to citrate, isocitrate and 2-oxoglutarate. In addition, isolated fat-cell mitochondria have been found to oxidize acetyl l-carnitine and, slowly, l-glycerol 3-phosphate. 3. It is concluded that the major means of transport of acetyl units into the cytoplasm for fatty acid synthesis is as citrate. Extensive transport as glutamate, 2-oxoglutarate and isocitrate, as acetate and as acetyl l-carnitine appears to be ruled out by the low activities of mitochondrial aconitate hydratase, mitochondrial acetyl-CoA hydrolyase and carnitine acetyltransferase respectively. Pathways whereby oxaloacetate generated in the cytoplasm during fatty acid synthesis by ATP-citrate lyase may be returned to mitochondria for further citrate synthesis are discussed. 4. It is also concluded that fat-cells contain pathways that will allow the excess of reducing power formed in the cytoplasm when adipose tissue is incubated in glucose and insulin to be transferred to mitochondria as l-glycerol 3-phosphate or malate. When adipose tissue is incubated in pyruvate alone, reducing power for fatty acid, l-glycerol 3-phosphate and lactate formation may be transferred to the cytoplasm as citrate and malate.
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PMID:The intracellular localization of enzymes in white-adipose-tissue fat-cells and permeability properties of fat-cell mitochondria. Transfer of acetyl units and reducing power between mitochondria and cytoplasm. 439 82

The activities of five enzymes involved in acetyl-CoA synthesis, pyruvate dehydrogenase complex, ATP citrate lyase, carnitine acetyltransferase, acetyl-CoA synthetase, and citrate synthase, were determined in normal nucleus interpeduncularis and nucleus interpeduncularis in which cholinergic terminals were removed following lesion of the habenulointerpeduncular tract. The activities of aspartate transaminase, fumarase, and GABA transaminase also were determined to compare the effect of lesion on other mitochondrial enzymes which are not linked to the biosynthesis of ACh. In normal nucleus interpeduncularis the activities of carnitine acetyltransferase and pyruvate dehydrogenase complex were higher than the activity of ChAT (choline acetyltransferase), whereas the activities of acetyl-CoA synthetase and citrate synthase were considerably lower than that of ChAT. The effect of the lesion separated the enzymes into two groups: the activities of pyruvate dehydrogenase complex, carnitine acetyltransferase, fumarase and aspartate transaminase decreased by 30--40%, whereas the activities of the other enzymes descreased 5--15%. ChAT activity was in all cases less than 15% of normal. It could be concluded that none of the acetyl-CoA synthesizing enzymes decreased to the degree that ChAT did. Only pyruvate dehydrogenase complex and carnitine acetyltransferase seem to be localized in cholinergic terminals to a significant degree. ATP citrate lyase as well as acetyl-CoA synthetase seem to have less significance in supporting acetyl-CoA formation in cholinergic nerve terminals.
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PMID:Acetyl-CoA synthesizing enzymes in cholinergic nerve terminals. 610 88

The activities of ATP-citrate lyase in frog, guinea pig, mouse, rat, and human brain vary from 18 to 30 mu mol/h/g of tissue, being several times higher than choline acetyltransferase activity. Activities of pyruvate dehydrogenase and acetyl coenzyme A synthetase in rat brain are 206 and 18.4 mu mol/h/g of tissue, respectively. Over 70% of the activities of both choline acetyltransferase and ATP-citrate lyase in secondary fractions are found in synaptosomes. Their preferential localization in synaptosomes and synaptoplasm is supported by RSA values above 2. Acetyl CoA synthetase activity is located mainly in whole brain mitochondria (RSA, 2.33) and its activity in synaptoplasm is low (RSA, 0.25). The activities of pyruvate dehydrogenase, citrate synthase, and carnitine acetyltransferase are present mainly in fractions C and Bp. No pyruvate dehydrogenase activity is found in synaptoplasm. Striatum, cerebral cortex, and cerebellum contain similar activities of pyruvate dehydrogenase, citrate synthase, carnitine acetyltransferase, fatty acid synthetase, and acetyl-CoA hydrolase. Activities of acetyl CoA synthetase, choline acetyltransferase and ATP-citrate lyase in cerebellum are about 10 and 4 times lower, respectively, than in other parts of the brain. These data indicate preferential localization of ATP-citrate lyase in cholinergic nerve endings, and indicate that this enzyme is not a rate limiting step in the synthesis of the acetyl moiety of ACh in brain.
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PMID:Regional and subcellular distribution of ATP-citrate lyase and other enzymes of acetyl-CoA metabolism in rat brain. 610 1

The activities of choline acetyltransferase and ATP-citrate lyase were significantly correlated (r = 0.995) in fractions of small and large synaptosomes isolated from rat hippocampus and cerebellum. The activities of these two enzymes did not correlate with those of pyruvate dehydrogenase, carnitine acetyltransferase, citrate synthase, acetyl-CoA synthetase, lactate dehydrogenase, or with the rate of high-affinity glutamate uptake in the synaptosomal fractions. The results provide additional evidence linking ATP-citrate lyase to the cholinergic system in the brain.
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PMID:ATP-citrate lyase and other enzymes of acetyl-CoA metabolism in fractions of small and large synaptosomes from rat brain hippocampus and cerebellum. 613 19

S-Dimethylarsino-CoA was synthesized by acylation of CoA with dimethylchloroarsine. The new analogue of acetyl-CoA was tested as an active-site-directed irreversible inhibitor of phosphotransacetylase (EC 2.3.1.8), carnitine acetyltransferase (EC 2.3.1.7) and citrate synthase (EC 4.1.3.7). Irreversible inhibition was observed only with phosphotransacetylase, which was derivatized via a simple bimolecular process (k2 = 197 +/- 15 min-1 . M-1). Acetyl-CoA provided complete substrate protection against the inactivation, while phosphate (a substrate) and desulfo-CoA (a competitive inhibitor) provided a partial protection. The inactivation was not reversed by dithiothreitol. The new reagent was a linear competitive inhibitor versus acetyl-CoA with both carnitine acetyltransferase (Ki = 41 microM) and citrate synthase (Ki = 20 microM). Chemical studies showed that S-dimethylarsino-CoA reacts with the thiol of N alpha-acetylcysteine but not with the side-chain functional groups of histidine and lysine. The nature of the chemical modification of cysteine was determined by investigating a model system. Thus the chemical reaction between the thioarsenite linkage of S-dimethylarsinobenzylmercaptan and the thiol of cysteine was shown to involve transesterification of the dimethylarsino group.
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PMID:Irreversible inhibition of phosphotransacetylase by S-dimethylarsino-CoA. 663 58

We have synthesized S-acetonyl-CoA from CoASH and 1-bromoacetone. This thioether-containing structural analogue of acetyl-CoA is a potent competitive inhibitor, with respect to acetyl-CoA, of citrate synthase, phosphotransacetylase, and carnitine acetyltransferase. This analog will not activate Escherichia coli phosphoenolpyruvate carboxylase or rat liver pyruvate carboxylase, two enzymes which require acetyl-CoA as an obligate activator. Furthermore, acetonyl-CoA will not compete with acetyl-CoA for binding to these enzymes showing the apparent absolute requirement of these two enzymes for a thioester group on the activating ligand. S-Acetonyl-CoA should be a useful reagent in the investigation of acetyl-CoA-requiring processes.
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PMID:S-acetonyl-CoA. A nonreactive analog of acetyl-CoA. 699 55

Electrolytic lesions made in the medial septum of the rat brain caused an 80% decrease in the activity of choline acetyltransferase and a 33% reduction in ATP-citrate lyase activity in the synaptosomal fraction from the hippocampus. Decreases in the activities of the two enzymes in the cytosol (S3) fraction were 70 and 13%, respectively. The activities of pyruvate dehydrogenase, citrate synthase, acetyl-CoA synthase, and carnitine acetyltransferase in crude hippocampal homogenates and in subcellular fractions were not affected by septal lesions. The data indicate that ATP-citrate lyase is linked to the septal-hippocampal pathway and that the enzyme is preferentially located in cholinergic nerve endings that terminate within the hippocampus.
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PMID:Effects of septal lesions on enzymes of acetyl-CoA metabolism in the cholinergic system of the rat hippocampus. 708 27

Several aspects of fatty acids metabolism have been examined in skeletal muscle mitochondria from both strain 129 dystrophic (dy/dy) and myodystrophic (myd/myd) mice. Skeletal muscle mitochondria from dy/dy mice showed significantly decreased state 3 respiratory rates with both palmityl- and acetyl-carnitine + malate as substrates when compared with their normal littermate controls. A similar, though less severe impairment in acylcarnitine oxidation by mitochondria from myd/myd skeletal muscle has also been shown by us in a previous study. In the present study, kinetic measurements revealed decreased activities of the reverse carnitine palmityltransferase (palmitylcarnitine + CoASH as substrates) in intact mitochondria from dy/dy muscle, and of citrate synthase in myd/myd muscle mitochondria. However, neither of these reactions appeared to be rate limiting for acylcarnitine oxidation in mouse skeletal muscle mitochondria. All other enzyme activities of cofactor contents measured were either comparable to those of controls or were higher. The results reported here indicate that neither of the impairments in acylcarnitine oxidation by skeletal muscle mitochondria from dy/dy or myd/myd mice is due to deficiencies in either carnitine palmityltransferase, carnitine acetyltransferase, citrate synthase, coenzyme A, or substrate-reducible flavoprotein.
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PMID:Fatty acid metabolism in skeletal muscle mitochondria from two strains of dystrophic mice. 744 19

The case of a female patient with cardio-encephalo-myopathy who died of her illness at one year of age, similarly to her three sisters, is reported. In autopsy samples, like muscle, heart, liver and cerebellum activities of several mitochondrial enzymes were determined. In the skeletal muscle serious decrease of carnitine acetyltransferase was observed (from the normal 4.8 U/g to 0.08 U/g wet weight), while in other tissues this activity was normal. In the muscle activities of several other mitochondrial enzymes were also decreased (cytochrome oxidase, NADH cytochrome C oxidoreductase, citrate synthase), while in other tissues there were no similar changes. Serious distortion was observed in the structure of the majority of mitochondria of muscle and heart by electronmicroscopy. The number of the Purkinje-cells in the cerebellum decreased, and the cells were shrunken, their axons were fragmented and disoriented. Also the structure of the mitochondria was abnormal in the Purkinje-cells, while it was normal in other areas of the cerebrum. In te tissues of the patient normal and deleted mitochondrial DNA coexisted as which could explain the genetic background of this disease at molecular level.
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PMID:[Mitochondrial DNA deletion in hereditary cardio-encephalo-myopathy]. 759 86

We investigated how NADH generated during peroxisomal beta-oxidation is reoxidized to NAD+ and how the end product of beta-oxidation, acetyl-CoA, is transported from peroxisomes to mitochondria in Saccharomyces cerevisiae. Disruption of the peroxisomal malate dehydrogenase 3 gene (MDH3) resulted in impaired beta-oxidation capacity as measured in intact cells, whereas beta-oxidation was perfectly normal in cell lysates. In addition, mdh3-disrupted cells were unable to grow on oleate whereas growth on other non-fermentable carbon sources was normal, suggesting that MDH3 is involved in the reoxidation of NADH generated during fatty acid beta-oxidation rather than functioning as part of the glyoxylate cycle. To study the transport of acetyl units from peroxisomes, we disrupted the peroxisomal citrate synthase gene (CIT2). The lack of phenotype of the cit2 mutant indicated the presence of an alternative pathway for transport of acetyl units, formed by the carnitine acetyltransferase protein (YCAT). Disruption of both the CIT2 and YCAT gene blocked the beta-oxidation in intact cells, but not in lysates. Our data strongly suggest that the peroxisomal membrane is impermeable to NAD(H) and acetyl-CoA in vivo, and predict the existence of metabolite carriers in the peroxisomal membrane to shuttle metabolites from peroxisomes to cytoplasm and vice versa.
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PMID:The membrane of peroxisomes in Saccharomyces cerevisiae is impermeable to NAD(H) and acetyl-CoA under in vivo conditions. 762 49


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