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

---

Query: EC:2.3.3.1 (citrate synthase)
4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dibutyryl cyclic AMP and butyrate inhibited growth of S-20 (cholinergic) and NIE-115 (adrenergic) neuroblastoma clones. Both these drugs resulted in a parallel increase of choline acetyltransferase and ATP-citrate lyase activities in S-20 neuroblastoma cells. On the other hand, the increase in tyrosine hydroxylase activity in NIE-115 caused by these drugs was not accompanied by a significant change in ATP-citrate lyase activity. Both dibutyryl cyclic AMP and butyrate caused a decrease in fatty acid synthetase activity in both cell lines. The activities of pyruvate dehydrogenase, citrate synthase, choline acetyltransferase, and lactate dehydrogenase in both S-20 and NIE-115 cells were not significantly influenced by the drugs. ATP-citrate lyases from S-20 and NIE-115 had similar kinetic and immunological properties, and their subunits had the same molecular weight as the rat liver enzyme. These data indicate that the differential regulation of ATP-citrate lyase activity in cholinergic and adrenergic cells does not result from the existence of different molecular forms of the enzyme in these cell lines. They also provide further evidence to support the hypothesis that ATP-citrate lyase activity increases during maturation of normal cholinergic neurons and decreases in noncholinergic cells of the brain.
...
PMID:The enzymes of acetyl-CoA metabolism in differentiating cholinergic (s-20) and noncholinergic (NIE-115) neuroblastoma cells. 630 53

Intracellular and extracellular concentrations of citrate and the specific activities of ten different enzymes in Candida curvata D were examined in relation to lipid biosynthesis in batch and continuous culture. Citrate was found to accumulate prior to lipid production and declined markedly as lipid accumulated in batch culture. The cells excreted citrate as the culture became nitrogen-limiting after 30 hr of growth, but little more was expelled after 40 hr when lipid accumulation was more marked. In continuous culture, only low levels of citrate were detected at the lower dilution rates and citrate was completely absent from both the cells and medium above a dilution rate of 0.1/hr. The activity of malic enzyme, malate dehydrogenase and ATP:citrate lyase increased in batch culture on lipid accumulated and, in continuous culture, both malic enzyme and ATP:citrate lyase varied in parallel with the specific rate of lipid synthesis which increased with increasing dilution rate. Activity of malate dehydrogenase, citrate synthase and glucose-6-phosphate dehydrogenase decreased with increasing dilution rate. The regulatory significance of these enzymes in lipid accumulation by C. curvata is discussed.
...
PMID:Biochemical activities during lipid accumulation in Candida curvata. 663 68

The activities of pyruvate dehydrogenase, citrate synthase, and choline acetyltransferase in rat brain synaptosomes increased during ontogenesis by 3 and 14 times, respectively. Activity of ATP-citrate lyase decreased by 26% during the same period. Pyruvate consumption by synaptosomes from 1-day-old animals was 40% lower than that found in older rats; however, citrate efflux from intrasynaptosomal mitochondria in immature synaptosomes was over twice as high as that in mature ones. The rates on production of synaptoplasmic acetyl-CoA by ATP-citrate lyase were 1.03, 1.40, and 0.49 nmol/min/mg protein in 1-, 10-day-old, and adult rats, respectively. 3-Bromopyruvate (0.5 mM) inhibited pyruvate consumption by 70% and caused a complete block of citrate utilization by citrate lyase in every age group. Parameters of citrate metabolism in cerebellar synaptosomes were the same as those in cerebral ones. These data indicate that production of acetyl-CoA from citrate in synaptoplasm may be regulated either by adaptative, age-dependent changes in permeability and carrier capacity of the mitochondrial membrane or by the inhibition of synthesis of intramitochondrial acetyl-CoA. ATP-citrate lyase activity is not a rate-limiting factor in this process. Metabolic fluxes of pyruvate to cytoplasmic citrate and acetyl-CoA are presumably the same in both cholinergic and noncholinergic nerve endings. The significance of citrate release from intrasynaptosomal mitochondria as a regulatory step in acetylcholine synthesis is discussed.
...
PMID:The contribution of citrate to the synthesis of acetyl units in synaptosomes of developing rat brain. 706 46

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.
...
PMID:Effects of septal lesions on enzymes of acetyl-CoA metabolism in the cholinergic system of the rat hippocampus. 708 27

[14C]Acetyl-CoA was found to react spontaneously with dithiothreitol to give a relatively apolar product which was readily extractable into a butanol-toluene scintillant. This technique was used in rapid, reproducible assay for rat brain ATP:citrate lyase using [1,5-14C]citrate as substrate. The tissue extract, a 14,000 g supernatant, exhibited a lyase activity of approximately 7 nmol acetyl-CoA produced/min per mg supernatant protein, and was inhibited greater than or equal to 79% by alpha-ketoglutaric acid (10 mM), Cu2+ (1 mM) and Zn2+ (1 mM). [14C]Oxaloacetate, [14C]malate and endogenous citrate synthase were found not to interfere significantly with lyase estimations, but NADH was required in the reaction mixture to inhibit acetyl-CoA hydrolase activity.
...
PMID:The interaction of dithiothreitol and acetyl coenzyme A in a radiochemical assay for rat brain ATP:citrate oxaloacetate lyase. 725 96

We have developed and implemented a model that can predict the positional isotopomer distribution of various hepatic metabolites labeled with [U-13C3]lactate and/or [U-13C3]pyruvate for given relative flux rates through the citric acid cycle and gluconeogenesis reactions. Our model includes (i) isotopic exchange between alpha-ketoglutarate and glutamate, (ii) a reversible isocitrate dehydrogenase reaction, (iii) an active ATP-citrate lyase, and (iv) aspartate and malate shuttles with separate cytosolic and mitochondrial pools for oxaloacetate, malate, and fumarate. A parameter estimation routine fit the mass isotopomer distribution of selected metabolites measured by gas chromatography-mass spectrometry to the model predicted distributions. We fit measured mass isotopomer distributions of phosphoenolpyruvate, citrate, alpha-ketoglutarate, glutamate, and pyruvate isolated from fasted rat livers perfused with [U-13C3]lactate + [U-13C3]pyruvate. This fitting yielded rates which we express relative to that of pyruvate carboxylase: citric acid cycle represented by the irreversible alpha-ketoglutarate dehydrogenase = 0.32; citrate synthase = 0.64; reversal of isocitrate dehydrogenase = 0.52; citrate lyase = 0.33, aspartate shuttle = 0.24, and malate shuttle = 0.44. Rates calculated for the cytosolic and mitochondrial fumarate and malate dehydrogenase reactions are subject to uncertainties as indicated by identifiability analyses. Previous forms of our model that did not include pyruvate kinase, exchange of alpha-ketoglutarate with glutamate, reversibility of isocitrate dehydrogenase, and/or ATP-citrate lyase activity were not as successful at predicting our measured values. This model offers a general tool for studying the regulation of the citric acid cycle and gluconeogenesis and can be readily modified for any 13C-labeled lactate or pyruvate substrate.
...
PMID:Modeling of liver citric acid cycle and gluconeogenesis based on 13C mass isotopomer distribution analysis of intermediates. 773 Mar 5

Common molecular changes in cancer cells are high carbon flux through the glycolytic pathway and overexpression of fatty acid synthase, a key lipogenic enzyme. Since glycerol 3-phosphate dehydrogenase creates a link between carbohydrates and the lipid metabolism, we have investigated the activity of glycerol 3-phosphate dehydrogenase and various lipogenic enzymes in human bladder cancer. The data presented in this paper indicate that glycerol 3-phosphate dehydrogenase activity in human bladder cancer is significantly higher compared to adjacent non-neoplastic tissue, serving as normal control bladder tissue. Increased glycerol 3-phosphate dehydrogenase activity is accompanied by increased enzyme activity, either directly (fatty acid synthase) or indirectly (through ATP-citrate lyase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and citrate synthase) involved in fatty acid synthesis. Coordinated upregulation of glycerol 3-phosphate dehydrogenase and lipogenic enzymes activities in human bladder cancer suggests that glycerol 3-phosphate dehydrogenase supplies glycerol 3-phosphate for lipid biosynthesis.
...
PMID:Increased activity of glycerol 3-phosphate dehydrogenase and other lipogenic enzymes in human bladder cancer. 1460 88

The hyperthermophilic archaeon Pyrobaculum islandicum uses the citric acid cycle in the oxidative and reductive directions for heterotrophic and autotrophic growth, respectively, but the control of carbon flow is poorly understood. P. islandicum was grown at 95 degrees C autotrophically, heterotrophically, and mixotrophically with acetate, H2, and small amounts of yeast extract and with thiosulfate as the terminal electron acceptor. The autotrophic growth rates and maximum concentrations of cells were significantly lower than those in other media. The growth rates on H2 and 0.001% yeast extract with and without 0.05% acetate were the same, but the maximum concentration of cells was fourfold higher with acetate. There was no growth with acetate if 0.001% yeast extract was not present, and addition of H2 to acetate-containing medium greatly increased the growth rates and maximum concentrations of cells. P. islandicum cultures assimilated 14C-labeled acetate in the presence of H2 and yeast extract with an efficiency of 55%. The activities of 11 of 19 enzymes involved in the central metabolism of P. islandicum were regulated under the three different growth conditions. Pyruvate synthase and acetate:coenzyme A (CoA) ligase (ADP-forming) activities were detected only in heterotrophically grown cultures. Citrate synthase activity decreased in autotrophic and acetate-containing cultures compared to the activity in heterotrophic cultures. Acetylated citrate lyase, acetate:CoA ligase (AMP forming), and phosphoenolpyruvate carboxylase activities increased in autotrophic and acetate-containing cultures. Citrate lyase activity was higher than ATP citrate synthase activity in autotrophic cultures. These data suggest that citrate lyase and AMP-forming acetate:CoA ligase, but not ATP citrate synthase, work opposite citrate synthase to control the direction of carbon flow in the citric acid cycle.
...
PMID:Citric acid cycle in the hyperthermophilic archaeon Pyrobaculum islandicum grown autotrophically, heterotrophically, and mixotrophically with acetate. 1674 Sep 41

The purpose of this study was to investigate variations in hepatic regulation of metabolism during the dry period, after parturition, and in early lactation in dairy cows. For this evaluation, cows were divided into 2 groups based on the plasma concentration of beta-hydroxybutyric acid (BHBA) in wk 4 postpartum (PP; group HB, BHBA >0.75 mmol/L; group LB, BHBA <0.75 mmol/L, respectively). Liver biopsies were obtained from 28 cows at drying off (mean 59 +/- 8 d antepartum), on d 1, and in wk 4 and 14 PP. Blood samples were collected every 2 wk during this entire period. Liver samples were analyzed for mRNA abundance of genes related to carbohydrate metabolism (pyruvate carboxylase, PC; phosphoenolpyruvate carboxykinase, PEPCK; citrate synthase, CS), fatty acid biosynthesis (ATP citrate lyase, ACLY) and oxidation (acyl-CoA synthetase long-chain, ACSL; carnitine palmitoyltransferase 1A, CPT 1A; carnitine palmitoyltransferase 2, CPT 2; acyl-coenzyme A dehydrogenase very long chain, ACADVL), cholesterol biosynthesis (3-hydroxy-3-methylglutaryl-coenzyme A synthase 1, HMGCS1), ketogenesis (3-hydroxy-3-methylglutaryl-coenzyme A synthase 2, HMGCS2), and of genes encoding the transcription factors peroxisome proliferator-activated receptor alpha (PPARalpha), peroxisome proliferator-activated receptor gamma (PPARgamma), and sterol regulatory element binding factor 1 (SREBF1). Blood plasma was assayed for concentrations of glucose, BHBA, nonesterified fatty acids, cholesterol, triglycerides, insulin, insulin-like growth factor-I, and thyroid hormones. In both groups, plasma parameters followed a pattern usually observed in dairy cows. However, changes were moderate and the energy balance in cows turned positive in wk 7 PP for both groups. Additionally, the energy balance and milk yield were similar for both groups after parturition onwards. Significant group effects were found at drying off, when plasma concentrations of triglycerides were higher in LB than in HB, and in wk 4 PP, when plasma concentrations of glucose and IGF-I were lower in HB than in LB. Similarly, moderate changes in mRNA expression of hepatic genes between the different time points were observed, although HB cows showed more adaptive performance than LB cows based on changes in mRNA expression of PEPCKc, PEPCKm, CS, CPT 1A, CPT 2, and PPARalpha. Part of the variation measured in this study was explained by parity. Significant Spearman rank correlation coefficients between the variables were not similar at each time point and were not similar between the groups at each time point, suggesting that metabolic regulation differs between cows. In conclusion, metabolic regulation in dairy cows is a dynamic system, and differs obviously between cows at different metabolic stages related to parturition.
...
PMID:Variation in hepatic regulation of metabolism during the dry period and in early lactation in dairy cows. 1938 50

Heliobacteria are a group of anoxygenic phototrophs that can grow photoheterotrophically in defined minimal media on only a limited range of organic substrates as carbon sources. In this study the mechanisms which operate to assimilate carbon and the routes employed for the biosynthesis of cellular intermediates were investigated in a newHeliobacterium strain, HY-3. This was achieved using two approaches (1) by measuring the activities of key enzymes in cell-free extracts and (2) by the use of(13)C nuclear magnetic resonance (NMR) spectroscopy to analyze in detail the labelling pattern of amino-acids of cells grown on [(13)C] pyruvate and [(13)C] acetate.Heliobacterium strain HY-3 was unable to grow autotrophically on CO2/H2 and neither (ATP)-citrate lyase nor ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBPcase) were detectable in cell-free extracts. The enzyme profile of pyruvate grown cells indicated the presence of a pyruvate:acceptor oxidoreductase at high specific activity which could convert pyruvate to acetyl-Coenzyme A. No pyridine nucleotide dependent pyruvate dehydrogenase complex activity was detected. Of the citric-acid cycle enzymes, malate dehydrogenase, fumarase, fumarate reductase and an NADP-specific isocitrate dehydrogenase were readily detectable but no aconitase or citrate synthase activity was found. However, the labelling pattern of glutamate in long-term 2-[(13)C] acetate incorporation experiments indicated that a mechanism exists for the conversion of carbon from acetyl-CoA into 2-oxoglutarate. A 2-oxoglutarate:acceptor oxidoreductase activity was present which was also assayable by isotope exchange, but no 2-oxoglutarate dehydrogenase complex activity could be detected. Heliobacteria appear to use a type of incomplete reductive carboxylic acid pathway for the conversion of pyruvate to 2-oxoglutarate but are unable to grow autotrophically using this metabolic route due to the absence of ATP-citrate lyase.
...
PMID:An enzyme and(13)C-NMR study of carbon metabolism in heliobacteria. 2431 15


<< Previous 1 2 3 Next >>

---