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)

Commonly the TCA cycle fulfils an anabolic and a catabolic function in case of aerobic chemoorganoheterotrophic nutrition. In methylotrophic growth the TCA cycle is dispensable as a bioenergetic pathway. This is reflected by properties of citrate synthase in facultative methylotrophic bacteria. Two citrate synthases, a "chemoorganoheterotrophic" one, which is inhibited by NADH (or ATP in Acetobacter MB 58), and a "methylotrophic" one, which is not or less affected by energy indicators, were found in Pseudomonas oleovorans, Pseudomonas MS, Pseudomonas MA, and Acetobacter MB 58. The concentration of these citrate synthases depends on the manner of nutrition. Bacteria with ICL-negative-variant of the serine pathway and with ribulosebisphosphate pathway seem to possess only a "chemoorganoheterotrophic" citrate synthase. Possibly the anabolic function of this citrate synthase can be realized by metabolites.
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PMID:[Regulation of citrate synthase in facultative methylotrophic bacteria]. 688 Feb 50

Adenine nucleotides were tested as effectors of peroxisomal and mitochondrial citrate synthase from Agave americana leaves in the presence of different concentrations of acetyl-CoA and oxalacetate substrates. ATP inhibited both enzyme activities but with a different inhibition profile. 1.0-7.5 mM ADP did not inhibit the peroxisomal citrate synthase in the presence of high substrate concentrations, while the mitochondrial enzyme was strongly inhibited by 1.0 mM ADP in the same conditions. Likewise, a different pattern was obtained with AMP on both peroxisomal and mitochondrial activities. The rate of citrate formation as function of acetyl-CoA and oxalacetate concentration was also studied in both fractions. Maximal velocity was highest in the peroxisomal fraction, whether acetyl-CoA or oxalacetate were the variable substrates. These differences indicate that peroxisomal and mitochondrial citrate synthases seem to be two different isoenzymes.
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PMID:Properties of peroxisomal and mitochondrial citrate synthase from Agave americana. 715 52

Citrate synthase (citrate oxaloacetate-lyase (pro-3S-CH2cOO leads to acetate-CoA), EC 4.1.3.7) was purified 66-fold from cell-free extracts of a citric acid producing strain of Aspergillus niger. The enzyme is labile at low ionic strength, but can effectively be stabilized by K+, oxaloacetate or glycerol. It has a molecular weight of 80 000 and an optimum pH of 8.5. The enzyme is activated by monovalent cations in dilute buffer solutions, and inhibited by Mg2+ independent of the buffer molarity. Kinetic analysis indicated that the reaction proceeds by an ordered sequential mechanism. The Michaelis constants are: 5 microM for oxaloacetic acid at all concentrations of acetyl-CoA; 10 microM for acetyl-CoA at infinite concentrations of oxaloacetate. Coenzyme A is inhibitory, being competitive with acetyl-CoA (Ki = 0.15 mM) and non-competitive with oxaloacetate. Citrate has no effect. Among various metabolites tested, only ATP can inhibit the enzyme. The inhibition is competitive with acetyl-CoA (Ki = 1.0 mM), and non-competitive with oxaloacetate. Mg2+ partially relieves this inhibition. Other adenine nucleotides are also inhibitory, but to a lesser extent. It is proposed that citrate synthase from Aspergillus niger is only weakly regulated, its activity being mainly controlled by oxaloacetate availability.
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PMID:Regulation of citrate synthase from the citric acid-accumulating fungus, Aspergillus niger. 741 57

Citrate synthase catalyses the initial reaction of the citric acid cycle and can therefore be considered as the rate-controlling enzyme for the entry of substrates into the cycle. In Corynebacterium glutamicum, the specific activity of citrate synthase was found to be independent of the growth substrate and of the growth phase. The enzyme was not affected by NADH or 2-oxoglutarate and was only weakly inhibited by ATP (apparent Ki = 10 mM). These results suggest that in C. glutamicum neither the formation nor the activity of citrate synthase is subject to significant regulation. The citrate synthase gene, gltA, was isolated, subcloned on plasmid pJC1 and introduced into C. glutamicum. Relative to the wild-type the recombinant strains showed six- to eightfold higher specific citrate synthase activity. The nucleotide sequence of a 3007 bp DNA fragment containing the gltA gene and its flanking regions was determined. The predicted gltA gene product consists of 437 amino acids (M(r) 48,936) and shows up to 49.7% identity with citrate synthase polypeptides from other organisms. Inactivation of the chromosomal gltA gene by gene-directed mutagenesis led to absence of detectable citrate synthase activity and to citrate (or glutamate) auxotrophy, indicating that only one citrate synthase is present in C. glutamicum. Transcriptional analysis by Northern (RNA) hybridization and primer extension experiments revealed that the gltA gene is monocistronic (1.45 kb mRNA) and that its transcription initiates at two consecutive G residues located 121 and 120 bp upstream of the translational start.
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PMID:Nucleotide sequence, expression and transcriptional analysis of the Corynebacterium glutamicum gltA gene encoding citrate synthase. 752 44

The effect of 6-week endurance training on mitochondrial ATP production rate was investigated in 14 elderly men. Mean age, body weight and height were 63 +/- 6 yr, 75.6 +/- 9.2 kg and 174 +/- 4 cm, respectively. Subjects trained on a Monark cycle ergometer at 79 +/- 8% of their maximal heart rate for 1 h day-1, 4 days week-1. Muscle samples were obtained at rest, before and after endurance training, by a needle biopsy technique and used for determination of mitochondrial ATP production rate in isolated mitochondria and enzyme assays. Endurance training resulted in a significant increase in maximal oxygen uptake (L min-1) (P < 0.01). Citrate synthase activity, a mitochondrial marker enzyme, and hexokinase activity increased significantly (both P < 0.01) in response to training while 3-hydroxyacyl-CoA dehydrogenase and carnitine palmitoyltransferase I activities remained statistically unchanged. A higher mitochondrial ATP production rate was observed after endurance training with the substrate combinations pyruvate+palmitoyl-L-carnitine+L-glutamate+malate (P < 0.01), L-glutamate (P < 0.001), pyruvate+malate (P < 0.05) and palmitoyl-L-carnitine+malate (P < 0.01). The largest increase was obtained with L-glutamate (170%). Significant correlations were observed between the percent increase in citrate synthase activity and those of mitochondrial ATP production rates. It was concluded that the increased mitochondrial ATP production rate of aged human skeletal muscle with training seems mainly to occur through an increased mitochondrial content, and in a way similar to those observed in young men.
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PMID:Mitochondrial ATP production rate in 55 to 73-year-old men: effect of endurance training. 757 22

RNAs of Rickettsia prowazekii, an obligate intracytoplasmic bacterium, have been identified and analyzed by an RNase protection assay. Total RNA, a mixture of host cell RNA and rickettsial RNA, was isolated from rickettsia-infected mouse L929 cells by the hot-phenol method. After hybridization with specific antisense RNA probes and digestion with RNase, the protected products were analyzed by electrophoresis and autoradiography. The results show that there is only one mRNA species for the ATP/ADP translocase gene (tlc) but two mRNA species for the citrate synthase gene (gltA). RNA half-lives were determined by measuring the RNA remaining after addition of rifampin. The half-lives of tlc mRNA, gltA mRNA I, and gltA mRNA II in R. prowazekii are 8.4 +/- 0.6, 12.3 +/- 1.3, and 20.5 +/- 1.8 min, respectively. However, the half-lives of tlc mRNA and gltA mRNA I in recombinant Escherichia coli strains are 2.9 +/- 0.1 and 1.4 +/- 0.1 min, respectively. The 16S rRNA in R. prowazekii was also examined and shown to be stable.
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PMID:Identification of tlc and gltA mRNAs and determination of in situ RNA half-life in Rickettsia prowazekii. 769 26

At normal temperatures, Hsp90 is one of the most abundant proteins in the cytosol of various eucaryotic cells. Upon heat shock, the level of Hsp90 is increased even more, suggesting that it is important for helping cells to survive under these conditions. However, studies so far have been almost exclusively concerned with the function of Hsp90 under non-stress conditions, and therefore only little is known about the role of Hsp90 during heat shock. As a model for heat shock in vitro, we have monitored the inactivation and subsequent aggregation of dimeric citrate synthase (CS) at elevated temperatures. Hsp90 effectively "stabilized" CS under conditions where the enzyme is normally inactivated and finally aggregates very rapidly. A kinetic dissection of the unfolding pathway of CS succeeded in revealing two intermediates which form and subsequently undergo irreversible aggregation reactions. Hsp90 apparently interacts transiently with these highly structured early unfolding intermediates. Binding and subsequent release of the intermediates favorably influences the kinetic partitioning between two competing processes, the further unfolding of CS and the productive refolding to the native state. As a consequence, CS is effectively stabilized in the presence of Hsp90. The significance of this interaction is especially evident in the suppression of aggregation, the major end result of thermal unfolding events in vivo and in vitro. These effects, which are ATP-independent, seem to be a general function of members of the Hsp90 family, since yeast and bovine Hsp90 as well as the Hsp90 homologue from Escherichia coli gave similar results. It seems likely that this function also reflects the role of Hsp90 under heat shock conditions in vivo. We therefore propose that members of the Hsp90 family convey thermotolerance by transiently binding to highly structured early unfolding intermediates, thereby preventing their irreversible aggregation and stabilizing the active species.
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PMID:Transient interaction of Hsp90 with early unfolding intermediates of citrate synthase. Implications for heat shock in vivo. 770 69

Plants synthesize several classes of small heat shock proteins ranging in size from 15 to 30 kDa. Two conserved classes, designated class I and class II, are localized to the cytosol. Recombinant HSP18.1 and HSP17.7, representing class I and class II proteins from pea, respectively, were expressed in Escherichia coli and purified. Non-denaturing polyacrylamide gel electrophoresis and electron microscopy demonstrated that the purified proteins formed discretely sized, high molecular weight complexes. Sedimentation equilibrium analytical ultracentrifugation revealed that the HSP18.1 and HSP17.7 complexes were composed of approximately 12 subunits. Both proteins were able to enhance the refolding of chemically denatured citrate synthase and lactate dehydrogenase at stoichiometric levels in an ATP-independent manner. Furthermore, HSP18.1 and HSP17.7 prevented aggregation of citrate synthase at 45 degrees C and irreversible inactivation of citrate synthase at 38 degrees C. HSP18.1 also suppressed aggregation of lactate dehydrogenase at 55 degrees C. These findings demonstrate that HSP18.1 and HSP17.7 can function as molecular chaperones in vitro.
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PMID:Structure and in vitro molecular chaperone activity of cytosolic small heat shock proteins from pea. 773 77

The postnatal development of the complexes of the electron transport chain in isolated rat brain mitochondria were investigated. Nonsynaptosomal brain mitochondria were isolated from rats aged 1-60 days, and the activities of mitochondrial complexes I, II-III, IV, V and citrate synthase were measured. There was a significant increase in the activity of complex I from postnatal day 1 to day 21, and in the activities of complex II-III, complex IV and citrate synthase from postnatal day 1 to day 60. In contrast, the activity of complex V increased significantly between postnatal day 1 and day 10 where it attained adult levels. These data are consistent with the increasing demand for mitochondrial ATP production as the brain develops and as aerobic glycolysis becomes the major pathway for energy production.
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PMID:Postnatal development of the complexes of the electron transport chain in isolated rat brain mitochondria. 776 12

Idiopathic dilated cardiomyopathy is associated with derangement of myocardial sarcoplasmic Ca-homeostasis and energy production. The molecular mechanism for these changes is unknown. Accordingly, we used genetic and experimentally-induced models of canine dilated cardiomyopathy and tested the hypothesis that these metabolic changes resulted from altered gene expression, as indicated by mRNA content. We studied dilated cardiomyopathy occurring naturally (n = 9) in Doberman pinschers, and in dogs subjected to rapid ventricular pacing (n = 5), in comparison with normal dogs (n = 9). We determined content and integrity of mRNA's using Northern and slot blotting, and measured activities of their translated product for the Ca-release channel and Ca-ATPase of sarcoplasmic reticulum, lactate dehydrogenase of glycolysis, citrate synthase of the tricarboxylic acid cycle, and for myoglobin, ATP-synthetase and the adenine nucleotide transporter, which are integral in oxidative phosphorylation. We found that, whereas both mRNA content and enzyme activity for markers of Ca-cycling, glycolysis, and oxidative phosphorylation were downregulated (20-80%) in dilated cardiomyopathy, they were upregulated (10-15%) for tricarboxylic acid cycling and for ribosomal RNA. RNA from cardiomyopathic tissue was up to 50% more degraded than for normal hearts in association with a 150% increase in ribonuclease activity. Downregulation of the Ca-cycle was asymmetric, with the Ca-channel being 65% more affected than the Ca-ATPase. This work supports the general paradigm that transcriptional and translational responses to pathophysiology are major determinants of the metabolic response seen in cardiac failure.
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PMID:Myocardial mRNA content and stability, and enzyme activities of Ca-cycling and aerobic metabolism in canine dilated cardiomyopathies. 777 66


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