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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)

Azotobacter beijerinckii was grown in ammonia-free glucose/mineral salts media in chemostat culture under oxygen or nitrogen limitation. Selected enzymes of the tricarboxylic acid cycle and poly-beta-hydroxybutyrate metabolism were monitored in relation to oxygen supply for both steady and transition states. Two dissolved oxygen concentrations were used for the nitrogen-limited steady state to investigate the possible effects of respiratory protection of nitrogenase on these enzymes. The levels of NADH oxidase, isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase increased markedly on relaxation of oxygen limitation while pyruvate dehydrogenase and citrate synthase were relatively unaffected. beta-Ketothiolase and acetoacetyl-CoA reductase levels decreased as oxygen limitation was relaxed. Respiratory activity, as measured by the QO2 value, increased with oxygen supply rate. Imposition of oxygen limitation on a nitrogen-limited culture caused an immediate increase in the NADH/NAD ratio but this rapidly readjusted to its previous steady-state value. These changes are discussed in relation to respiratory protection of nitrogenase and poly-beta-hydroxybutyrate metabolism in A. beijerinckii.
J Gen Microbiol 1976 Dec
PMID:Regulation of the tricarboxylic acid cycle and poly-beta-hydroxybutyrate metabolism in Azotobacter beijerinckii grown under nitrogen or oxygen limitation. 1 43

2-Methylcitrate was tested in vitro on enzymes which interact with citrate and isocitrate. It was found to inhibit citrate synthase, aconitase, the NAD+- and NADP+-linked isocitrate dehydrogenase. This inhibition was competitive in nature except in the case of aconitase, and the Ki for all the enzymes was in the range of 1.5-7.6 mM. Phosphofructokinase was also inhibited by 2-methylcitrate with 50% inhibition achieved at 1 mM. ATP-citrate lyase and acetyl-CoA carboxylase were not inhibited by this compound. 2-Methylcitrate was not a substrate for ATP-citrate lyase. Acetyl-CoA carboxylase was activated by 2-methylcitrate with a Ka of 2.8 mM. The apparent Km (3.3 mM) for 2-methylcitrate for the mitochondrial citrate transporter was about 10-fold higher than the apparent Km (0.26 mM) for citrate. The tricarboxylase carrier can also be inhibited by low concentrations (0.2 mM) of 2-methylcitrate when the concentration of citrate is close to the apparent Km. Accumulation of 2-methylcitrate inside the mitochondrion, therefore, might lead to inhibition of enzymes in the citric acid cycle and thereby contribute to the ketogenesis and hypoglycemia seen under these conditions.
Pediatr Res 1975 Dec
PMID:Effect of 2-methylcitrate on citrate metabolism: implications for the management of patients with propionic acidemia and methylmalonic aciduria. 12 73

The metabolic effects on rat cardiac and skeletal muscle of a strenous program of swimming, of cold acclimation and of isoprenaline treatment (0.3 mg/kg daily for 5 five-day weeks) were compared. Exercised and cold-exposed rats gained less body weight than did controls or isoprenaline-treated rats. In all treated groups the heart and the intercapular brown adipose tissue hypertrophied. The size of the adrenals increased only in isoprenaline-treated animals. Cold-acclimation and physical training increased and isoprenaline treatment reduced or did not affect the activities of succinate dehydrogenase, malate dehydrogenase and citrate synthase of cardiac muscle. In the skeletal muscle all treatments resulted in increased activities of these enzymes. Of the anaerobic enzymes analysed, only the activity of hexokinase increased in response to the treatements used. This increase was the same in cardiac as in skeletal muscle, but it was significantly greater with isoprenaline-treatment than with training or with cold-acclimation. The activities of lactate dehydrogenase and phosphofructokinase did not differ significantly. All treatments improved cold resistance, but only swimming exercise and cold acclimation significantly increased tolerance to exercise. It is concluded that prolonged stimulation of adrenergic beta-receptors by catecholamines is responsible for the metabolic changes observed.
Acta Physiol Scand 1975 Dec
PMID:Comparison of the effects of physical exercise, cold acclimation and repeated injections of isoprenaline on rat muscle enzymes. 12 87

The modification of Escherichia coli citrate synthase (citrate oxaloacetatelyase(pro-3S-CH2.COO- leads to acetyl-CoA, EC 4.1.3.7) with 5,5'-dithiobis-(2-nitrobenzoic acid) has been investigated. (1) In low ionic strength (20 mM Tris.HCl, pH 8.0): (A) Eight thiol groups per tetramer of the native enzyme reacted with Nbs2. (b) Two of the eight accessible thiols were modified rapidly with the loss of 26% enzyme activity but with no change in the NADH inhibition. The remaining six were modified more slowly, resulting in a further 60% loss of activity and complete densensitization to NADH. (c) The 2nd-order rate constant for the modification of the rapidly reacting thiols is 2.5.10(4) M-1.min-1. At the reagent concentrations used (0.1 to 0.2 mM) the modification of the six thiols in the slow kinetic set appeared to be 1st-order; at 0.1 mM dithionitrobenzoic acid their rate of modification was approximately 30 times slower than the thiols in the fast kinetic set. (2) In high ionic strength (20 mM Tris.HCl, pH 8.0, 0.1 M KCl): (a) Four thiol groups were modified in a single kinetic set and it appeared that these thiols are four of the six slowly modified in the absence of KCl. (b) The modification resulted in 70% loss of enzyme activity and complete loss of NADH inhibition. (3) From the kinetic analysis it is proposed that the four thiol groups accessible to dithionitrobenzoic acid in the absence and presence of 0.1 M KCl are those involved in the response of NADH. Modification of any one of these four groups produced no reduction in the inhibition; instead, loss of NADH sensitivity was coincident with the appearance of tetrameric protein possessing three substituted thiols, whereas enzyme with one or two modified groups was still fully inhibited by NADH.
Biochim Biophys Acta 1977 Dec 08
PMID:Thiol groups of Escherichia coli citrate synthase and their influence on activity and regulation. 20 Feb 73

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.
J Clin Endocrinol Metab 1977 Dec
PMID:The clinical and biochemical implications of pyruvate carboxylase deficiency. 41 60

A panel of twenty independently derived clones of man-mouse somatic cell hybrids isolated from fusions involving eight different parent cell combinations simultaneously analyzed for human chromosomes, citrate synthase, and a large number of other enzyme markers firmly or tentatively assigned to individual human chromosomes have provided direct evidence for a firm assignment of the structural gene coding for citrate synthase (CS) to human chromosome 12.
Hum Genet 1977 Dec 23
PMID:Direct assignment of citrate synthase (CS) gene to human chromosome 12 in man-mouse somatic cell hybrids. 59 42

Enterobacter aerogenes was grown in continous culture with ammonia as the growth-limiting substrate, and changes in citrate lyase and citrate synthase activities were monitored after growth shifts from anaerobic growth on citrate to aerobic growth on citrate, aerobic growth on glucose, anaerobic growth on glucose, and anaerobic growth on glucose plus nitrate. Citrate lyase was inactivated during aerobic growth on glucose and during anaerobic growth with glucose plus nitrate. Inactivation did not occur during anaerobic growth on glucose, and as a result of the simultaneous presence of citrate lyase and citrate synthase, growth difficulties were observed. Citrate lyase inactivation consisted of deacetylation of the enzyme. The corresponding deacetylase could not be demonstrated in cell extracts, and it is concluded that, as in a number of other inactivations, electron transport to oxygen or nitrate was required for inactivation.
J Bacteriol 1977 Dec
PMID:Energy-dependent inactivation of citrate lyase in Enterobacter aerogenes. 92 71

Two populations of mitochondria were observed upon ultrastructural examination of cardiac muscle tissue, one located directly beneath the sarcolemma (subsarcolemmal mitochondria) and another between the myofibrils (interfibrillar mitochondria). Subsarcolemmal mitochondria were released by treatment of heart muscle with a Polytron tissue processor, while interfibrillar mitochondria were released by nagarse digestion of the remaining tissue. These results were supported by electron microscopy of Polytron-treated heart tissue showing rupture and loss of sarcolemma with release of the underlying mitochondria but with retention of intact mitochondria between the myofibrils. Electron microscopy of the isolated mitochondria indicated that both mitochondrial types maintained their structural integrity throughout the isolation procedure. Specific activities of succinate dehydrogenase and citrate synthase were higher in the interfibrillar mitochondria as compared to the subsarcolemmal mitochondria, while those of carnitine palmitoyltransferase and alpha-glycerophosphate dehydrogenase were nearly the same in both. Interfibrillar mitochondria oxidized all substrates tested approximately 1.5 times faster than did the subsarcolemmal mitochondria. Thus the two mitochondrial types differed not only in their respective locations in the cell, but also in certain biochemical properties.
J Biol Chem 1977 Dec 10
PMID:Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle. 92 18

The NH2 terminus of ovalbumin is acetylated in cell-free protein-synthesizing systems as it is in vivo. The acetyl group is derived from acetyl-CoA and it is incorporated during translation. Acetylation can be prevented by metabolizing the available acetyl-CoA to citrate with the addition of citrate synthase and oxalacetate to the translation system. The NH2 terminus of ovalbumin synthesized under these conditions can be sequenced by automated Edman degradation. This procedure has also been applied to the sequencing of Pr 76gag, the viral core protein precursor synthesized from 35 S Rous sarcoma virus RNA.
J Biol Chem 1977 Dec 25
PMID:Prevention of NH2-terminal acetylation of proteins synthesized in cell-free systems. 92 22

Fatty acyl-CoAs are good detergents (dritical micelle concentrations = 3-4 muM) and can inhibit a number of enzymes, including some involved in fatty acid biosynthesis. The regulatory significance of fatty acyl-CoAs as negative effectors has been questioned largely because of the difficulties in distinguishing possible nonspecific detergent effects from more specific regulatory interactions with these enzymes. A new analogue of oleoyl-CoA, oleoyl-(1, N6-etheno)-CoA, is a better detergent (critical micelle concentration = 3.2 muM) than oleoyl-CoA (critical micelle concentration = 4.7 muM). This new analogue is not as good (by an order of magnitude) an inhibitor of citrate synthase [citrate oxaloacetatelyase (pro-3S-CH2-COO-vectoracetyl-CoA); EC 4.1.3.7] nor is it bound as well oleoyl-CoA. Since the only difference between these two compounds is substitution of 1,N6-ethenoadenine for the adenine of CoA, the difference in inhibition and binding implies a specific interaction between the adenine moiety of oleoyl-CoA and citrate synthase. Moreover, since oleoyl-(1,N6-etheno)CoA is a better detergent than oleoyl-CoA, the detergency of oleoyl-CoA is not the sole cause of the fatty acyl-CoA inhibition of citrate synthase. These results support a physiological role for oleoyl-CoA as a negative effector for citrate synthase. An analogous physiological role for fatty acyl-CoA as negative effectors for other enzymes seems reasonable.
Proc Natl Acad Sci U S A 1975 Dec
PMID:Inhibition of citrate synthase by oleoyl-CoA: a regulatory phenomenon. 106 Oct 66


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