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At least 721 records · Page 40Linked to original sources
PubMed1988

Structural beta-cell changes and transient hyperglycemia in mice treated with compounds inducing inhibited citric acid cycle enzyme activity.

An initial transient hyperglycemia was seen in mice injected with asparagine, fluoroacetate, hydroxylamine, or malonate plus methionine, whereas an initial triphasic blood glucose response and a transient "secondary" hyperglycemia were exhibited in those injected with hydroxylamine plus arsenite, and a delayed hypoglycemia was observed in those treated with fluoroacetate or arsenite. The glucose-induced insulin secretion was significantly decreased in isolated pancreatic islets incubated with hydroxylamine plus arsenite. Light and electron microscopy, pyroantimonate technique, and X-ray microanalysis disclosed mitochondrial damage, degeneration, and necrosis among the beta-cells in the islets of mice injected with hydroxylamine plus arsenite. Glycogen depletion and microvesicular fatty change were seen in the liver of mice treated with fluoroacetate, arsenite, or hydroxylamine plus arsenite. These observations support the view that inhibition of the activity of citric acid cycle enzymes and associated reactions in the beta-cells play a role in the induction of diabetic features.

Animals↗
PubMed2000

Functions of the membrane-associated and cytoplasmic malate dehydrogenases in the citric acid cycle of Corynebacterium glutamicum.

Like many other bacteria, Corynebacterium glutamicum possesses two types of L-malate dehydrogenase, a membrane-associated malate:quinone oxidoreductase (MQO; EC 1.1.99.16) and a cytoplasmic malate dehydrogenase (MDH; EC 1.1.1.37) The regulation of MDH and of the three membrane-associated dehydrogenases MQO, succinate dehydrogenase (SDH), and NADH dehydrogenase was investigated. MQO, MDH, and SDH activities are regulated coordinately in response to the carbon and energy source for growth. Compared to growth on glucose, these activities are increased during growth on lactate, pyruvate, or acetate, substrates which require high citric acid cycle activity to sustain growth. The simultaneous presence of high activities of both malate dehydrogenases is puzzling. MQO is the most important malate dehydrogenase in the physiology of C. glutamicum. A mutant with a site-directed deletion in the mqo gene does not grow on minimal medium. Growth can be partially restored in this mutant by addition of the vitamin nicotinamide. In contrast, a double mutant lacking MQO and MDH does not grow even in the presence of nicotinamide. Apparently, MDH is able to take over the function of MQO in an mqo mutant, but this requires the presence of nicotinamide in the growth medium. It is shown that addition of nicotinamide leads to a higher intracellular pyridine nucleotide concentration, which probably enables MDH to catalyze malate oxidation. Purified MDH from C. glutamicum catalyzes oxaloacetate reduction much more readily than malate oxidation at physiological pH. In a reconstituted system with isolated membranes and purified MDH, MQO and MDH catalyze the cyclic conversion of malate and oxaloacetate, leading to a net oxidation of NADH. Evidence is presented that this cyclic reaction also takes place in vivo. As yet, no phenotype of an mdh deletion alone was observed, which leaves a physiological function for MDH in C. glutamicum obscure.

Cell Membrane↗
PubMed1996

Anterior tongue stimulation with amiloride suppresses NaCl saltiness, but not citric acid sourness in humans.

Suppression of the saltiness of NaCl solutions by amiloride, a sodium channel blocker, has previously been reported a number of times in humans. This suppression was seen with techniques that involved stimulation of small areas of the tongue. It was not certain, however, whether amiloride would suppress saltiness with stimulation of a much larger area of the tongue; one published study, in fact, found negative results with whole mouth stimulation. For this study, eight subjects dipped a large part of the anterior portion of the tongue into a 10-ml sample of NaCl solution, or a NaCl and amiloride solution, and reported its magnitude of saltiness intensity. The results show that amiloride suppressed the saltiness of NaCl when a large area of the anterior tongue was stimulated. Consistent with previous studies, there was individual variability across subjects in this suppressive effect of amiloride. This study also used this method to test the effects of amiloride on the sourness of citric acid, which was not expected to be affected. No suppression of sourness was seen with amiloride.

Adolescent↗
PubMed1984

Defects in citric acid cycle and the electron transport chain in progressive poliodystrophy.

We will present 8 children with progressive infantile or juvenile poliodystrophy (Alpers' disease), associated with a defect in pyruvate metabolism. Laboratory studies showed elevated levels of lactate in CSF and, in 4 children, elevated levels in serum. Histopathologic studies revealed lipid storage in liver and/or muscle tissue, sometimes myopathy with abnormal mitochondria and slight axonal degeneration in the peripheral nerve. Autopsy showed the characteristics of progressive poliodystrophy with degeneration and loss of neurons. Electron microscopy of cerebral cortex showed no mitochondrial abnormalities in neurons or astroglia. Biochemical studies in muscle and/or liver and/or cerebral tissue showed different deficiencies in pyruvate metabolism: in the pyruvate dehydrogenase complex, in the second part of the citric acid cycle (after the oxoglutarate dehydrogenase complex), in the NADH oxidation, in cytochrome aa3 and in pyruvate carboxylase.

Adolescent↗
PubMed1991

Sensitivity of ketogenesis and citric acid cycle to stevioside inhibition of palmitate transport across the cell membrane.

The effect of stevioside, an inhibitor of long-chain fatty acid transport, on ketogenesis and on [14C]CO2 production from [1-14C]palmitate (100-300 microM) was investigated in the isolated and hemoglobin-free perfused rat liver. Stevioside (2.5 mM), a sweet glycoside found in Stevia rebaudiana leaves, inhibited both parameters, but had a lower effect on [14C]CO2 production. At 300 microM palmitate and 150 microM albumin, for example, ketogenesis was inhibited by 66.3%, whereas no significant inhibition of [14C]CO2 was demonstrable. These results were interpreted to reflect 1) different degrees of saturation of the citric acid cycle and the ketogenic pathway and 2) changes in the redox state of the mitochondrial NAD(+)-NADH couple which may also occur upon stevioside infusion.

Animals↗
PubMed1969

Control of the citric acid cycle by glyoxylate. The mechanism of inhibition of oxoglutarate dehydrogenase, isocitrate dehydrogenase and aconitate hydratase.

1. The effects of glyoxylate on partially purified preparations of aconitate hydratase, isocitrate dehydrogenase and oxoglutarate dehydrogenase were compared with those of oxalomalate and hydroxyoxoglutarate (obtained by condensation of glyoxylate with oxaloacetate and pyruvate respectively). 2. Glyoxylate (1mm) did not affect aconitate hydratase and isocitrate dehydrogenase, whereas oxalomalate (1mm) inhibited the enzyme activities completely. 3. Glyoxylate (0.025mm) inhibited oxoglutarate dehydrogenase irreversibly, whereas the same concentrations of oxalomalate and hydroxyoxoglutarate were ineffective. This inhibitory effect was prevented if oxoglutarate, pyruvate or oxaloacetate was mixed with the enzyme before the glyoxylate. 4. Incubation of oxoglutarate dehydrogenase with radioactive glyoxylate produced radioactive carbon dioxide; radioactivity was also recovered in the portion of the enzyme identified with thiamin pyrophosphate. 5. The behaviour of glyoxylate in producing multiple inhibitions of the citric acid cycle, either by direct interaction with oxoglutarate dehydrogenase, or by means of its condensation compounds which inhibit aconitate hydratase and isocitrate dehydrogenase, is discussed.

Animals↗
PubMed1992

Correlation of biological value of feed phosphates with their solubility in water, dilute hydrogen chloride, dilute citric acid, and neutral ammonium citrate.

Relative biological values (BV) of 36 feed phosphates were determined with female turkeys in bioassays of 21-day duration using three response criteria: weight gain, tibia ash percentage, and gain:feed ratio. Calcium phosphate, dibasic dihydrate (United States Pharmacopeia) was the reference standard. Nine mono-dicalcium phosphates (M-DCP, 21.0% phosphorus), 13 di-monocalcium phosphates (D-MCP, 18.5% phosphorus), and 14 defluorinated phosphates (DFP, 18.0% phosphorus) were evaluated. The average relative BV for M-DCP, D-MCP, and DFP samples were 97.6, 94.6, and 90.8%, respectively. Solubility of phosphates was determined by four recognized methods. The solvents were water, .4% HCl, 2.0% citric acid (CA), and neutral ammonium citrate (NAC). Water solubility of M-DCP samples was greater (67.5%) than that of D-MCP (38.8%) and DFP (8.9%) samples. Correlation of water solubility of phosphates to their relative BV was quite low, and water solubility was a poor indicator of BV. When .4% HCl was the solvent, correlation coefficients (r) were .55, .33, and .72 for M-DCP, D-MCP, and DFP, respectively. Based on these results and prediction equations, .4% HCl solubility would be inappropriate for estimating BV of M-DCP and D-MCP samples. Solubility of feed phosphates (mainly D-MCP and DFP) in 2.0% CA or NAC was positively correlated with BV; the r values were .87 to .95. Both of these solubility tests provided a good index of BV. However, it would seem inappropriate and risky to replace bioassays totally with these tests. Feed phosphate users could perform either the 2.0% CA or NAC solubility test easily as a screen for BV along with other quality control procedures (i.e., phosphorus, calcium, sodium, and fluoride determinations).

Animal Feed↗
PubMed1995

Effect of D- and L-1,3-butanediol isomers on glycolytic and citric acid cycle intermediates in the rat brain.

DL-1,3-butanediol (DL-BD) is an ethanol dimer which affords cerebral protection in various experimental models of hypoxia and ischemia but its mechanism of action is unknown. DL-BD is a ketogenic alcohol and it has been proposed that its protective effect was accomplished through cerebral utilization of ketone bodies. Since DL-BD is a racemic, its metabolic effects could be due to D, L or both isomers. The effects of equimolar doses of DL-, D- and L-BD (25 mmol/Kg) on cerebral metabolism were studied by measuring the cortical levels of the main glycolytic (glycogen, glucose, glucose 6-phosphate, fructose 1,6-diphosphate, pyruvate and lactate) and citric acid cycle (citrate, alpha-ketoglutarate and L-malate) intermediates. The two BD isomers exerted different effects on cerebral metabolism. Unlike L-BD, D- and DL-BD treatments resulted in a slight (+10%) but significant increase in citrate level whereas L-BD treatment led to significant reduction in pyruvate (-12%) and lactate (-24%) levels. These effects were apparently not linked to hyperketonemia, since DL-BHB treatment, which mimicked hyperketonemia induced by DL-BD, had no effect on cerebral metabolites but might be due to intracerebral metabolism of BD.

Animals↗
PubMed1987

Presence and regulation of ATP:citrate lyase from the citric acid producing fungus Aspergillus niger.

ATP:citrate lyase (EC 4.1.3.8) has been identified in cell-free extracts from the filamentous fungus Aspergillus niger. The enzyme was located in the cytosol. It exhibits an activity at least ten times that of acetate-CoA-kinase (EC 6.2.1.1) during growth on carbohydrates as carbon sources, and is thus considered responsible for acetyl-CoA formation under these conditions. It is formed constitutively and its biosynthesis does not appear to be controlled by changes in the nitrogen or carbon source or type. ATP:citrate-lyase appears to be very labile during conventional purification procedures; a method involving fast protein liquid anion exchange chromatography was thus developed in order to obtain enzyme preparations sufficiently free of enzymes which could interfere with kinetic investigations. This preparation displays commonly known characteristics of ATP:citrate lyase with respect to substrate affinities and cofactor requirements, with the exception that the affinity for citrate is rather low (2.5 mM). No activator was found. The enzyme is inhibited by nucleoside diphosphates, nucleoside monophosphates and palmitoyl-CoA. Regulation of ATP:citrate lyase be the energy charge of the cytosol in relation to lipid or citric acid accumulation is discussed in view of these findings.

ATP Citrate (pro-S)-Lyase↗
PubMed1978

Determination of pyruvate oxidation rate and citric acid cycle activity in intact human leukocytes and fibroblasts.

We measured pyruvate oxidation in intact leukocytes and fibroblasts by measuring 14C02 production. The optimal pyruvate concentration appeared to be higher than that usually applied. Activities remained constant during the incubation and were proportional to the amount of tissue protein added. Man values (+/-SD) were 2.8 +/- 0.9 nmol/h per 10(6) cells and 37 +/- 14 nmol/h per mg of protein for leukocytes and fibroblasts, respectively, for [1-14C]pyruvate oxidation; and 2.1 +/- 0.8 nmol/h per 10(6) cells and 18 +/- 7 nmol/h per mg of protein, respectively for [2-14C]pyruvate oxidation. We compared oxidation rates of pyruvate and 2-oxoglutarate by intact cells with those of isolated mitochondria. The ratio of 14CO2 production vs. activity of mitochondrial marker enzyme demonstrated that the rate of pyruvate oxidation can adequately be assayed in intact cells, but that the permeability of the cell membrane is rate-limiting in the oxidation of 2-oxoglutarate. No significant oxidation of other intermediates of the citric acid cycle was found, presumably owing to a low rate of transport of these substances across the cell membrane.

Biological Transport↗
PubMed2004

Hypotensive and toxicological study of citric acid and other constituents from Tagetes patula roots.

Study of the effects of the methanolic extract of Tagetes patula roots on blood pressure led to the isolation of well known citric (1) and malic acid (7) as hypotensive, and pyridine hydrochloride (4) as hypertensive constituents of the plant along with a new constituent, 2-hydroxy, 5-hydroxymethyl furan (9). Citric acid and malic acid caused 71% and 43% fall in Mean Arterial Blood Pressure (MABP) of rats at the doses of 15 mg/kg and 30 mg/kg respectively while pyridine hydrochloride produced 34% rise in the MABP of rats at the dose of 30 mg/kg. LD50 and LD100 of citric acid in mice have been determined as 545 mg/kg and 1000 mg/kg, respectively.

Animals↗
PubMed2000

Functions of the membrane-associated and cytoplasmic malate dehydrogenases in the citric acid cycle of Escherichia coli.

Oxidation of malate to oxaloacetate in Escherichia coli can be catalyzed by two enzymes: the well-known NAD-dependent malate dehydrogenase (MDH; EC 1.1.1.37) and the membrane-associated malate:quinone-oxidoreductase (MQO; EC 1.1.99.16), encoded by the gene mqo (previously called yojH). Expression of the mqo gene and, consequently, MQO activity are regulated by carbon and energy source for growth. In batch cultures, MQO activity was highest during exponential growth and decreased sharply after onset of the stationary phase. Experiments with the beta-galactosidase reporter fused to the promoter of the mqo gene indicate that its transcription is regulated by the ArcA-ArcB two-component system. In contrast to earlier reports, MDH did not repress mqo expression. On the contrary, MQO and MDH are active at the same time in E. coli. For Corynebacterium glutamicum, it was found that MQO is the principal enzyme catalyzing the oxidation of malate to oxaloacetate. These observations justified a reinvestigation of the roles of MDH and MQO in the citric acid cycle of E. coli. In this organism, a defined deletion of the mdh gene led to severely decreased rates of growth on several substrates. Deletion of the mqo gene did not produce a distinguishable effect on the growth rate, nor did it affect the fitness of the organism in competition with the wild type. To investigate whether in an mqo mutant the conversion of malate to oxaloacetate could have been taken over by a bypass route via malic enzyme, phosphoenolpyruvate synthase, and phosphenolpyruvate carboxylase, deletion mutants of the malic enzyme genes sfcA and b2463 (coding for EC 1.1.1.38 and EC 1.1.1.40, respectively) and of the phosphoenolpyruvate synthase (EC 2.7.9.2) gene pps were created. They were introduced separately or together with the deletion of mqo. These studies did not reveal a significant role for MQO in malate oxidation in wild-type E. coli. However, comparing growth of the mdh single mutant to that of the double mutant containing mdh and mqo deletions did indicate that MQO partly takes over the function of MDH in an mdh mutant.

Bacterial Outer Membrane Proteins↗
PubMed1995

Tracing hepatic gluconeogenesis relative to citric acid cycle activity in vitro and in vivo. Comparisons in the use of [3-13C]lactate, [2-13C]acetate, and alpha-keto[3-13C]isocaproate.

The validity of the use of a carbon tracer for investigating liver intermediary metabolism in vivo requires that the labeling pattern of liver metabolites not be influenced by metabolism of the tracer in other tissues. To identify such specific tracer, livers from 48-h starved rats were perfused with recirculating buffer containing [3-13C]lactate, [2-13C]acetate, or alpha-keto[3-13C]isocaproate. Conscious 48-h starved rats were infused with the same tracers for 5 h. The labeling patterns of liver glutamate and extracellular glucose were assayed by gas chromatography-mass spectrometry. In vivo data were corrected for 13CO2 reincorporation into C-1 of glutamate and C-3 and C-4 of glucose, using data from control rats infused with NaH13CO3. With [3-13C]lactate the labeling pattern of liver glutamate was the same in perfused organs and in vivo. In contrast, with [2-13C]acetate and alpha-keto[3-13C]isocaproate the labeling pattern of liver glutamate in vivo was clearly influenced by the expected labeling pattern of citric acid cycle intermediates formed in non-gluconeogenic organs, presumably glutamine made in muscle. Indeed, the labeling pattern of plasma glutamine and liver glutamate were similar in experiments with [3-13C]lactate but different in experiments with [2-13C]acetate and alpha-keto[3-13C]isocaproate. Similar conclusions were drawn from the labeling patterns of glucose. Therefore, labeled lactate appears as the best tracer for studies of liver intermediary metabolism in vivo. Our data also show that a substantial fraction of alpha-ketoisocaproate metabolism occurs in peripheral tissues.

Acetates↗
PubMed1980

Influence of manganese on morphology and cell wall composition of Aspergillus niger during citric acid fermentation.

Morphology and cell wall composition of Aspergillus niger were studied under conditions of manganese sufficient or deficient cultivation in an otherwise citric acid producing medium. Omission of Mn2+ (less than 10(-7) M) from the nutrient medium of Aspergillus niger results in abnormal morphological development which is characterized by increased spore swelling, and squat, bulbeous hyphae. Fractionation and analysis of manganese deficient cell walls revealed increased chitin and reduced beta-glucan contents as well as reduction of galactose containing polymers, as compared to cell walls from manganese sufficient grown hyphae. Addition of copper induced the same effect as manganese deficiency, both on morphology and cell wall composition. Addition of cycloheximide also produced a very similar type of morphology with increased chitin and reduced beta-glucan contents of the cell wall but its effect on galactose was less pronounced.

Amino Acids↗
PubMedDate not supplied

[Content of citric acid and ATP-citrate-lyase activity in tissues of rats with different natural resistance to hypoxic hypoxia].

A significantly lower content of citric acid and a lower ATP-citrate-lyase activity were found in the liver of rats high-resistant to hypoxia as compared to low-resistant ones under conditions of normoxia and after "lifting at a height" of 9000 m. A dependence is supposed to exist between the natural resistance of individuals to hypoxic hypoxia and lipopexia.

ATP Citrate (pro-S)-Lyase↗