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PubMed2004

Equilibrium concentrations for pyruvate dehydrogenase and the citric acid cycle at specified concentrations of certain coenzymes.

It is of interest to calculate equilibrium compositions of systems of biochemical reactions at specified concentrations of coenzymes because these reactants tend to be in steady states. Thermodynamic calculations under these conditions require the definition of a further transformed Gibbs energy G" by use of a Legendre transform. These calculations are applied to the pyruvate dehydrogenase reaction plus the citric acid cycle, but steady-state concentrations of CoA, acetyl-CoA and succinyl-CoA cannot be specified because they are involved in the conservation of carbon atoms. These calculations require the use of linear algebra to obtain further transformed Gibbs energies of formation of reactants and computer programs to calculate equilibrium compositions. At specified temperature, pH, ionic strength and specified concentrations of several coenzymes, the equilibrium composition depends on the specified concentrations of the coenzymes and the initial amounts of reactants.

Citric Acid Cycle↗
PubMed1999

The effect of citric acid, lactic acid, sodium citrate and sodium lactate, alone and in combination with nisin, on the growth of Arcobacter butzleri.

The importance of Arcobacter spp. as a cause of human foodborne illness is unresolved. Organic acids and their sodium salts, and nisin are preservatives commonly used in the type of foods from which the organism is recovered. In this study their effect on the growth of A. butzleri in culture, alone and in combination, was investigated. At 0.5%, 1.0% and 2.0% lactic and citric acids inhibited A. butzleri growth; 2% sodium lactate was effective in inhibiting growth over 8 h incubation but not over longer periods. Sodium citrate was more effective than sodium lactate. Nisin alone inhibited A. butzleri growth at 500 IU ml-1 over 5 h. It did not enhance the effect of sodium citrate inhibition but it did augment the effect of sodium lactate alone over 8 h.

Arcobacter↗
PubMed1982

[Utilization of paraffins and other noncarbohydrate carbon sources for microbial citric acid synthesis].

This article reviews the developments achieved in citrate and isocitrate accumulation with non-carbohydrate substrates by microorganisms presented as well in academic publications as in patients. The efficiency of citrate and isocitrate overproducing microorganisms and of mutants obtained thereof with respect to different carbon sources (n-alkanes, triglycerides, organic acids, etc.) is discussed. The influence of environmental conditions (media, pH etc.) and biochemical mechanisms which lead to metabolic overflow are emphasized. The kinetics of fermentation processes are described, calculations concerning carbon balances are involved. The production of by-products and the conversion of isocitrate to citrate is considered. The production of citric acid by yeasts which utilize different carbon sources may be economically feasible and an accession to the practized molasse-Aspergillus-process.

Aconitate Hydratase↗
PubMedDate not supplied

Assessment of the cough reflex caused by inhalation of sodium lauryl sulfate and citric acid aerosols.

Guinea pigs were exposed for thirty minutes to a particulate aerosol of sodium lauryl sulfate at concentrations of 17.3, 28.9 and 48.6 mg/m3. The exposure chamber in which individual guinea pigs were exposed was fitted with a microphone to record coughing. As the concentration of sodium lauryl sulfate increased, the combined number and severity of the coughs increased and a fade in the response was also observed with exposure duration. Citric acid, a tussigenic agent commonly used to test antitussive agents was also tested using the same experimental protocol and was found to be about an order of magnitude less potent than sodium lauryl sulfate. This model could be useful in assessing the irritating properties of various aerosols to the tracheo-bronchial tree.

Aerosols↗
PubMed2006

Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF.

The stability and transcriptional activity of the hypoxia-inducible factors (HIFs) are regulated by two oxygen-dependent events that are catalyzed by three HIF prolyl 4-hydroxylases (HIF-P4Hs) and one HIF asparaginyl hydroxylase (FIH). We have studied possible links between metabolic pathways and HIF hydroxylases by analyzing the abilities of citric acid cycle intermediates to inhibit purified human HIF-P4Hs and FIH. Fumarate and succinate were identified as in vitro inhibitors of all three HIF-P4Hs, fumarate having K(i) values of 50-80 microM and succinate 350-460 microM, whereas neither inhibited FIH. Oxaloacetate was an additional inhibitor of all three HIF-P4Hs with K(i) values of 400-1000 microM and citrate of HIF-P4H-3, citrate being the most effective inhibitor of FIH with a K(i) of 110 microM. Culturing of cells with fumarate diethyl or dimethyl ester, or a high concentration of monoethyl ester, stabilized HIF-1alpha and increased production of vascular endothelial growth factor and erythropoietin. Similar, although much smaller, changes were found in cultured fibroblasts from a patient with fumarate hydratase (FH) deficiency and upon silencing FH using small interfering RNA. No such effects were seen upon culturing of cells with succinate diethyl or dimethyl ester. As FIH was not inhibited by fumarate, our data indicate that the transcriptional activity of HIF is quite high even when binding of the coactivator p300 is prevented. Our data also support recent suggestions that the increased fumarate and succinate levels present in the FH and succinate dehydrogenase-deficient tumors, respectively, can inhibit the HIF-P4Hs with consequent stabilization of HIF-alphas and effects on tumor pathology.

Cell Line↗
PubMed1981

Topography of root surfaces treated in vitro with citric acid, elastase and hyaluronidase. A scanning electron microscopy study. Part II.

Sixteen extracted human teeth were separated into two groups, root planed, and treated with either elastase or hyaluronidase following acid demineralization. The duration of enzyme application varied from 5 to 20 minutes. From scanning electron micrographs the following was concluded: (1) The cemental collagen network is composed of previously described extrinsic and intrinsic fiber systems. (2) Root planing, using tactile sense as the final criteria, does not always result in complete elimination of contaminants. (3) Citric acid (pH = 1), applied for 3 to 4 minutes, is an effective means of exposing cemental collagen. (4) Qualitatively, the enzyme treatment subsequent to acid demineralization seemed to result in more effective exposure of the collagen mantle of cementum. (5) Further definitive research must be done to determine, both the usefulness of enzymatic treatment in vitro and in vivo and the optimum enzyme concentrations and duration of application.

Adult↗
PubMed1994

Prediction of positional isotopomers of the citric acid cycle: the syntactic approach.

We propose a syntactic approach to modeling of biochemical fluxes that combines a rule-based description of atomic transfer in chemical reactions with a structurally oriented, stochastic model of chemical reaction kinetics. This approach avoids the use of differential equations to describe the production and disappearance of each molecule. The computer simulation predicts the changes over time in the abundance of each positional isotopomer of every metabolic intermediate in the citric acid cycle of heart cells, subsequent to administration of [2-13C]acetate (including natural abundance of 13C). (Positional isotopomers are isomers that differ in the positions of isotopes within the molecule.) The 32 positional isotopomers of glutamate fell into four groups with similar intragroup dynamics but with very different amplitudes. From the relative abundance of each isotopomer of glutamate, we calculate the relative area of multiplets of the nuclear magnetic resonance spectrum.

Acetates↗
PubMed1999

Citric-acid cycle key enzyme activities during in vitro growth and metacyclogenesis of Leishmania infantum promastigotes.

The activities of 5 key regulatory enzymes in most energetic systems, namely citrate synthase (EC 4.1.3.7, CS), NADP-specific isocitrate dehydrogenase (EC 1.1.1.42, ICDH), succinate dehydrogenase (EC 1.3.99.1, SDH), L-malate dehydrogenase (EC 1.1.1.37, MDH), and decarboxylating malic enzyme (EC 1.1.1.40, ME), were measured during the growth and metacyclogenesis of a cutaneous (CL) and a visceral (VL) strain of Leishmania infantum. As occurs with other Leishmania species, infective promastigotes were present along all phases of growth, but their percentages were higher at the early stationary phase for VL and the end of the same phase for CL. High CS and SDH activities were detected in both strains, as compared with other trypanosomatids, bringing more evidence for an actively functional citric-acid cycle in L. infantum. Both strains showed higher levels of CS, ICDH, and MDH and lower SDH and ME activities when more metacyclic promastigotes were present, but in VL these changes paralleled an increase in glucose consumption, whereas in CL these changes coincided with an NH3 hyperproduction. This suggests that the energy metabolism during L. infantum growth and metacyclogenesis is affected by regulated enzymes that probably respond to changes in the culture medium in the levels of glucose and amino acids.

Ammonia↗
PubMed2000

Ticlopidine, Alka-Seltzer, or a combination of citric acid with aspirin: effects on platelet aggregation in individuals with an insufficient response to aspirin alone.

Aspirin (ASA) does not effectively lower platelet aggregation in all people. The platelet aggregation (PA) score is an easily used clinical method for measuring the effect in individuals of antiplatelet medications. Fifteen apparently healthy subjects (2 men and 13 women), selected for their resistance to ASA's antiaggregation effect, completed a sequential trial of ticlopidine, Alka-Seltzer, and ASA + citric acid (CTA). Ticlopidine was the strongest aggregation inhibitor and the ASA + CTA combination was more inhibitory than Alka-Seltzer. It was determined that measuring antiaggregation effects of a particular agent in an individual prior to usage would optimize treatment. The PA score methodology provides a means for testing patients prior to antiplatelet therapy for prevention and treatment of the thrombotic complications of vascular disease.

Adult↗
PubMed2004

Use of ascorbic and citric acids to increase dialyzable iron from vinal (Prosopis ruscifolia) pulp.

Vinal (Prosopis ruscifolia) is an ecologically important wild leguminous tree that grows spontaneously in Argentine deforested lands, the fruit of which is consumed by humans and animals. Because considerable iron content with low to intermediate availability has been previously reported in vinal pulps, its enhancement would be of interest. Iron availability was determined as iron dialyzability using an in vitro technique. Response surface methodology was used to evaluate iron availability increase after adding ascorbic and/or citric acids to vinal pulp at different mM acid/mM Fe ratios. Those ratios ranged from 0.05:1 to 9.95:1 and from 0.5:1 to 99.5:1 for ascorbic acid/Fe (AA:Fe) and citric acid/Fe (CA:Fe), respectively. The obtained second- and first-order polynomial equations showed that AA:Fe and CA:Fe molar ratios linear terms had a significant effect on iron dialyzability increase (P < or = 0.05). It was possible to enhance iron availability to a maximum of 4.6 times. Additional confirmatory experiments were made adding the same organic acids to different vinal pulps and to a traditional cake prepared with vinal pulp called "patay." There were no significant differences (p > 0.05) between predicted values obtained by the model and experimental results.

Absorption↗
PubMed1992

Beta-oxidation as channeled reaction linked to citric acid cycle: evidence from measurements of mitochondrial pyruvate oxidation during fatty acid degradation.

1. The kinetics of mitochondrial mammalian pyruvate dehydrogenase multienzyme complex (PDHC) is studied by the formation of CO2 using tracer amounts of [1-14C]pyruvate. It is found that the Hill plot results in a (pseudo-)cooperativity with a transition of n-1----3 at a pyruvate concentration about Ks. 2. Addition of L-carnitine, octanoate, palmitoyl-CoA or palmitate + L-carnitine + fatty acid-binding protein results in a Hill coefficient of n = 2 following the kinetics of pyruvate oxidation. 3. Addition of fatty acid-binding protein to an assay system oxidizing palmitate in presence of L-carnitine alters the pattern of the kinetics in the Hill plot so that an apparently lower level of L-carnitine is necessary for the reaction course of beta-degradation. 4. It is concluded that beta-degradation is a coordinated, multienzyme-complex based mechanism tightly linked to citric acid cycle and it is proposed that L-carnitine is actively involved into the reaction and not only functioning as carrier-molecule for transmembrane transport.

Animals↗
PubMed1991

The effect of citric acid treatment on periodontal healing after replantation of permanent teeth.

The aim of this study was to evaluate the effect of surface demineralization on the healing of 120 replanted teeth in fifteen 8- to 16-month-old dogs. Replanted teeth were divided into two groups (A and B). In group A, teeth were replanted following planing of the entire root surface. In group B, teeth were replanted following planing and surface demineralization with citric acid. Replanted teeth were splinted for 7 days, and observation periods were 3, 14 and 56 days. A total of 95 teeth and their surrounding tissues were examined histologically under a light microscope. Histological examination of specimens 3 days after replantation revealed that initial reunion between the root and the alveolar periodontal ligament fibres was via a fibrin-like network in both groups. Fourteen days after replantation histological observations showed superior healing in group B with regard to epithelial condition, periodontal ligament fibre reattachment to the root surface, resorption and functional arrangement of the periodontal ligament fibres. By 56 days after replantation, healing was superior in group A; group B was characterized by severe inflammatory and replacement resorption. These results indicated that surface demineralization had an initial positive effect, but later led to impaired healing.

Animals↗
PubMed1995

Capsazepine inhibits cough induced by capsaicin and citric acid but not by hypertonic saline in guinea pigs.

Acidic solutions mimick many of the effects of capsaicin (Cap), including pain, bronchoconstriction, cough, and sensory neuropeptide release. Evidence from the use of the Cap antagonist capsazepine suggests that in some cases protons act at the Cap receptor. In the present study, we have investigated whether cough evoked by Cap and citric acid (CA) is mediated specifically via the Cap receptor on airway sensory nerves. We have examined the effects of capsazepine on Cap-, CA-, and hypertonic saline-induced cough and also on CA-induced nasal irritation in awake guinea pigs. Capsazepine was nebulized for 5 min before cough challenges with Cap for 5 min and CA for 10 min. Control animals were pretreated with vehicle alone. Capsazepine (100 microM) inhibited the cough response to 30 microM Cap from 0.77 +/- 0.14 coughs/min in control animals to 0.23 +/- 0.08 coughs/min (P < 0.05) and to 80 microM Cap from 1.4 +/- 0.23 to 0.3 +/- 0.11 coughs/min (P < 0.01). There was no effect, however, of lower concentrations of capsazepine (5 and 10 microM) against Cap-evoked cough. At a concentration of 100 microM, capsazepine also inhibited the coughing induced by 0.25 M CA from 1.8 +/- 0.26 to 0.93 +/- 0.31 coughs/min (P < 0.05) but not that induced by 0.5 M CA. Nasal irritation induced by 0.25 M CA, but not by 0.5 M CA, was also inhibited by capsazepine from 2.47 +/- 0.37 to 0.75 +/- 0.31 nose wipes/min (P < 0.05). This inhibitory effect of capsazepine did not appear to reflect a nonspecific suppression of the cough reflex, since cough evoked by exposure to hypertonic (7%) saline for 10 min was unaffected by pretreatment with capsazepine (100 microM). These data show that capsazepine is a specific inhibitor of Cap- and CA-induced cough in guinea pigs. Moreover, they suggest that low pH stimuli evoke cough and nasal irritation by an action at the Cap receptor, either directly or through the release of an intermediate agent.

Animals↗
PubMed1982

Progressive infantile poliodystrophy (Alpers' disease) with a defect in citric acid cycle activity in liver and fibroblasts.

We present the case history of a boy, who died at the age of 3 1/2 years after a rapidly progressive neurologic disorder, characterized by psychomotor retardation, hypotonia, hemiparesis, seizures and myoclonic contractions. Histopathologic studies showed slight lipid storage in liver. Autopsy showed the characteristic features of progressive infantile poliodystrophy (Alpers' disease); ultrastructural examination showed an increased density of mitochondria in cerebral gray matter. Biochemical studies in leukocytes, cultured fibroblasts and liver indicated a deficiency in the citric acid cycle between succinate and fumarate; this deficiency was not present in muscle tissue. This study supports the view that progressive infantile poliodystrophy is associated with abnormalities in pyruvate metabolism and/or in cell mitochondria.

Brain↗
PubMed1977

Urea biosynthesis I. The urea cycle and relationships to the citric acid cycle.

The urea cycle consist of five enzymatically controlled steps that are catalyzed by carbamyl phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinase, and arginase, respectively. The complete cycle is present in physiological meaningful levels in the liver of terrestrial vertebrates, and in man represents the sole mechanism for ammonia disposal. The formation of carbamyl phosphate and the synthesis of argininosuccinate are potential limiting steps in urea biosynthesis but substrate and not enzymes levels are rate-limiting under physiological conditions. In the adult, urea cycle enzymes change as a unit, and are largely influenced by dietary protein content. The urea cycle is closely linked to the citric acid cycle deriving one of its nitrogens through transamination of oxalacetate to form asparate and returns fumarate to that cycle. The biosynthesis of urea demands the expenditure of energy but less than 20% of the energy derived from metabolism of gluconeogenic amino acids is required for ureogenesis. Embryological development of the urea cycle in the tadpole and in mammalian fetal liver therefore permits use of amino acids as new sources of energy to meet oxidative demands for continuing growth.

Ammonia↗
PubMed1980

The clinical effects of citric acid and laterally positioned pedicle grafts in the treatment of denuded root surfaces. A pilot study.

A new technique of a combined mechanical-chemical root preparation to enhance reattachment of pedicle grafts to previously denuded root surfaces is described. The clinical results of two documented cases are presented. The findings of this pilot study indicate that the technique is well tolerated by the patients, yielding a normal postoperative healing pattern and a clinical gain in the attachment level. These preliminary results may be attributed to: (1) Total elimination of bacterial endotoxin from the root surfaces by instrumentation and topical application of saturated citric acid at pH 1.0 for 3 minutes; (2) chemical exposure of dentin collagen fibrils, into which the graft may reattach; and (3) induction of cementogenesis by the exposed dentin.

Adult↗
PubMed1973

The effect of citric acid and its sodium salts in test meals on the gastric outputs of acid and of chloride.

Five subjects were given 750 ml. test meals lasting 10-20 min, containing 0-300 mN citric acid, monosodium dihydrogen citrate, disodium monohydrogen citrate or trisodium citrate.1. Increase in concentration of sodium citrate in the range 0-125 mN gave increasing outputs of acid and chloride.2. The more acid the meal for any given citrate ion concentration, the less the output of acid and chloride.3. The greater the concentration of an acid citrate salt, the less the output of acid.4. There was evidence of loss of acid from the stomach by diffusion with the more acid meals.

Chlorides↗