Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AMMONIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed2002

Ammonia induces MK-801-sensitive nitration and phosphorylation of protein tyrosine residues in rat astrocytes.

Astrocytes play a key role in the pathogenesis of ammonia-induced neurotoxicity and hepatic encephalopathy. As shown here, ammonia induces protein tyrosine nitration in cultured rat astrocytes, which is sensitive to the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. A similar pattern of nitrated proteins is produced by NMDA. Ammonia-induced tyrosine nitration depends on a rise in [Ca2+]i, IkB degradation, and NO synthase (iNOS) induction, which are prevented by MK-801 and the intracellular Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM). Moreover, the increase in tyrosine nitration is blunted by L-NMMA, 1400W, uric acid, Cu, Zn-superoxide dismutase/catalase treatment, and methionine-sulfoximine, which indicate the involvement of reactive nitrogen intermediates and intracellular glutamine accumulation. Such reactive nitrogen intermediates additionally mediate ammonia-induced phosphorylation of the MAP-kinases Erk-1/Erk-2 and p38MAPK. Among the proteins, which are tyrosine -nitrated by ammonia, glyceraldehyde-3-phosphate dehydrogenase, the peripheral-type benzodiazepine receptor, Erk-1, and glutamine synthetase are identified. Ammonia-induced nitration of glutamine synthetase is associated with a loss of enzymatic activity. Astroglial protein tyrosine nitration is found in brains from rats after acute ammonia-intoxication or after portacaval anastomosis, indicating the in vivo relevance of the present findings. The production of reactive nitrogen intermediates and protein tyrosine nitration may alter astrocyte function and contribute to ammonia neurotoxicity.

Ammonia↗
PubMed1993

Enhanced endogenous ornithine concentrations protect against tonic seizures and coma in acute ammonia intoxication.

Pretreatment of mice with 5-fluoromethylornithine (5FMOrn), a selective inactivator of ornithine aminotransferase, diminishes the accumulation of ammonia in the brain after administration of ammonium acetate, and antagonizes ammonia-induced fatal tonic extensor convulsions. In about 50% of the treated animals the loss of the righting reflex and coma is prevented. Presumably these effects are based on the enhancement of urea formation by the increased liver ornithine concentrations. However, since brain ornithine concentrations are greatly enhanced by 5FMOrn, it is not excluded that ornithine has direct effects on cellular events involved in ammonia-induced seizure generation, even though 5FMOrn had no anticonvulsant properties in a series of established animal seizure models, including N-methyl-D,L-aspartate-induced convulsions. NMDA receptor antagonists are capable of preventing death, but do not protect against the generation of coma and tonic extensor convulsions in ammonium acetate intoxicated mice. Since no evidence was found for ammonia-induced glutamate release from rat hippocampus, there is no convincing evidence for the idea that the tonic convulsions are mediated by NMDA receptors. L-Methionine-D, L-sulfoximine (MSO)-induced seizures can be partially antagonized by pretreatment with 5FMOrn. However, the effect is considerably smaller than against ammonia-induced convulsions, although at the time of seizure onset brain ammonia levels of MSO-intoxicated mice were lower than in the animals receiving ammonium acetate. This suggests that MSO-convulsions are not entirely due to the elevation of brain ammonia concentrations, even though MSO administration mimics effects of ammonia on cortical inhibitory neuronal interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Mercaptopropionic Acid↗
PubMed1989

Ammonia assimilation pathways in nitrogen-fixing Clostridium kluyverii and Clostridium butyricum.

Pathways of ammonia assimilation into glutamic acid were investigated in ammonia-grown and N2-fixing Clostridium kluyverii and Clostridium butyricum by measuring the specific activities of glutamate dehydrogenase, glutamine synthetase, and glutamate synthase. C. kluyverii had NADPH-glutamate dehydrogenase with a Km of 12.0 mM for NH4+. The glutamate dehydrogenase pathway played an important role in ammonia assimilation in ammonia-grown cells but was found to play a minor role relative to that of the glutamine synthetase/NADPH-glutamate synthase pathway in nitrogen-fixing cells when the intracellular NH4+ concentration and the low affinity of the enzyme for NH4+ were taken into account. In C. butyricum grown on glucose-salt medium with ammonia or N2 as the nitrogen source, glutamate dehydrogenase activity was undetectable, and the glutamine synthetase/NADH-glutamate synthase pathway was the predominant pathway of ammonia assimilation. Under these growth conditions, C. butyricum also lacked the activity of glucose-6-phosphate dehydrogenase, which catalyzes the regeneration of NADPH from NADP+. However, high activities of glucose-6-phosphate dehydrogenase as well as of NADPH-glutamate dehydrogenase with a Km of 2.8 mM for NH4+ were present in C. butyricum after growth on complex nitrogen and carbon sources. The ammonia-assimilating pathway of N2-fixing C. butyricum, which differs from that of the previously studied Bacillus polymyxa and Bacillus macerans, is discussed in relation to possible effects of the availability of ATP and of NADPH on ammonia-assimilating pathways.

Ammonia↗
PubMed1992

Interaction between ribulose 1,5-bisphosphate carboxylase/oxygenase activity and the ammonia assimilatory system of Rhodobacter sphaeroides.

The levels of form I and form II ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) from Rhodobacter sphaeroides were found to depend on the concentration of ammonia supplied to photolithoautotrophically grown cultures. Under conditions in which the cells rapidly depleted the available ammonia, the level of in situ RubisCO activity decreased to less than 5% maximum activity; even at its maximum level under these conditions, the RubisCO activity was only 5% of the activity obtained from cultures supplied with saturating levels of ammonia. When cells were incubated with somewhat higher but not saturating amounts of ammonia, in situ RubisCO activity decreased immediately after the cells depleted the cultures of ammonia. The decrease in activity was not due to any detectable degradation of RubisCO protein, indicative of some mechanism to regulate the activity of the enzyme in response to the intracellular levels of assimilated ammonia. Furthermore, under conditions optimum for RubisCO inactivation, in situ RubisCO activity in permeabilized whole cells greatly exceeded the levels of enzymatic activity determined in vitro in cell extracts. Blockage of ammonia assimilation by inhibition of glutamine synthetase with methionine sulfoximine prevented the recovery of form I RubisCO from pyruvate-mediated inactivation, suggesting the presence of regulatory mechanisms common to both CO2 fixation and ammonia assimilation.

Ammonia↗
PubMed1964

THE METABOLISM OF THE VOLATILE AMINES: VII. THE CLINICAL SIGNIFICANCE OF TWO COMPONENTS OF THE BLOOD AMMONIA LEVEL.

BLOOD AMMONIA LEVELS CONSIST OF TWO COMPONENTS: ammonia present in blood at the time of shedding, termed "free" ammonia, and ammonia produced by the deamidating action of the alkali reagents. Blood of healthy people contained little or no "free" ammonia while blood of patients with chronic liver disease occasionally showed levels up to 1.2 mug./ml. Patients with hepatic encephalopathy had significantly elevated levels which usually fell to zero following therapy. Levels of "free" ammonia above 0.6 mug./ml. were diagnostic of hepatic encephalopathy in patients suffering from unexplained neurological disorders.The rate of formation of ammonia by the alkali reagents was increased in patients with hepatic necrosis and was depressed in those with chronic hepatitis. The ammonia appeared to arise from the deamidation of glutamine and asparagine, present in blood in both the free and peptide forms.

Amines↗
PubMed1998

Ammonia inhibits neural cell adhesion molecule polysialylation in Chinese hamster ovary and small cell lung cancer cells.

Ammonia is a major concern in biotechnology because it often limits recombinant protein production by animal cells. Conditions, such as ammonia accumulation, in large-scale production systems can parallel those that develop within fast-growing solid tumors such as small cell lung cancer (SCLC). Ammonia's specific inhibition of the sialylation of secreted glycoproteins is well documented, but it is not known how ammonia affects membrane-bound proteins, nor what role it may have on important glycosylation determinants in cancer. We therefore examined the effects of NH4Cl on polysialic acid (PolySia) in the neural cell adhesion molecule (NCAM). By using flow cytometry combined with two NCAM antibodies, one specific for the peptide backbone and another that recognizes PolySia chains, we show that ammonia causes rapid, dose-dependent, and reversible inhibition of NCAM polysialylation in Chinese hamster ovary (CHO) and SCLC NCI-N417 cells. The decrease in PolySia was accompanied by a small increase in NCAM, suggesting that the changes were specific to the oligosaccharide. Inhibition by ammonia was greater for CHO cells, with PolySia cell surface content decreasing to 10% of control after a 4-day culture with 10 mM NH4Cl, while N417 cell PolySia was reduced by only 35%. Ammonia caused a 60% decrease in the CHO cell yield from glucose, while N417 cells were barely affected, suggesting that increased resistance to ammonia by N41 7 cells is a global rather than glycosylation-specific phenomenon. The data presented show that the tumor microenvironment may be an important factor in the regulation of PolySia expression.

Ammonia↗
PubMed1990

New roles of carnitine metabolism in ammonia cytotoxicity.

High levels of ammonia in blood and brain due to metabolic disorders are associated with neurological abnormalities. Although the mechanism of ammonia toxicity at the CNS level is still unknown, alterations in brain energy metabolism, in neurotransmitter function and direct effects on nervous impulse have been proposed. In most hyperammonemic conditions morphological changes in the liver and brain have been demonstrated, especially in mitochondria, endoplasmic reticulum and lysosomes, together with an accumulation of intracellular lipids. The treatment of hyperammonemias is uncertain and mostly directed to reduce the level of circulating ammonia; there is no current therapy aimed to counteract the molecular effects of ammonia. Administration of carnitine prevents acute ammonia toxicity and enhances the efficacy of ammonia elimination as urea and glutamine. In addition the cytotoxic effects of ammonia, possibly arising from lipid peroxidation, are ameliorated by carnitine. These data indicate the feasibility of utilization of carnitine in the therapy of human hyperammonemic syndromes, both for reducing the levels of ammonia and preventing its toxic effects.

Ammonia↗
PubMed1990

Peak blood ammonia and lactate after submaximal, maximal and supramaximal exercise in sprinters and long-distance runners.

The purpose of this study was to elucidate the difference in peak blood ammonia concentration between sprinters and long-distance runners in submaximal, maximal and supramaximal exercise. Five sprinters and six long-distance runners performed cycle ergometer exercise at 50% maximal, 75% maximal, maximal and supramaximal heart rates. Blood ammonia and lactate were measured at 2.5, 5, 7.5, 10 and 12.5 min after each exercise. Peak blood ammonia concentration at an exercise intensity producing 50% maximal heart rate was found to be significantly higher compared to the basal level in sprinters (P less than 0.01) and in long-distance runners (P less than 0.01). The peak blood ammonia concentration of sprinters was greater in supra-maximal exercise than in maximal exercise (P less than 0.05), while there was no significant difference in long-distance runners. The peak blood ammonia content after supramaximal exercise was higher in sprinters compared with long-distance runners (P less than 0.01). There was a significant relationship between peak blood ammonia and lactate after exercise in sprinters and in long-distance runners. These results suggest that peak blood ammonia concentration after supramaximal exercise may be increased by the recruitment of fast-twitch muscle fibres and/or by anaerobic training, and that the processes of blood ammonia and lactate production during exercise may be strongly linked in sprinters and long-distance runners.

Adolescent↗
PubMed1993

Astrocytes and the entry of circulating ammonia into the brain: effect of fluoroacetate.

Chronic hyperammonemia is known to lead to pathological forms of astrocytes. To test the influence of these changes on the neurotoxicity of ammonia, the glial metabolic poison fluoroacetate (FA) was applied locally, through microdialysis to the hippocampal dentate gyrus. The penetration of ammonia into the brain following the i.p. injection of 7.8 mmol/kg NH4 acetate was evaluated by measuring the ammonia and glutamine content of the microdialysate. Field EPSPs (fEPSPs) evoked by perforant path stimulation were recorded 1.5 mm from the microdialysis probe. When 20 mM FA was perfused, NH4 acetate injection increased the ammonia efflux by 300% and decreased fEPSPs by 40%, but glutamine concentration remained low. With no FA in the microdialysate, NH4 acetate treatment increased the efflux of ammonia by only 60%, did not affect fEPSPs but doubled glutamine efflux. Arterial ammonia content, as measured by microdialysis in the common carotid, increased 4-5 fold following i.p. administration of NH4 acetate, while arterial glutamine was not elevated. Systemically administered FA did not affect either of these changes significantly, but slightly reduced arterial pH. These observations indicate that FA applied by microdialysis acted locally on astrocytes and therefore impaired astrocytic function contributes to the development of hepatic encephalopathy by facilitating the entry of ammonia into the brain. Inhibition of excitatory synaptic transmission by elevated brain ammonia may underlay CNS depression in hepatic encephalopathy.

Ammonia↗
PubMed1996

Effects of ammonia on L-glutamate uptake in cultured astrocytes.

The effect of ammonia on L-glutamate (L-GLU) uptake was examined in cultured astrocytes. Acute ammonia treatment (5-10 mM) enhanced L-[3H]GLU uptake by 20-42% by increasing the Vmax; this persisted for 2 days and than started to decline. Ammonia, however, did not affect the uptake of D-[3H]aspartate (D-ASP), a non-metabolizable analog of L-GLU, that uses the same transport carrier as L-GLU. Also, L-GLU uptake was not affected during the first 2 min of the assay. Thus, ammonia did not have an acute effect of L-GLU transport (translocation); rather, ammonia enhanced the accumulation or "trapping" of L-GLU or its by-products. Chronic ammonia treatment, on the other hand, inhibited L-GLU transport in astrocytes by approximately 30-45% and this was due to a decrease in Vmax, suggesting that the number of L-GLU transporters was decreased. This inhibitory effect was observed after 1 day of treatment and persisted for at least 7 days. The inhibition of L-GLU transport was partially reversible following removal of ammonia. The effects of ammonia on L-GLU transport and uptake may explain the abnormal L-GLU neurotransmission observed in hyperammonemia/hepatic encephalopathy, and the brain swelling associated with fulminant hepatic failure.

Ammonia↗
PubMed2001

Ammonia differentially suppresses the cAMP chemotaxis of anterior-like cells and prestalk cells in Dictyostelium discoideum.

A drop assay for chemotaxis to cAMP confirms that both anterior-like cells (ALC) and prestalk cells (pst cells) respond to cAMP gradients. We present evidence that the chemotactic response of both ALC and pst cells is suppressed by ammonia, but a higher concentration of ammonia is required to suppress the response in pst cells. ALC show a chemotactic response to cAMP when moving on a substratum of prespore cells in isolated slug posteriors incubated under oxygen. ALC chemotaxis on a prespore cell substratum is suppressed by the same concentration of ammonia that suppresses ALC chemotaxis on the agar substratum in drop assays. Chemotaxis suppression is mediated by the unprotonated (NH3) species of ammonia. The observed suppression, by ammonia, of ALC chemotaxis to cAMP supports our earlier hypothesis that ammonia is the tip-produced suppressor of such chemotaxis. We discuss implications of ammonia sensitivity of pst cells and ALC with regard to the movement and localization of ALC and pst cells in the slug and to the roles played by ALC in fruiting body formation. In addition, we suggest that a progressive decrease in sensitivity to ammonia is an important part of the maturation of ALC into pst cells.

Ammonia↗
PubMed2004

Diel variation in ammonia excretion, glutamine levels, and hydration status in two species of terrestrial isopods.

Terrestrial isopods (suborder Oniscidea) excrete most nitrogen diurnally as volatile ammonia, and ammonia-loaded animals accumulate nonessential amino acids, which may constitute the major nocturnal nitrogen pool. This study explored the relationship between ammonia excretion, glutamine storage/mobilization, and water balance, in two sympatric species Ligidium lapetum (section Diplocheta), a hygric species; and Armadillidium vulgare (Section Crinocheta), a xeric species capable of water-vapor absorption (WVA). Ammonia excretion (12-h), tissue glutamine levels, and water contents were measured following field collection of animals at dusk and dawn. In both species, diurnal ammonia excretion exceeded nocturnal excretion four- to fivefold while glutamine levels increased four- to sevenfold during the night. Most glutamine was accumulated in the somatic tissues ("body wall"). While data support the role of glutamine in nocturnal nitrogen storage, potential nitrogen mobilization from glutamine breakdown (162 micromol g(-1) in A. vulgare) exceeds measured ammonia excretion (2.5 micromol g(-1)) over 60-fold. This may serve to generate the high hemolymph ammonia concentrations (and high P(NH3)) seen during volatilization. The energetic cost of ammonia volatilization is discussed in the light of these findings. Mean water contents were similar at dusk and dawn in both species, indicating that diel cycles of water depletion and replenishment were not occurring.

Adaptation, Physiological↗
PubMed1990

Ammonia as a potential mediator of adult human periodontal infection: inhibition of neutrophil function.

Neutrophils (polymorphonuclear leucocytes) are the principal cell of the host defence system. Consequently, if periodontal pathogen-derived substances in the gingival crevice significantly inhibit their function, they could shift the bacterial-host balance in favour of the bacteria. The hypothesis that ammonia can inhibit neutrophil function was tested. Ammonia was specifically selected because periodontal pathogens produce substantial amounts of ammonia. The findings indicated that ammonia can inhibit neutrophil phagocytosis, degranulation and oxygen metabolism. Ammonia decreased the total number of phagocytosing polymorphonuclear neutrophils (66% of control) and also decreased degranulation (61% of control). Ammonia decreased oxygen metabolism of both resting and stimulated neutrophils (33 and 42% of control, respectively). These observations support the hypothesis that ammonia can inhibit the function of polymorphonuclear leukocytes. They suggest that the presence of ammonia in the gingival crevice may increase the risk of development of periodontal disease.

Adult↗
PubMed1993

The concentrations of glutamine and ammonia in commercially available cell culture media.

The amino acid glutamine is an essential nutrient for cells in culture. In aqueous solutions such as liquid culture media, glutamine spontaneously decomposes into ammonia. In this study, we examined the toxicity of ammonia for two different cell lines. In mouse hybridoma cell cultures, viable cell counts were reduced at exogenous ammonia concentrations of 1000 microM. In the human promyelocytic cell line however, viable cell counts were shown to be reduced at exogenous ammonia concentrations of 300 microM. Next, we determined ammonia and glutamine levels in 11 commercially available media on the day of delivery. It was found that all media contained significantly less glutamine than prescribed. Ammonia was found in all media with concentrations ranging up to 1000 microM. Storage at both 4 degrees C and 20 degrees C caused a further degradation of glutamine and significant accumulation of ammonia in all media. The degradation curves of the various media were used to calculate the first order degradation constant k, which can be used to determine the kinetics of the spontaneous decomposition in culture media. These results suggest that precautions must be taken to avoid the deterioration of commercially available culture media, because of the decay of glutamine. Long storage times lead to a rapid decay of glutamine and an accumulation of the toxic degradation product ammonia.

Ammonia↗
PubMed1991

Polyamine-dependent production of lymphocytotoxic levels of ammonia by human peripheral blood monocytes.

The activity of polyamine oxidase down-regulates IL-2 production in cultures of peripheral blood mononuclear cells. Monocytes are the main source of this enzymatic activity which generates ammonia. We therefore assessed the production of ammonia by human monocytes. We report that human peripheral blood monocytes produce and secrete ammonia and that this activity peaks after 2 days of incubation in vitro. Ammonia production can be suppressed by inhibiting polyamine biosynthesis and polyamine oxidation; thus, the activity of polyamine oxidase in human monocytes generates ammonia. Ammonia production could serve as a measure of polyamine oxidase activity in human monocytes. The levels of ammonia produced in our system reduce human lymphocyte viability. Therefore, ammonia can be added to the list of macrophage products having cytotoxic and immunosuppressive potential.

Adult↗
PubMed2005

A new enzymatic cycling method for ammonia assay using NAD synthetase.

BACKGROUND: Ammonia is an important marker for liver diseases such as hepatitis and hepatic cirrhosis. Several methods have been developed for ammonia analysis. In particular, the enzymatic assay using glutamate dehydrogenase has been widely used. However, this method is not necessarily high in sensitivity and accuracy due to inhibition by interferences in plasma and instability over long-term storage. METHODS: We developed an ammonia assay using a system consisting of three enzymes, NAD synthetase (NADS; EC 6.3.1.5), glucose dehydrogenase (GlcDH; EC 1.1.1.47), and diaphorase (DI; EC 1.6.99.2). RESULTS: The calibration curve for ammonia with the cycling method was linear (r=0.999) up to 300 micromol/l. The within-run CVs of 10 and 20 micromol/l NH4Cl solutions and 24.1 micromol/l ammonia in human plasma were 2.3%, 1.5%, and 2.8%, respectively. The between-run CVs of them were 4.5%, 3.1%, and 2.8%, respectively. The recovery was between 96.3% and 105%, and the limit of detection was 2.4 micromol/l. No significant interference was observed with addition of the following components: hemoglobin, bilirubin, chyle, EDTA, heparin, and sodium citrate. Due to the high degree of specificity of NAD synthetase to ammonia, no amino compounds exhibited any effect on the ammonia assay. A high correlation was obtained between results of the present method (y) and a conventional glutamate dehydrogenase method in regression analysis; y=0.944x-6.160 with r=0.993 (n=125). However, an addition error was observed from Bland-Altman analysis (the 95% limits of agreement between the two methods; 9.51+/-5.92 micromol/l). CONCLUSION: This new enzymatic method is more sensitive, precise, and accurate than the conventional method. In particular, accurate assay for ammonia can be performed without interference in the presence of various compounds.

Amide Synthases↗
PubMed2006

Impacts of pH and ammonia on the leaching of Cu(II) and Cd(II) from coal fly ash.

Many coal-fired power plants are implementing ammonia-based technologies to reduce NO(x) emissions. Excess ammonia in the flue gas often deposits on the coal fly ash. Ammonia can form complexes with many heavy metals and change the leaching characteristics of these metals. This research tends to develop a fundamental understanding of the ammonia impact on the leaching of some heavy metals, exemplified by Cu(II) and Cd(II), under different pH conditions. Batch results indicated that the adsorption is the main mechanism controlling Cu(II) and Cd(II) leaching, and high concentrations of ammonia (>5,000 mg/l) can increase the release of Cu(II) and Cd(II) in the alkaline pH range. Based on the chemical reactions among fly ash, ammonia, and heavy metal ion, a mathematical model was developed to quantify effects of pH and ammonia on metal adsorption. The adsorption constants (logK) of Cu(2+), Cu(OH)(+), Cu(OH)(2), and Cu(NH(3))(m)(2+) for the fly ash under investigation were respectively 6.0, 7.7, 9.6, and 2.9. For Cd(II), these constants were respectively 4.3, 6.9, 8.8, and 2.6. Metal speciation calculations indicated that the formation of less adsorbable metal-ammonia complexes decreased metal adsorption, therefore enhanced metal leaching.

Adsorption↗
PubMed2006

Ammonia removal from pretreated methane fermentation effluent through a soil trench system: a column experiment.

In order to find the optimal running conditions and mechanisms of ammonia removal through a soil trench system that is designed for treating pretreated methane fermentation effluent, a soil column whose structure was similar to the soil trench system was prepared, and irrigated with wastewater below 30 degrees C. At the beginning, ammonia was mainly adsorbed by the soils, and the ammonia adsorption capacity of soils gradually saturated. After the 12th day, nitrification began in the soil column; the ammonia in the soil column decreased sharply, and the nitrite and nitrate peak appeared sequentially as the wastewater application rate decreased from 0.74 to 0.37 l h(-1). When the nitrification in the soil column reached a steady-state, 98% of all the ammonia in the influent was transformed into nitrate. By changing the running conditions such as temperature, aeration, and wastewater application rate, it was found that the ammonia removal efficiency can be improved by aeration and impeded by low temperature. In these three variables, wastewater application rate has much greater affect on the ammonia removal efficiency; a lower wastewater application rate can increase the ammonia removal efficiency substantially because of the longer travel time.

Adsorption↗