Is ammonia a pathogenetic factor in Alzheimer's disease?

An attempt was made to review experimental evidence in favor of the idea that ammonia plays a role in dementia of the Alzheimer type (DAT). Hyperammonemia causes biochemical and cellular dysfunctions in the brain, which can be found in brains of DAT patients. The most conspicuous among these findings are astrocytosis, impairment of glucose utilization, and a decreased rate of energy metabolism, and the impairment of neurotransmission, with a net increase in excitability and glutamate release. The derangement of lysosomal processing of proteins is another potential site of ammonia action. This aspect is especially important in view of the growing evidence for the role of the endosomal-lysosomal system in the formation of amyloidogenic fragments from -amyloid precursor protein. Ammonia is not considered a primary factor of the disease. However, since hyperammonemia and release of ammonia from the brains of DAT patients is well supported by published observations, ammonia should be taken into account as a factor that contributes to manifestations and the progression of DAT. If elevated ammonia concentrations turn out to be indeed as important in DAT, as is suggested in this review, rational therapeutic avenues can be envisaged that lead to the amelioration of symptoms and progression of the disease.Abbreviations -AP -amyloid protein - -APP -amyloid precursor protein - CNS central nervous system - DAT dementia of the Alzheimer type - GABA -aminobutyrate - MAO monoamine oxidase - NAD nicotinamide adenine dinucleotide This paper is dedicated to Rudi Vrba, a pioneer of the neurochemistry of ammonia, and a friend, at the occasion of his 68th birthday.     

Extreme isotopic depletion of nitrogen in New Zealand lithophytes and epiphytes; the result of diffusive uptake of atmospheric ammonia?

Several lichens and the terrestrial alga Trentepohlia were found to have extremely depleted ¹⁵N signatures at two sites near the Rotorua geothermal area, New Zealand. Values, typically −20‰, with several extreme cases of −24‰, are more isotopically depleted than any previously quoted δ¹⁵N signature for vegetation growing in natural environments. For Trentepohlia, distance from a geothermal source did not affect isotopic signature. A 100-km transect showed that the phenomenon is widespread and the discrimination is not related to substrate N, or to elevation. Rainfall NHx and atmospheric gaseous NH₃ (NH_3(g)) were shown to be isotopically depleted in the range −1‰ to −8‰ and could not, of themselves, be responsible for the plant values obtained. A simulation of Trentepohlia thallus was created using an acidified fiberglass mat and was allowed to absorb NH_3(g) from the atmosphere. Mats exposed at the geothermal sites and on farmland showed a significant further depletion of ¹⁵N to −17‰. We hypothesize that the extreme isotopic depletion is due to dual fractionation: firstly by the volatilization of NH_3(g) from aqueous sources into the atmosphere; secondly by the diffusive assimilation of that NH_3(g) into vegetation. We further hypothesize that lithophytes, epiphytes, and higher plants, growing on strongly N-limited substrates, will show this phenomenon more or less, depending on the proportion of diffusively assimilated NH_3(g) utilized as a N source. Many of the isotopically depleted δ¹⁵N signatures in vegetation, previously reported in the literature, especially epiphytes, may be due to this form of uptake depending on the concentration of atmospheric NH_3(g), and the degree of reliance on that form of N.     

Complete ammonia oxidation: an important control on nitrification in engineered ecosystems?

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Are Amazonian fish more sensitive to ammonia? Toxicity of ammonia to eleven native species

Little is known about the tolerance of Amazonian fish to ammonia. However, elevated ammonia of anthropogenic origin may now occur. As Amazonian fish evolved in waters which are generally acidic (i.e., low NH₃), we hypothesized that they would be more sensitive to ammonia than other freshwater fish. The acute (96-h) toxicity of NH₄Cl was tested in native ion-poor soft water (pH 7.0, ~28 °C) using semi-static tests with 11 species. Species sensitivity distributions (SSDs) for LC50_96 h and LC10_96 h and calculations of the hazardous concentrations to the most sensitive 5% (HC5 values) were tabulated. Values of LC50_96 h/LC10_96 h (in mM total ammonia) ranged from 2.24/0.78 for Paracheirodon axelrodi (most sensitive) to 19.53/16.07 for Corydoras schwartzi (most tolerant). These results confirm our hypothesis that Amazonian fish are more sensitive to ammonia than other freshwater species. High levels of ammonia may be associated with hypoxia, especially during dry periods. Simultaneous hypoxia (15–20% saturation) exacerbated ammonia toxicity in the most sensitive species (P. axelrodi), but not in Astronotus ocellatus or Corydoras schwartzi, a facultative air-breather where prevention of air access doubled ammonia toxicity. The present data are useful in generating regulatory guidelines in Amazonian waters and indicate that further studies incorporating hypoxia and air access/denial are needed.     

Cold-temperate climate: a factor for selection of ammonia oxidizers in upland soil?

Ammonia-oxidizing bacteria in various upland soils show a rather large diversity with respect to their amoA genes (coding for a subunit of the ammonium monooxygenase). It is known that the community structure of ammonia-oxidizing bacteria in upland soils is influenced by different selective factors, such as pH, gravimetric water content, fertilizer treatment, and temperature. The question, from an ecological point of view, is whether a particular ecophysiological factor, such as temperature, could select for a particular community structure of ammonia oxidizers in upland soils that would be represented by distinct clusters of the amoA gene (AmoA cluster). Studying the literature, including recent publications and our own unpublished results, we found that AmoA clusters 3a, 3b, and 9-12 apparently exhibited no preference for either subtropical/tropical soils (i.e., warm regions) or temperate cold soils. However, AmoA clusters 1 and 4 (and perhaps cluster 2) seem to occur predominantly in soils from cold-temperate regions. Here we review the evidence for a temperature effect on the global distribution of amoA genes in warm- and cold-temperate soils.     

Novel formation of α-amino acid from α-oxo acids and ammonia in an aqueous medium

In the course of a study of possible mechanisms for chemical evolution in the primeval sea, we found the novel formation of -amino acids and N-acylamino acids from -oxo acids and ammonia in an aqueous medium. Glyoxylic acid reacted with ammonia to form N-oxalylglycine, which gave glycine in a 5–39% yield after hydrolysis with 6N HCl. Pyruvic acid and ammonia reacted to give N-acetylalanine, which formed alanine in a 3–7% overall yield upon hydrolysis. The pH optima in these reactions were between pH 3 and 4. These reactions were further extended to the formation of other amino acids. Glutamic acid, phenylalanine and alanine were formed from -ketoglutaric acid, phenylpyruvic acid and oxaloacetic acid, respectively, under similar conditions. N-Succinylglutamic acid was obtained as an intermediate in glutamic acid synthesis. Phenylacetylphenyl-alanineamide was also isolated as an intermediate in phenylalanine synthesis. Alanine, rather than aspartic acid, was produced from oxaloacetic acid. These reactions provide a novel route for the prebiotic synthesis of amino acids. A mechanism for the reactions will be proposed.     

Excited-state proton-transfer reactions of 7-azaindole with water,ammonia and mixed water–ammonia: microsolvated dynamics simulation

Dynamics simulations of excited-state multiple proton transfer (ESMPT) reactions in 7-azaindole (7AI) with ammonia, mixed water–ammonia, and water molecules were investigated by quantum dynamics simulations in the first-excited state using RI-ADC(2)/SVP-SV(P) in the gas phase. 7AI(WW), 7AI(WA), 7AI(AW) and 7AI(AA) clusters (W, water and A, ammonia) show very high probability of the excited-state triple proton transfer (ESTPT) occurrence in ranges from 20% for 7AI(WA) to 60% for 7AI(AW), respectively. Furthermore, 7AI(AW) clusters with ammonia placed near N–H of 7AI has the highest probability among other isomers. In 7AI with three molecules of bridged-planar of water, ammonia and mixed water–ammonia clusters, the excited-state quadruple proton transfer reactions occur ineffectively and rearrangement of hydrogen-bonded network on solvents also takes place prior to either ESTPT or excited-state double proton transfer. The role played by mixed-solvent is revealed with replacing H₂O with NH₃ in which the ESMPT is found to be more efficient corresponding to lower barrier in the excited state. The preferential number of solvent surrounding 7AI that facilitates the proton transfer process is two for methanol and water but this preferential number for ammonia is one.

Highlights: (i) replacing H₂O with NH₃ assists ESPT corresponding to lower barrier in the excited state; (ii) the ESMPT time of 7AI with mixed water–ammonia is in the sub-picosecond timescale; (iii) the PT tends to be concerted process with at least one ammonia, but synchronous without ammonia.     

Molecular pharming — VLPs made in plants

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Dynamics in the microbial cytome — single cell analytics in natural systems

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Simultaneous decrease in ammonia and hydrogen sulfide inhibition during the thermophilic anaerobic digestion of protein-rich stillage by biogas recirculation and air supply at 60 °C

We had proposed a novel method to reduce ammonia inhibition during thermophilic anaerobic digestion via recirculation of water-washed biogas into the headspace (R1 system) or liquid phase (R2 system) of reactors. The feasibility of reducing the ratio of recirculated biogas to biogas produced (called the biogas recirculation ratio) was investigated in the present study. Thermophilic anaerobic digestion at 53 °C and 60 °C with a biogas recirculation ratio of 150 facilitated stable digestion performance and biogas production at a higher organic loading rate of 7 g/L/d in the R1 system, while the ammonia removal efficiency increased 1.23-fold when the temperature increased from 53 °C to 60 °C. At 60 °C, the biogas recirculation ratios in the R1 and R2 systems decreased to 50 and 10, and the ammonia absorption rates were 6.1 and 8.3 mmol/L/d, respectively, without decreasing the anaerobic digestion performance. The ammonia absorption rate of 8.3 mmol/L/d in the R2 system was higher than the rate of 7.8 mmol/L/d at the biogas recirculation ratio of 150 in the R1 system. The hydrogen sulfide content in the biogas was reduced to less than 50 ppm by supplying air at 3% of the amount of biogas produced into the reactor.     

Short‐term effect of hypoxia on ammonia excretion and respiration rates in the crab carcinus maenas

The metabolic response of the crab Carcinus maenas to short‐term hypoxia (60% and 35% saturated seawater) was studied at 17.5°C in fed, 3 day‐unfed and 6 day‐unfed crabs.

Ammonia excretion rate decreased under hypoxia: a 40% and 45% decrease in the normoxic rate was observed in fed crabs at 35% saturation and in 3 day‐unfed crabs at both hypoxic levels respectively. In the 6 day‐unfed crabs, the effect of hypoxia was concealed by the effect of starvation.

Oxygen consumption rate was directly related to the external O₂ tension irrespective of the crab's nutritional state. Stressed crabs behaved as a whole, as oxygen‐conformers.

A strong relationship was observed between ammonia excretion and oxygen consumption rates in fed crabs under hypoxia but not in starved crabs.     

Nitrogen-Vacancy color center in diamond — emerging nanoscale applications in bioimaging and biosensing

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IF<Subscript>1</Subscript> distribution in HepG2 cells in relation to ecto–F<Subscript>0</Subscript>F<Subscript>1</Subscript>ATPsynthase and calmodulin

F₀F₁ATPsynthase is now known to be expressed as a plasma membrane receptor for several extracellular ligands. On hepatocytes, ecto–F₀F₁ATPsynthase binds apoA–I and triggers HDL endocytosis concomitant with ATP hydrolysis. Considering that inhibitor protein IF₁ was shown to regulate the hydrolytic activity of ecto–F₀F₁ATPsynthase and to interact with calmodulin (CaM) in vitro, we investigated the subcellular distributions of IF₁, calmodulin (CaM), OSCP and β subunits of F₀F₁ATPsynthase in HepG2 cells. Using immunofluorescence and Western blotting, we found that around 50% of total cellular IF₁ is localized outside mitochondria, a relevant amount of which is associated to the plasma membrane where we also found Ca²⁺–CaM, OSCP and β. Confocal microscopy showed that IF₁ colocalized with Ca²⁺–CaM on plasma membrane but not in mitochondria, suggesting that Ca²⁺–CaM may modulate the cell surface availability of IF₁ and thus its ability to inhibit ATP hydrolysis by ecto–F₀F₁ATPsynthase. These observations support a hypothesis that the IF₁–Ca²⁺–CaM complex, forming on plasma membrane, functions in the cellular regulation of HDL endocytosis by hepatocytes.     

Somewhat in control — the role of transcription in regulating microbial metabolic fluxes

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The role of CS<Subscript>2</Subscript> in CS<Subscript>2</Subscript>/NMP mixed solvent in weakening the hydrogen bond of OH–N in coal: a DFT investigation

The interaction processes of trace amounts of N-methyl-2-pyrrolidinone (NMP), CS₂/NMP (1:1 by volume) and pure NMP solvent with the hydrogen bond of OH?N in coal were constructed and simulated by density functional theory methods. The distances and bond orders between the main related atoms, and the hydrogen bond energy of OH?N were calculated. The calculated results show that pure NMP solvent does not weaken the hydrogen bond of OH?N in coal. However, trace amounts of NMP and CS₂/NMP (1:1 by volume) have a strong capacity to weaken the hydrogen bond of OH?N in coal. The H2–N3 distances are elongated from 1.87 Å to 3.80 Å and 3.44 Å, the bond orders of H2–N3 all disappear, and the corresponding hydrogen bond energies of OH?N in coal decrease from 45.72 kJ mol^?1 to 7.06 and 11.24 kJ mol^?1, respectively. These results show that CS₂ added to pure NMP solvent plays an important role in releasing the original capacity of NMP to weaken the hydrogen bond of OH?N in coal, in agreement with experimental observations.     

Spatial variation in flux, δ<Superscript>13</Superscript>C and δ<Superscript>2</Superscript>H of methane in a small Arctic lake with fringing wetland in western Greenland

Small lakes in northern latitudes represent a significant source of CH₄ to the atmosphere that is predicted to increase with warming in the Arctic. Yet, whole-lake CH₄ budgets are lacking as are measurements of δ¹³C-CH₄ and δ²H-CH₄. In this study, we quantify spatial variability of diffusive and ebullitive fluxes of CH₄ and corresponding δ¹³C-CH₄ and δ²H-CH₄ in a small, Arctic lake system with fringing wetland in southwestern Greenland during summer. Net CH₄ flux was highly variable, ranging from an average flux of 7 mg CH₄ m^?2 d^?1 in the deep-water zone to 154 mg CH₄ m^?2 d^?1 along the lake margin. Diffusive flux accounted for ~8.5 % of mean net CH₄ flux, with plant-mediated and ebullitive flux accounting for the balance of the total net flux. Methane content of emitted ebullition was low (mean ± SD 10 ± 17 %) compared to previous studies from boreal lakes and wetlands. Isotopic composition of net CH₄ emissions varied widely throughout the system, with δ¹³C-CH₄ ranging from ?66.2 to ?55.5 ‰, and δ²H-CH₄ ranging from ?345 to ?258 ‰. Carbon isotope composition of CH₄ in ebullitive flux showed wider variation compared to net flux, ranging from ?69.2 to ?49.2 ‰. Dissolved CH₄ concentrations were highest in the sediment and decreased up the water column. Higher concentrations of CH₄ in the hypoxic deep water coincided with decreasing dissolved O₂ concentrations, while methanotrophic oxidation dominated in the epilimnion based upon decreasing concentrations and increasing values of δ¹³C-CH₄ and δ²H-CH₄. The most depleted ¹³C- and ²H-isotopic values were observed in profundal bottom waters and in subsurface profundal sediments. Based upon paired δ¹³C and δ²H observations of CH₄, acetate fermentation was likely the dominant production pathway throughout the system. However, isotopic ratios of CH₄ in deeper sediments were consistent with mixing/transition between CH₄ production pathways, indicating a higher contribution of the CO₂ reduction pathway. The large spatial variability in fluxes of CH₄ and in isotopic composition of CH₄ throughout a single lake system indicates that the underlying mechanisms controlling CH₄ cycling (production, consumption and transport) are spatially heterogeneous. Net flux along the lake margin dominated whole-lake flux, suggesting the nearshore littoral area dominates CH₄ emissions in these systems. Future studies of whole-lake CH₄ budgets should consider this significant spatial heterogeneity.