Ammonia {90000215}

Shared Reference Notes

• [1.1] [#Exercise training] 
  - Single bout of exercise > upregulated metabolic pathways of skeletal muscle substrate utilization and carbohydrate metabolites in serum > increased fecal ammonia and amino acid metabolites > increased the abundance of #Clostridia
• [1.2] 
  - Ammonia accumulates in tumors and reduces T cell function in vitro and in vivo. - Ammonia decreases T cell transsulfuration leading to altered redox status. - Clearance of ammonia reactivates T cells and decreases #Colorectal cancer.
• [1.3] [#Phenol] [#High-protein diet] 
  - Excessive fermentation of undigested protein residues in the colon increases the amount of ammonia, biogenic amines, #Indole compounds, and phenols.
• [1.4] [#Atherosclerosis] [#Streptococcus] 
  - issimilatory #Nitrate reduction > CACS-associated species > converts #Nitrate to ammonia, and having an increased activity of this pathway in the colon could potentially inhibit the potential positive cardiovascular effects of #Nitrate.
• [1.5] [#Covid-19] 
  - (1) supplementation of #Taurine (reducing musculoskeletal disorders); - (2) supplementation of #Citrulline (enhancing ammonia clearance and reducing blood #Lactate, as well as increasing #Arginine bioavailability for adequate NO production); - (3) supplementation of #Glutamine (primary source for #Neurotransmitters and immune function balancing); - (4) supplementation of antioxidants such as N-acetylcysteine or NAD + (redox balance); - (5) supplementation of #Arginine (targeting endothelial dysfunction in Long-COVID)
• [1.6] 
  - #lactulose exerts its beneficial effects on #Hepatic encephalopathy through different pathways. - First, the product of #lactulose fermentation is #Lactic acid, which is able to reduce the colonic lumen pH by releasing H+. - The ammonia in the gut reacts with proton and produces ammonium. This conversion develops a concentration gradient that increases the amount of ammonia reuptake from the blood into the gastrointestinal tract. - Second, in the presence of #lactulose in the gastrointestinal tract, the bacteria utilize the energy of #lactulose fermentation instead of the conversion of amino acids to ammonia energy. - Third, #lactulose can inhibit glutaminase and prevent the production of ammonia from #Glutamine. - Finally, #lactulose shortens the colonic transit time. Thus, it can reduce the level of ammonia in the gastrointestinal tract.
• [1.7] [#4-ethylphenol, #4-ethylphenylsulfate] 
  - A subset of the required enzymes (e.g., hydroxycinnamate reductase enzymes (HCRs), #Tyrosine ammonia-lyase (TALs)) are encoded within the genomes of many microbes (e.g., #Clostridium aerotolerans, #Clostridium xylanolyticum and #Bacteroides ovatus) > increase 4EP
• [1.8] 
  - reduction of membrane localization of tight junction protein (#ZO-1, ZO-2, #Occludin, #Claudin-1, and -3) and increased permeability in colonocytes were induced by the ammonia treatment > mitochondrial dysfunction > increase of #Oxidative stress, > intestinal barrier dysfunction.
• [#Tauro-cholic acid] - ammonia treatment on Caco-2 cells induced #Oxidative stress and mitochondrial dysfunction (e.g., reduced mitochondrial gene expression, reduction of TCA cycle intermediates, reduced mitochondrial membrane potential)
• [1.9] 
  - Ammonia has been long recognized as a metabolic waste product with well-known neurotoxic effects.
• - gut ammonia links microbe nitrogen metabolism to host stress vulnerability by maintaining brain #Glutamine availability in male mice. - abnormally low blood ammonia levels limit the brain’s availability of #Glutamine, a key metabolite produced by astrocytes that is required for presynaptic γ-aminobutyric acid (#GABA) replenishment and confers stress vulnerability through cortical GABAergic dysfunction.
• - #Chronic stress decreases blood ammonia levels by altering gut urease-positive microbiota.
• [#GABA] - ammonium chloride (NH4Cl), a commonly used expectorant in the clinic, can rescue behavioural abnormalities and GABAergic deficits in mouse models of #Depression
• - A representative urease-producing strain, #Streptococcus thermophilus, can reverse #Depression-like behaviours induced by gut microbiota that was altered by stress, whereas pharmacological inhibition of gut ammonia production increases stress vulnerability.

References Notes