The complex niche of fish gut is often characterized by the associated microorganisms that have implications in fish gut-health nexus. Although efforts to distinguish the microbial communities have highlighted their disparate structure along the gut length, remarkably little information is available about their distinct structural and functional profiles in different gut compartments in different fish species. Here, we performed comparative taxonomic and predictive functional analyses of the foregut and hindgut microbiota in an omnivorous freshwater fish species, Cyprinus carpio var. specularis, commonly known as mirror carp. Our analyses showed that the hindgut microbiota could be distinguished from foregut based on the abundance of ammonia-oxidizing, denitrifying, and nitrogen-fixing commensals of families such as Rhodospirillaceae, Oxalobacteraceae, Nitrosomonadaceae, and Nitrospiraceae. Functionally, unique metabolic pathways such as degradation of lignin, 2-nitrobenzoate, vanillin, vanillate, and toluene predicted within hindgut also hinted at the ability of hindgut microbiota for assimilation of nitrogen and detoxification of ammonia. The study highlights a major role of hindgut microbiota in assimilating nitrogen, which remains to be one of the limiting nutrients within the gut of mirror carp.

• MeSH
• amoniak * metabolismus   MeSH
• Bacteria * klasifikace   metabolismus   genetika   izolace a purifikace   MeSH
• dusík * metabolismus   MeSH
• fylogeneze MeSH
• gastrointestinální trakt mikrobiologie   metabolismus   MeSH
• kapři * mikrobiologie   metabolismus   MeSH
• metabolická inaktivace MeSH
• metabolické sítě a dráhy MeSH
• RNA ribozomální 16S genetika   MeSH
• střevní mikroflóra * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

The most common ureagenesis defect is X-linked ornithine transcarbamylase (OTC) deficiency which is a main target for novel therapeutic interventions. The spf ash mouse model carries a variant (c.386G>A, p.Arg129His) that is also found in patients. Male spf ash mice have a mild biochemical phenotype with low OTC activity (5%-10% of wild-type), resulting in elevated urinary orotic acid but no hyperammonemia. We recently established a dried blood spot method for in vivo quantification of ureagenesis by Gas chromatography-mass spectrometry (GC-MS) using stable isotopes. Here, we applied this assay to wild-type and spf ash mice to assess ureagenesis at different ages. Unexpectedly, we found an age-dependency with a higher capacity for ammonia detoxification in young mice after weaning. A parallel pattern was observed for carbamoylphosphate synthetase 1 and OTC enzyme expression and activities, which may act as pacemaker of this ammonia detoxification pathway. Moreover, high ureagenesis in younger mice was accompanied by elevated periportal expression of hepatic glutamine synthetase, another main enzyme required for ammonia detoxification. These observations led us to perform a more extensive analysis of the spf ash mouse in comparison to the wild-type, including characterization of the corresponding metabolites, enzyme activities in the liver and plasma and the gut microbiota. In conclusion, the comprehensive enzymatic and metabolic analysis of ureagenesis performed in the presented depth was only possible in animals. Our findings suggest such analyses being essential when using the mouse as a model and revealed age-dependent activity of ammonia detoxification.

• MeSH
• amoniak metabolismus   MeSH
• hyperamonemie genetika   metabolismus   patologie   MeSH
• játra metabolismus   patologie   MeSH
• lidé MeSH
• močovina metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši transgenní MeSH
• myši MeSH
• nemoc z nedostatku ornithinkarbamoyltransferázy genetika   metabolismus   patologie   MeSH
• ornithinkarbamoyltransferasa genetika   MeSH
• stárnutí fyziologie   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Histidine (HIS) is an essential amino acid investigated for therapy of various diseases, used for tissue protection in transplantation and cardiac surgery, and as a supplement to increase muscle performance. The data presented in the review show that HIS administration may increase ammonia and affect the level of several amino acids. The most common are increased levels of alanine, glutamine, and glutamate and decreased levels of glycine and branched-chain amino acids (BCAA, valine, leucine, and isoleucine). The suggested pathogenic mechanisms include increased flux of HIS through HIS degradation pathway (increases in ammonia and glutamate), increased ammonia detoxification to glutamine and exchange of the BCAA with glutamine via L-transporter system in muscles (increase in glutamine and decrease in BCAA), and tetrahydrofolate depletion (decrease in glycine). Increased alanine concentration is explained by enhanced synthesis in extrahepatic tissues and impaired transamination in the liver. Increased ammonia and glutamine and decreased BCAA levels in HIS-treated subjects indicate that HIS supplementation is inappropriate in patients with liver injury. The studies investigating the possibilities to elevate carnosine (beta-alanyl-L-histidine) content in muscles show positive effects of beta-alanine and inconsistent effects of HIS supplementation. Several studies demonstrate HIS depletion due to enhanced availability of methionine, glutamine, or beta-alanine.

• MeSH
• aminokyseliny metabolismus   MeSH
• amoniak metabolismus   MeSH
• histidin farmakologie   MeSH
• játra účinky léků   metabolismus   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• lidé MeSH
• potravní doplňky MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The rationale for recommendation of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in treatment of liver failure is based on their unique pharmacologic properties, stimulatory effect on ammonia detoxification to glutamine (GLN), and decreased concentrations in liver cirrhosis. Multiple lines of evidence have shown that the main cause of the BCAA deficiency in liver cirrhosis is their consumption in skeletal muscle for synthesis of glutamate, which acts as a substrate for ammonia detoxification to GLN and that the BCAA administration to patients with liver failure may exert a number of positive effects that may be more pronounced in patients with marked depression of BCAA levels. On the other hand, due to the stimulatory effect of BCAA on GLN synthesis, BCAA supplementation may lead to enhanced ammonia production from GLN breakdown in the intestine and the kidneys and thus exert harmful effects on the development of hepatic encephalopathy. Therefore, to enhance therapeutic effectiveness of the BCAA in patients with liver injury, their detrimental effect on ammonia production, which is negligible in healthy people and/or patients with other disorders, should be avoided. In treatment of hepatic encephalopathy, simultaneous administration of the BCAA (to correct amino acid imbalance and promote ammonia detoxification to GLN) with α-ketoglutarate (to inhibit GLN breakdown to ammonia in enterocytes) and/or phenylbutyrate (to enhance GLN excretion by the kidneys) is suggested. Attention should be given to the type of liver injury, gastrointestinal bleeding, signs of inflammation, and the dose of BCAA.

• MeSH
• amoniak metabolismus   MeSH
• fenylbutyráty metabolismus   MeSH
• glutamin metabolismus   MeSH
• jaterní cirhóza farmakoterapie   MeSH
• jaterní encefalopatie farmakoterapie   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• kyseliny ketoglutarové metabolismus   MeSH
• ledviny účinky léků   metabolismus   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• větvené aminokyseliny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Hyperammonemia and severe amino acid imbalances play central role in hepatic encephalopathy (HE). In the article is demonstrated that the main source of ammonia in cirrhotic subjects is activated breakdown of glutamine (GLN) in enterocytes and the kidneys and the main source of GLN is ammonia detoxification to GLN in the brain and skeletal muscle. Branched-chain amino acids (BCAA; valine, leucine, and isoleucine) decrease due to activated GLN synthesis in muscle. Aromatic amino acids (AAA; phenylalanine, tyrosine, and tryptophan) and methionine increase due to portosystemic shunts and reduced ability of diseased liver. The effects on aminoacidemia of the following variables that may affect the course of liver disease are discussed: nutritional status, starvation, protein intake, inflammation, acute hepatocellular damage, bleeding from varices, portosystemic shunts, hepatic cancer, and renal failure. It is concluded that (1) neither ammonia nor amino acid concentrations correlate closely with the severity of liver disease; (2) BCAA/AAA ratio could be used as a good index of liver impairment and for early detection of derangements in amino acid metabolism; (3) variables potentially leading to overt encephalopathy exert substantial but uneven effects; and (4) careful monitoring of ammonia and aminoacidemia may discover important break points in the course of liver disease and indicate appropriate therapeutic approach. Of special importance might be isoleucine deficiency in bleeding from varices, arginine deficiency in sepsis, and a marked rise of GLN and ammonia levels that may appear in all events leading to HE.

• MeSH
• aminokyseliny aromatické krev   MeSH
• amoniak krev   MeSH
• dietní proteiny aplikace a dávkování   MeSH
• glutamin krev   MeSH
• hyperamonemie krev   patologie   MeSH
• jaterní cirhóza krev   patologie   MeSH
• jaterní encefalopatie krev   patologie   MeSH
• kosterní svaly metabolismus   MeSH
• lidé MeSH
• mozek metabolismus   MeSH
• větvené aminokyseliny krev   MeSH
• zánět krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Branched-chain amino acid (BCAA; valine, leucine, and isoleucine) supplementation is common for patients with liver cirrhosis due to decreased levels of BCAA in the blood plasma of these patients, which plays a role in pathogenesis of hepatic encephalopathy and cachexia. The unique pharmacologic properties of BCAA also are a factor for use as supplementation in this population. In the present article, BCAA is shown to provide nitrogen to alpha-ketoglutarate (α-KG) for synthesis of glutamate, which is a substrate for ammonia detoxification to glutamine (GLN) in the brain and muscles. The article also demonstrates that the favorable effects of BCAA supplementation might be associated with three adverse effects: draining of α-KG from tricarboxylic acid cycle (cataplerosis), increased GLN content and altered glutamatergic neurotransmission in the brain, and activated GLN catabolism to ammonia in the gut and kidneys. Cataplerosis of α-KG can be attenuated by dimethyl-α-ketoglutarate, l-ornithine-l-aspartate, and ornithine salt of α-KG. The pros and cons of GLN elimination from the body using phenylbutyrate (phenylacetate), which may impair liver regeneration and decrease BCAA levels, should be examined. The therapeutic potential of BCAA might be enhanced also by optimizing its supplementation protocol. It is concluded that the search for strategies attenuating adverse and increasing positive effects of the BCAA is needed to include the BCAA among standard medications for patients with cirrhosis of the liver.

• MeSH
• amoniak metabolismus   MeSH
• jaterní cirhóza farmakoterapie   metabolismus   MeSH
• kyseliny ketoglutarové metabolismus   MeSH
• lidé MeSH
• potravní doplňky * MeSH
• větvené aminokyseliny škodlivé účinky   metabolismus   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Studies from the last decades indicate that increased levels of ammonia contribute to muscle wasting in critically ill patients. The aim of the article is to examine the effects of two different causes of hyperammonemia-increased ATP degradation in muscles during strenuous exercise and impaired ammonia detoxification to urea due to liver cirrhosis. During exercise, glycolysis, citric acid cycle (CAC) activity, and ATP synthesis in muscles increase. In cirrhosis, due to insulin resistance and mitochondrial dysfunction, glycolysis, CAC activity, and ATP synthesis in muscles are impaired. Both during exercise and in liver cirrhosis, there is increased ammonia detoxification to glutamine (Glu + NH3 + ATP → Gln + ADP + Pi), increased drain of ketoglutarate (α-KG) from CAC for glutamate synthesis by α-KG-linked aminotransferases, glutamate, aspartate, and α-KG deficiency, increased oxidation of branched-chain amino acids (BCAA; valine, leucine, and isoleucine), and protein-energy wasting in muscles. It is concluded that ammonia can contribute to muscle wasting regardless of the cause of its increased levels and that similar strategies can be designed to increase muscle performance in athletes and reduce muscle loss in patients with hyperammonemia. The pros and cons of glutamate, α-KG, aspartate, BCAA, and branched-chain keto acid supplementation are discussed.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Enzymes scavenging reactive oxygen species (ROS) are important for cell protection during stress and aging. A deficiency in these enzymes leads to ROS imbalance, causing various disorders in many organisms, including yeast. In contrast to liquid cultures, where fitness of the yeast population depends on its ROS scavenging capability, the present study suggests that Saccharomyces cerevisiae cells growing in colonies capable of ammonia signaling use a broader protective strategy. Instead of maintaining high levels of antioxidant enzymes for ROS detoxification, colonies activate an alternative metabolism that prevents ROS production. Colonies of the strain deficient in cytosolic superoxide dismutase Sod1p thus developed the same way as wild type colonies. They produced comparable levels of ammonia and underwent similar developmental changes (expression of genes of alternative metabolism and center margin differentiation in ROS production, cell death occurrence, and activities of stress defense enzymes) and did not accumulate stress-resistant suppressants. An absence of cytosolic catalase Ctt1p, however, brought colonies developmental problems, which were even more prominent in the absence of mitochondrial Sod2p. sod2Delta and ctt1Delta colonies failed in ammonia production and sufficient activation of the alternative metabolism and were incapable of center margin differentiation, but they did not increase ROS levels. These new data indicate that colony disorders are not accompanied by ROS burst but could be a consequence of metabolic defects, which, however, could be elicited by imbalance in ROS produced in early developmental phases. Sod2p and homeostasis of ROS may participate in regulatory events leading to ammonia signaling.

• MeSH
• amoniak metabolismus   MeSH
• biologické modely MeSH
• cytosol metabolismus   MeSH
• epigeneze genetická MeSH
• geny hub MeSH
• glutaminsynthetasa metabolismus   MeSH
• glutathionperoxidasa metabolismus   MeSH
• katalasa metabolismus   MeSH
• mitochondrie metabolismus   MeSH
• mutace MeSH
• oxidační stres MeSH
• reaktivní formy kyslíku MeSH
• Saccharomyces cerevisiae - proteiny metabolismus   MeSH
• Saccharomyces cerevisiae fyziologie   metabolismus   MeSH
• signální transdukce MeSH
• Publikační typ
• práce podpořená grantem MeSH

Some people consume chronically glutamine (GLN) in high quantities (~40 g/d), although a number of biochemical pathways and cellular functions may be negatively affected. The following side effects of GLN supplementation are discussed: (1) Alterations in amino acid transport-as GLN shares the transporters with other amino acids, enhanced GLN intake may impair amino acid distribution among tissues and their absorption in the gut and kidneys. (2) Alterations in GLN metabolism-GLN supplementation may impair synthesis of endogenous GLN and enhance glutamate and ammonia production. (3) Alterations in ammonia transport-GLN supplementation may impair ammonia detoxification and negatively affect the role of GLN as the carrier of ammonia among tissues. (4) Abnormalities in aminoacidemia-increased plasma levels of GLN, glutamate, citrulline, ornithine, arginine, and histidine and decreased levels of valine, leucine, isoleucine, glycine, threonine, serine, and proline are reported. (5) Alterations in immune system-as GLN has immunomodulating properties, the effect of chronic GLN consumption on the immune system needs to be assessed. (6) Effect on tumor growth-it should be elucidated whether chronic intake of GLN increases the risk of cancer. (7) Effect of the withdrawal of GLN supplementation-due to the adaptive response of the organism to enhanced GLN consumption, the withdrawal of GLN may enhance the risk of health problems resulting from GLN deficiency. It is concluded that enhanced intake of GLN has substantial side effects, and long-term studies should be performed to justify chronic consumption of a GLN-enriched diet.

• MeSH
• aminokyseliny krev   MeSH
• amoniak metabolismus   MeSH
• gastrointestinální trakt účinky léků   metabolismus   MeSH
• glutamin aplikace a dávkování   škodlivé účinky   biosyntéza   krev   MeSH
• imunitní systém účinky léků   metabolismus   MeSH
• játra účinky léků   metabolismus   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• ledviny účinky léků   metabolismus   MeSH
• lidé MeSH
• mozek účinky léků   metabolismus   MeSH
• potravní doplňky * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

There is substantial clinical and experimental evidence that ammonia is a major factor in the pathogenesis of hepatic encephalopathy. In the article is demonstrated that in hepatocellular dysfunction, ammonia detoxification to glutamine (GLN) in skeletal muscle, brain, and likely the lungs, is activated. In addition to ammonia detoxification, enhanced GLN production may exert beneficial effects on the immune system and gut barrier function. However, enhanced GLN synthesis may exert adverse effects in the brain (swelling of astrocytes or altered neurotransmission) and stimulate catabolism of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in skeletal muscle. Furthermore, the majority of GLN produced is released to the blood and catabolized in enterocytes and the kidneys to ammonia, which due to liver injury escapes detoxification to urea and appears in peripheral blood. As only one molecule of ammonia is detoxified in GLN synthesis whereas two molecules may appear in GLN breakdown, these events can be seen as a vicious cycle in which enhanced ammonia concentration activates synthesis of GLN leading to its subsequent catabolism and increase in ammonia levels in the blood. These alterations may explain why therapies targeted to intestinal bacteria have only a limited effect on ammonia levels in patients with liver failure and indicate the needs of new therapeutic strategies focused on GLN metabolism. It is demonstrated that each of the various treatment options targeting only one the of the ammonia-lowering mechanisms that affect GLN metabolism, such as enhancing GLN synthesis (BCAA), suppressing ammonia production from GLN breakdown (glutaminase inhibitors and alpha-ketoglutarate), and promoting GLN elimination (phenylbutyrate) exerts substantial adverse effects that can be avoided if their combination is tailored to the specific needs of each patient.

• MeSH
• amoniak metabolismus   MeSH
• enterocyty metabolismus   MeSH
• fenylbutyráty škodlivé účinky   farmakologie   terapeutické užití   MeSH
• glutamin metabolismus   MeSH
• glutaminasa antagonisté a inhibitory   MeSH
• hyperamonemie farmakoterapie   etiologie   metabolismus   MeSH
• jaterní encefalopatie dietoterapie   farmakoterapie   metabolismus   MeSH
• játra metabolismus   MeSH
• kosterní svaly metabolismus   MeSH
• kritický stav MeSH
• kyselina glutamová metabolismus   farmakologie   terapeutické užití   MeSH
• kyseliny ketoglutarové škodlivé účinky   farmakologie   terapeutické užití   MeSH
• ledviny metabolismus   MeSH
• lékové interakce MeSH
• lidé MeSH
• mikrobiota MeSH
• mozek metabolismus   MeSH
• orgánová specificita MeSH
• střeva mikrobiologie   MeSH
• větvené aminokyseliny metabolismus   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH