Paracytophagy is the cellular process whereby a cell engulfs a protrusion which extends from a neighboring cell. This protrusion may contain material, transferred between the cells; the process of paracytophagy was first described as a crucial step during cell-to-cell spread of the intracellular bacterial pathogen Listeria monocytogenes, is commonly observed in Shigella flexneri. Paracytophagy allows these intracellular pathogens to spread directly from cell to cell, thus escaping immune detection and destruction. Studies of this process have contributed to our understanding of the role of the actin cytoskeleton in eukaryotic cells. Actin is one of the main cytoskeletal proteins in eukaryotic cells; the polymerization of actin filaments is responsible for the formation of pseudopods and lamellipodia during cell motility. Cells build actin microfilaments that push the cell membrane towards the direction of advance. Nucleation factors are enhancers of actin polymerization and contribute to the formation of the trimeric polymerization nucleus.
This is a structure required to initiate the process of actin filament polymerization in a stable and efficient way. Nucleation factors such as WASP help to form the seven-protein Arp2/3 nucleation complex, which resembles two actin monomers and therefore allows for easier formation of the polymerization nucleus. Arp2/3 is able to cap the trailing end of the actin filament, allowing for faster polymerization at the "plus" end, it can bind to the side of existing filaments to promote filament branching. Certain intracellular pathogens such as the bacterial species Listeria monocytogenes and Shigella flexneri can manipulate host cell actin polymerization to move through the cytosol and spread to neighboring cells. Studies of these bacteria of Listeria Actin assembly-inducing protein, have resulted in further understanding of the actions of WASP. ActA is a nucleation promoting factor that mimics WASP, it is expressed polarized to the posterior end of the bacterium, allowing Arp2/3-mediated actin nucleation.
This pushes the bacterium in the anterior direction. In the case of Shigella, which moves using an actin comet tail, the bacterial factor recruits host cell WASPs in order to promote actin nucleation. Cells can exchange material through various mechanisms, such as by secreting proteins, releasing exosomes, or more directly engulfing pieces of adjacent cells. In one example, filopodia-like protrusions, or tunneling nanotubes directed toward neighboring cells in a culture of rat PC12 cells have been shown to facilitate transport of organelles through transient membrane fusion. In another example, during bone marrow homing, cells of the surrounding bone engulf pieces of bone marrow hematopoietic cells; these osteoblasts make contact with hematopoietic stem-progenitor cells through membrane nanotubes, pieces of the donor cells are transferred over time to various endocytic compartments of the target osteoblasts. A distinct process known as trogocytosis, the exchange of lipid rafts or membrane patches between immune cells, can facilitate response to foreign stimuli.
Moreover, exosomes have been shown to deliver not only antigens for cross-presentation, but MHCII and co-stimulatory molecules for lymphocyte T activation. In non-immune cells, it has been demonstrated that mitochondria can be exchanged intercellularly to rescue metabolically non-viable cells lacking mitochondria. Mitochondrial transfer has been observed in cancer cells. Argosomes are derived from basolateral epithelial membranes and allow communication between adjacent cells, they were first described in Drosophila melanogaster, where they act as a vehicle for the spread of molecules through the epithelia of imaginal discs. Melanosomes are transferred by filopodia from melanocytes to keratinocytes; this transfer involves a classic filopodial forming pathway, with WASP as key factors. Argosomes and other examples of epithelial transfer have been compared with the process of paracytophagy, all of which can be viewed as special cases of intercellular material transfer between epithelial cells; the two main examples of paracytophagy are the modes of cell-cell transmission of Listeria monocytogenes and Shigella flexneri.
In the case of Listeria, the process was first described in detail using electron microscopy and video microscopy. The following is a description of the process of cell-cell transmission of Listeria monocytogenes based on Robbins et al.: In an infected "donor" cell, the Listeria bacterium expresses ActA, which results in formation of the actin comet tail and movement of the bacterium throughout the cytoplasm. When the bacterium encounters the donor cell membrane, it will either ricochet off it or adhere to it and begin to push outwards, distending the membrane and forming a protrusion of 3-18 μm; the close interaction between the bacterium and the host cell membrane is thought to depend on Ezrin, a member of the ERM family of membrane-associated proteins. Ezrin attaches the actin-propelled bacterium to the plasma membrane by crosslinking the actin comet tail to the membrane, maintains this interaction throughout the protrusion process; as the normal site of infection is the gut columnar epithelium, cells are packed together and a cell protrusion from one cell will push into a neighboring "target" cell without rupturing the target cell membrane or the donor protrusion membrane.
At this point, the bacterium at the tip of the protrusion will begin to undergo "fitful movement" caused by continuing polymerizatio
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the gram-staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall sandwiched between an inner cytoplasmic cell membrane and a bacterial outer membrane. Gram-negative bacteria are found everywhere, in all environments on Earth that support life; the gram-negative bacteria include the model organism Escherichia coli, as well as many pathogenic bacteria, such as Pseudomonas aeruginosa, Neisseria gonorrhoeae, Chlamydia trachomatis, Yersinia pestis. They are an important medical challenge, as their outer membrane protects them from many antibiotics. Additionally, the outer leaflet of this membrane comprises a complex lipopolysaccharide whose lipid A component can cause a toxic reaction when these bacteria are lysed by immune cells; this toxic reaction can include fever, an increased respiratory rate, low blood pressure — a life-threatening condition known as septic shock.
Several classes of antibiotics have been designed to target gram-negative bacteria, including aminopenicillins, ureidopenicillins, beta-lactam-betalactamase combinations, Folate antagonists and carbapenems. Many of these antibiotics cover gram positive organisms; the drugs that target gram negative organisms include aminoglycosides and Ciprofloxacin. Gram-negative bacteria display these characteristics: An inner cell membrane is present A thin peptidoglycan layer is present Has outer membrane containing lipopolysaccharides in its outer leaflet and phospholipids in the inner leaflet Porins exist in the outer membrane, which act like pores for particular molecules Between the outer membrane and the cytoplasmic membrane there is a space filled with a concentrated gel-like substance called periplasm The S-layer is directly attached to the outer membrane rather than to the peptidoglycan If present, flagella have four supporting rings instead of two Teichoic acids or lipoteichoic acids are absent Lipoproteins are attached to the polysaccharide backbone Some contain Braun's lipoprotein, which serves as a link between the outer membrane and the peptidoglycan chain by a covalent bond Most, with few exceptions, do not form spores Along with cell shape, gram-staining is a rapid diagnostic tool and once was used to group species at the subdivision of Bacteria.
The kingdom Monera was divided into four divisions based on gram-staining: Firmacutes, Gracillicutes and Mendocutes. Since 1987, the monophyly of the gram-negative bacteria has been disproven with molecular studies; however some authors, such as Cavalier-Smith still treat them as a monophyletic taxon and refer to the group as a subkingdom "Negibacteria". Bacteria are traditionally classified based on their gram-staining response into the gram-positive and gram-negative groups, it was traditionally thought that the groups represent lineages, i.e. the extra membrane only evoved once, such that gram-negative bacteria are more related to one another than to any gram-positive bacteria. While this is true, the classification system breaks down in some cases, with lineage groupings not matching the staining result. Thus, gram-staining cannot be reliably used to assess familial relationships of bacteria. Staining gives reliable information about the composition of the cell membrane, distinguishing between the presence or absence of an outer lipid membrane.
Of these two structurally distinct groups of prokaryotic organisms, monoderm prokaryotes are thought to be ancestral. Based upon a number of different observations including that the gram-positive bacteria are the major reactors to antibiotics and that gram-negative bacteria are, in general, resistant to them, it has been proposed that the outer cell membrane in gram-negative bacteria evolved as a protective mechanism against antibiotic selection pressure; some bacteria such as Deinococcus, which stain gram-positive due to the presence of a thick peptidoglycan layer, but possess an outer cell membrane are suggested as intermediates in the transition between monoderm and diderm bacteria. The diderm bacteria can be further differentiated between simple diderms lacking lipopolysaccharide; the conventional LPS-diderm group of gram-negative bacteria are uniquely identified by a few conserved signature indel in the HSP60 protein. In addition, a number of bacterial taxa that are either part of the phylum Firmicutes or branches in its proximity are found to possess a diderm cell structure.
They lack the GroEL signature. The presence of this CSI in all se
Listeria monocytogenes is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the absence of oxygen, it can grow and reproduce inside the host's cells and is one of the most virulent foodborne pathogens, with 20 to 30% of foodborne listeriosis infections in high-risk individuals may be fatal. Responsible for an estimated 1,600 illnesses and 260 deaths in the United States annually, listeriosis ranks third in total number of deaths among foodborne bacterial pathogens, with fatality rates exceeding Salmonella spp. and Clostridium botulinum. In the European Union, listeriosis follows an upward trend that began in 2008, causing 2,161 confirmed cases and 210 reported deaths in 2014, 16% more than in 2013. Listeriosis mortality rates in the US are higher in the EU than for other foodborne pathogens. Listeria monocytogenes is a Gram-positive bacterium, in the division Firmicutes, named after Joseph Lister, its ability to grow at temperatures as low as 0°C permits multiplication at typical refrigeration temperatures increasing its ability to evade control in human foodstuffs.
Motile via flagella at 30°C and below, but not at 37°C, L. monocytogenes can instead move within eukaryotic cells by explosive polymerization of actin filaments. Studies suggest. Clinical diseases due to L. monocytogenes are more recognized by veterinarians as meningoencephalitis in ruminants. See: listeriosis in animals. Due to its frequent pathogenicity, causing meningitis in newborns, pregnant mothers are advised not to eat soft cheeses such as Brie, Camembert and queso blanco fresco, which may be contaminated with and permit growth of L. monocytogenes. It is the third-most common cause of meningitis in newborns. Listeria monocytogenes can infect the brain, spinal-cord membranes and/or the bloodstream of the host through the ingestion of contaminated food such as unpasteurized dairy or raw foods. L. monocytogenes is a Gram-positive, non-spore-forming, facultatively anaerobic, rod-shaped bacterium. It is catalase-positive and oxidase-negative, expresses a beta hemolysin, which causes destruction of red blood cells.
This bacterium exhibits characteristic tumbling motility. Although L. monocytogenes is motile by means of peritrichous flagella at room temperature, the organism does not synthesize flagella at body temperatures. The genus Listeria belongs to the class Bacilli and the order Bacillales, which includes Bacillus and Staphylococcus. Listeria contains 10 species: L. fleischmannii, L. grayi, L. innocua, L. ivanovii, L. marthii, L. monocytogenes, L. rocourtiae, L. seeligeri, L. weihenstephanensis, L. welshimeri. L. denitrificans thought to be part of the genus Listeria, was reclassified into the new genus Jonesia. Both L. ivanovii and L. monocytogenes are pathogenic in mice, but only L. monocytogenes is associated with human illness. The 13 serotypes of L. monocytogenes can cause disease, but more than 90% of human isolates belong to only three serotypes: 1/2a, 1/2b, 4b. L. monocytogenes serotype 4b strains are responsible for 33 to 35% of sporadic human cases worldwide and for all major foodborne outbreaks in Europe and North America since the 1980s.
L. monocytogenes was first described by E. G. D. Murray in 1924 based on six cases of sudden death in young rabbits, published a description with his colleagues in 1926. Murray referred to the organism as Bacterium monocytogenes before Harvey Pirie changed the genus name to Listeria in 1940. Although clinical descriptions of L. monocytogenes infection in both animals and humans were published in the 1920s, it was not recognized as a significant cause of neonatal infection and meningitis until 1952 in East Germany. Listeriosis in adults was associated with patients living with compromised immune systems, such as individuals taking immunosuppressant drugs and corticosteroids for malignancies or organ transplants, those with HIV infection. L. Monocytogenes was not identified as a cause of foodborne illness until 1981, however. An outbreak of listeriosis in Halifax, Nova Scotia, involving 41 cases and 18 deaths in pregnant women and neonates, was epidemiologically linked to the consumption of coleslaw containing cabbage, contaminated with L. monocytogenes-contaminated sheep manure.
Since a number of cases of foodborne listeriosis have been reported, L. monocytogenes is now recognized as an important hazard in the food industry. Invasive infection by L. monocytogenes causes the disease listeriosis. When the infection is not invasive, any illness as a consequence of infection is termed febrile gastroenteritis; the manifestations of listeriosis include sepsis, encephalitis, corneal ulcer and intrauterine or cervical infections in pregnant women, which may result in spontaneous abortion or stillbirth. Surviving neonates of fetomaternal listeriosis may suffer granulomatosis infantiseptica — pyogenic granulomas distributed over the whole body — and may suffer from physical retardation. Influenza-like symptoms, including persistent fever precede the onset of the aforementioned disorders. Gastrointestinal symptoms, such as nausea and diarrhea, may precede more serious forms of listeriosis or may be the only symptoms expressed. Gastrointestinal symptoms were epidemiologically associated with use of antacids or cimetidine.
The onset time to serious forms of listeriosis is unknown, but may ra
Alphaproteobacteria is a class of bacteria in the phylum Proteobacteria. Its members are diverse and possess few commonalities, but share a common ancestor. Like all Proteobacteria, its members are gram-negative and some of its intracellular parasitic members lack peptidoglycan and are gram variable; the Alphaproteobacteria is a diverse taxon and comprises several phototrophic genera, several genera metabolising C1-compounds, symbionts of plants, endosymbionts of arthropods and intracellular pathogens. Moreover, the class includes the protomitochondrion, the bacterium, engulfed by the eukaryotic ancestor and gave rise to the mitochondria, which are organelles in eukaryotic cells. A species of technological interest is Rhizobium radiobacter: scientists use this species to transfer foreign DNA into plant genomes. Aerobic anoxygenic phototrophic bacteria, such as Pelagibacter ubique, are alphaproteobacteria that are a distributed and may constitute over 10% of the open ocean microbial community.
There is some disagreement on the phylogeny of the orders for the location of the Pelagibacterales, but overall there is some consensus. The discord stems from the large difference in gene content and the large difference in GC-richness between members of several orders. Pelagibacterales and Holosporales contain species with AT-rich genomes, it has been argued that it could be a case of convergent evolution that would result in an artefactual clustering. However, several studies disagree. Furthermore, it has been found that the GC-content of ribosomal RNA little reflects the GC-content of the genome. One example of this atypical decorrelation of ribosomal GC-content with phylogeny is that members of the Holosporales have a much higher ribosomal GC-content than members of the Pelagibacterales and Rickettsiales though they are more related to species with high genomic GC-contents than to members of the latter two orders; the Class Alphaproteobacteria is divided into three subclasses Magnetococcidae and Caulobacteridae.
The basal group is Magnetococcidae, composed by a large diversity of magnetotactic bacteria, but only one is described, Magnetococcus marinus. The Rickettsidae is composed of the intracellular Rickettsiales and the free-living Pelagibacterales; the Caulobacteridae is composed of the Holosporales, Sphingomonadales, Caulobacterales, Kordiimonadales and Sneathiellales. Comparative analyses of the sequenced genomes have led to discovery of many conserved insertion-deletions in distributed proteins and whole proteins that are distinctive characteristics of either all Alphaproteobacteria, or their different main orders and families; these molecular signatures provide novel means for the circumscription of these taxonomic groups and for identification/assignment of new species into these groups. Phylogenetic analyses and conserved indels in large numbers of other proteins provide evidence that Alphaproteobacteria have branched off than most other phyla and Classes of Bacteria except Betaproteobacteria and Gammaproteobacteria.
The accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature and National Center for Biotechnology Information and the phylogeny is based on 16S rRNA-based LTP release 106 by'The All-Species Living Tree' Project Notes:♠ Strains found at the National Center for Biotechnology Information but not listed in the List of Prokaryotic names with Standing in Nomenclature Although only a few studies have been reported on natural genetic transformation in the Alphaproteobacteria, this process has been described in Agrobacterium tumefaciens, Methylobacterium organophilum, Bradyrhizobium japonicum. Natural genetic transformation is a sexual process involving DNA transfer from one bacterial cell to another through the intervening medium, the integration of the donor sequence into the recipient genome by homologous recombination. Alphaproteobacteria at the US National Library of Medicine Medical Subject Headings Bacterial Phylogeny Webpage: Alpha Proteobacteria
International Standard Serial Number
An International Standard Serial Number is an eight-digit serial number used to uniquely identify a serial publication, such as a magazine. The ISSN is helpful in distinguishing between serials with the same title. ISSN are used in ordering, interlibrary loans, other practices in connection with serial literature; the ISSN system was first drafted as an International Organization for Standardization international standard in 1971 and published as ISO 3297 in 1975. ISO subcommittee TC 46/SC 9 is responsible for maintaining the standard; when a serial with the same content is published in more than one media type, a different ISSN is assigned to each media type. For example, many serials are published both in electronic media; the ISSN system refers to these types as electronic ISSN, respectively. Conversely, as defined in ISO 3297:2007, every serial in the ISSN system is assigned a linking ISSN the same as the ISSN assigned to the serial in its first published medium, which links together all ISSNs assigned to the serial in every medium.
The format of the ISSN is an eight digit code, divided by a hyphen into two four-digit numbers. As an integer number, it can be represented by the first seven digits; the last code digit, which may be 0-9 or an X, is a check digit. Formally, the general form of the ISSN code can be expressed as follows: NNNN-NNNC where N is in the set, a digit character, C is in; the ISSN of the journal Hearing Research, for example, is 0378-5955, where the final 5 is the check digit, C=5. To calculate the check digit, the following algorithm may be used: Calculate the sum of the first seven digits of the ISSN multiplied by its position in the number, counting from the right—that is, 8, 7, 6, 5, 4, 3, 2, respectively: 0 ⋅ 8 + 3 ⋅ 7 + 7 ⋅ 6 + 8 ⋅ 5 + 5 ⋅ 4 + 9 ⋅ 3 + 5 ⋅ 2 = 0 + 21 + 42 + 40 + 20 + 27 + 10 = 160 The modulus 11 of this sum is calculated. For calculations, an upper case X in the check digit position indicates a check digit of 10. To confirm the check digit, calculate the sum of all eight digits of the ISSN multiplied by its position in the number, counting from the right.
The modulus 11 of the sum must be 0. There is an online ISSN checker. ISSN codes are assigned by a network of ISSN National Centres located at national libraries and coordinated by the ISSN International Centre based in Paris; the International Centre is an intergovernmental organization created in 1974 through an agreement between UNESCO and the French government. The International Centre maintains a database of all ISSNs assigned worldwide, the ISDS Register otherwise known as the ISSN Register. At the end of 2016, the ISSN Register contained records for 1,943,572 items. ISSN and ISBN codes are similar in concept. An ISBN might be assigned for particular issues of a serial, in addition to the ISSN code for the serial as a whole. An ISSN, unlike the ISBN code, is an anonymous identifier associated with a serial title, containing no information as to the publisher or its location. For this reason a new ISSN is assigned to a serial each time it undergoes a major title change. Since the ISSN applies to an entire serial a new identifier, the Serial Item and Contribution Identifier, was built on top of it to allow references to specific volumes, articles, or other identifiable components.
Separate ISSNs are needed for serials in different media. Thus, the print and electronic media versions of a serial need separate ISSNs. A CD-ROM version and a web version of a serial require different ISSNs since two different media are involved. However, the same ISSN can be used for different file formats of the same online serial; this "media-oriented identification" of serials made sense in the 1970s. In the 1990s and onward, with personal computers, better screens, the Web, it makes sense to consider only content, independent of media; this "content-oriented identification" of serials was a repressed demand during a decade, but no ISSN update or initiative occurred. A natural extension for ISSN, the unique-identification of the articles in the serials, was the main demand application. An alternative serials' contents model arrived with the indecs Content Model and its application, the digital object identifier, as ISSN-independent initiative, consolidated in the 2000s. Only in 2007, ISSN-L was defined in the
Shigella is a genus of Gram-negative, facultative aerobic, non-spore-forming, rod-shaped bacteria genetically related to E. coli. The genus is named after Kiyoshi Shiga, who first discovered it in 1897; the causative agent of human shigellosis, Shigella causes disease in primates, but not in other mammals. It is only found in humans and gorillas. During infection, it causes dysentery. Shigella is one of the leading bacterial causes of diarrhea worldwide, causing an estimated 80–165 million cases; the number of deaths it causes each year is estimated at between 74,000 and 600,000. It is one of the top four pathogens that cause moderate-to-severe diarrhea in African and South Asian children. Shigella species are classified by three serogroups and one serotype: Serogroup A: S. dysenteriae Serogroup B: S. flexneri Serogroup C: S. boydii Serogroup D: S. sonnei Groups A–C are physiologically similar. Three Shigella groups are the major disease-causing species: S. flexneri is the most isolated species worldwide, accounts for 60% of cases in the developing world.
Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with those of E. coli K12 strain MG1655. Phylogenetic studies indicate Shigella is more appropriately treated as subgenus of Escherichia, that certain strains considered E. coli—such as E. coli O157:H7—are better placed in Shigella. Shigella infection is by ingestion. Depending on the health of the host, fewer than 100 bacterial cells can be enough to cause an infection. Shigella species invade the epithelial lining of the colon, causing severe inflammation and death of the cells lining the colon; this inflammation results in the diarrhea and dysentery that are the hallmarks of Shigella infection. Some strains of Shigella produce toxins. S. flexneri strains produce ShET2, which may contribute to diarrhea. S. dysenteriae strains produce the enterotoxin Shiga toxin, similar to the verotoxin produced by enterohemorrhagic E. coli. Both Shiga toxin and verotoxin are associated with causing fatal hemolytic-uremic syndrome.
Shigella species invade the host through the M-cells interspersed in the gut epithelia of the small intestine, as they do not interact with the apical surface of epithelial cells, preferring the basolateral side. Shigella uses a type-III secretion system, which acts as a biological syringe to translocate toxic effector proteins to the target human cell; the effector proteins can alter the metabolism of the target cell, for instance leading to the lysis of vacuolar membranes or reorganization of actin polymerization to facilitate intracellular motility of Shigella bacteria inside the host cell. For instance, the IcsA effector protein triggers actin reorganization by N-WASP recruitment of Arp2/3 complexes, helping cell-to-cell spread. After invasion, Shigella cells multiply intracellularly and spread to neighboring epithelial cells, resulting in tissue destruction and characteristic pathology of shigellosis; the most common symptoms are diarrhea, nausea, stomach cramps, flatulence. It is commonly known to cause large and painful bowel movements.
The stool may contain mucus, or pus. Hence, Shigella cells may cause dysentery. In rare cases, young children may have seizures. Symptoms can take as long as a week to appear, but most begin two to four days after ingestion. Symptoms last for several days, but can last for weeks. Shigella is implicated as one of the pathogenic causes of reactive arthritis worldwide. Apocholate citrate agar Diarrhea Enterotoxigenic E. coli Gastroenteritis Traveler's diarrhea Shigella genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID Vaccine Resource Library: Shigellosis and enterotoxigenic Escherichia coli US Centers for Disease Control and Prevention. Shigella - Shigellosis
Glutamine is an α-amino acid, used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide, it is classified as a polar amino acid. It is non-essential and conditionally essential in humans, meaning the body can synthesize sufficient amounts of it, but in some instances of stress, the body's demand for glutamine increases, glutamine must be obtained from the diet, it is encoded by the codons CAA and CAG. In human blood, glutamine is the most abundant free amino acid; the dietary sources of glutamine includes the protein-rich foods like beef, fish, dairy products, vegetables like beans, cabbage, carrots, vegetable juices and in wheat, Brussels sprouts, celery and fermented foods like miso. Glutamine plays a role in a variety of biochemical functions: Protein synthesis, as any other of the 20 proteinogenic amino acids Lipid synthesis by cancer cells. Regulation of acid-base balance in the kidney by producing ammonium Cellular energy, as a source, next to glucose Nitrogen donation for many anabolic processes, including the synthesis of purines Carbon donation, as a source, refilling the citric acid cycle Nontoxic transporter of ammonia in the blood circulation Precursor to the neurotransmitter glutamateOn the level of tissue, glutamine plays a role in maintaining the normal integrity of the intestinal mucosa.
But randomised trials provide no evidence of any benefit of nutritional supplementation. Glutamine is synthesized by the enzyme glutamine synthetase from ammonia; the most relevant glutamine-producing tissue is the muscle mass, accounting for about 90% of all glutamine synthesized. Glutamine is released, in small amounts, by the lungs and brain. Although the liver is capable of relevant glutamine synthesis, its role in glutamine metabolism is more regulatory than producing, since the liver takes up large amounts of glutamine derived from the gut; the most eager consumers of glutamine are the cells of intestines, the kidney cells for the acid-base balance, activated immune cells, many cancer cells. Glutamine is the most abundant occurring, nonessential amino acid in the human body, one of the few amino acids that can directly cross the blood–brain barrier. Humans obtain glutamine through catabolism of proteins in foods. In states where tissue is being built or repaired, like growth of babies, or healing from wounds or severe illness, glutamine becomes conditionally essential.
In 2017, the U. S. Food and Drug Administration approved L-glutamine oral powder, marketed as Endari, to reduce severe complications of sickle cell disease in people aged 5 years and older with the disorder. Glutamine is marketed as medical food and is prescribed when a medical professional believes a person in their care needs supplementary glutamine due to metabolic demands beyond what can be met by endogenous synthesis or diet. Glutamine is safe in preterm infants. Although glutamine is metabolized to glutamate and ammonia, both of which have neurological effects, their concentrations are not increased much, no adverse neurological effects were detected; the observed safe level for supplemental L-glutamine in normal healthy adults is 14 g/day. Adverse effects of glutamine have been described for people receiving home parenteral nutrition and those with liver-function abnormalities. Although glutamine has no effect on the proliferation of tumor cells, it is still possible that glutamine supplementation may be detrimental in some cancer types.
Ceasing glutamine supplementation in people adapted to high consumption may initiate a withdrawal effect, raising the risk of health problems such as infections or impaired integrity of the intestine. Glutamine can exist in either of two enantiomeric forms, D-glutamine; the L-form is found in nature. Glutamine contains an α-amino group, in the protonated −NH3+ form under biological conditions and a carboxylic acid group, in the deprotonated −COO− form, known as carboxylate, under physiological conditions. Glutamine mouthwash may be useful to prevent oral mucositis in people undergoing chemotherapy but intravenous glutamine does not appear useful to prevent mucositis in the GI tract. Glutamine supplementation was thought to have potential to reduce complications in people who are critically ill or who have had abdominal surgery but this was based on poor quality clinical trials. Supplementation does not appear to be useful in adults or children with Crohn's disease or inflammatory bowel disease, but clinical studies as of 2016 were underpowered.
Supplementation does not appear to have an effect in infants with significant problems of the stomach or intestines. Some athletes use L-glutamine as supplement. Studies support the positive effects of the chronic oral administration of the supplement on the injury and inflammation induced by intense aerobic and exhaustive exercise, but the effects on muscle recovery are unclear. Isoglutamine Glutamine spectra acquired through mass spectroscopy