glutamine

Glutamine plays a role in a variety of biochemical functions:

• Protein synthesis, as any other of the 20 proteinogenic amino acids
• Lipid synthesis, especially by cancer cells.{{cite journal | vauthors = Corbet C, Feron O | title = Metabolic and mind shifts: from glucose to glutamine and acetate addictions in cancer | journal = Current Opinion in Clinical Nutrition and Metabolic Care | volume = 18 | issue = 4 | pages = 346–353 | date = July 2015 | pmid = 26001655 | doi = 10.1097/MCO.0000000000000178 | s2cid = 1478014 | veditors = Corbet C, Feron O }}
• Regulation of acid-base balance in the kidney by producing ammonium{{cite book | vauthors = Hall JE, Guyton AC |title=Textbook of Medical Physiology |edition = 11th |publisher=Elsevier Saunders |location=St. Louis, Mo |year=2006 |page=393 |isbn=978-0-7216-0240-0}}
• Cellular energy, as a source, next to glucose{{cite journal | vauthors = Aledo JC | title = Glutamine breakdown in rapidly dividing cells: waste or investment? | journal = BioEssays | volume = 26 | issue = 7 | pages = 778–785 | date = July 2004 | pmid = 15221859 | doi = 10.1002/bies.20063 }}
• Nitrogen donation for many anabolic processes, including the synthesis of purines
• Carbon donation, as a source, refilling the citric acid cycle{{cite journal | vauthors = Yuneva M, Zamboni N, Oefner P, Sachidanandam R, Lazebnik Y | title = Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells | journal = The Journal of Cell Biology | volume = 178 | issue = 1 | pages = 93–105 | date = July 2007 | pmid = 17606868 | pmc = 2064426 | doi = 10.1083/jcb.200703099 }}
• Nontoxic transporter of ammonia in the blood circulation.{{cite journal | vauthors = Zielińska M, Albrecht J, Popek M | title = Dysregulation of Astrocytic Glutamine Transport in Acute Hyperammonemic Brain Edema | journal = Frontiers in Neuroscience | volume = 16 | pages = 874750 | date = 2022 | pmid = 35733937 | pmc = 9207324 | doi = 10.3389/fnins.2022.874750 | doi-access = free }}{{cite journal | vauthors = Dabrowska K, Skowronska K, Popek M, Obara-Michlewska M, Albrecht J, Zielinska M | title = Roles of Glutamate and Glutamine Transport in Ammonia Neurotoxicity: State of the Art and Question Marks | journal = Endocrine, Metabolic & Immune Disorders Drug Targets | volume = 18 | issue = 4 | pages = 306–315 | date = 2018 | pmid = 29256360 | doi = 10.2174/1871520618666171219124427 | s2cid = 26569656 }}

Glutamine maintains redox balance by participating in glutathione synthesis and contributing to anabolic processes such as lipid synthesis by reductive carboxylation.{{cite journal | vauthors = Jiang L, Shestov AA, Swain P, Yang C, Parker SJ, Wang QA, Terada LS, Adams ND, McCabe MT, Pietrak B, Schmidt S, Metallo CM, Dranka BP, Schwartz B, DeBerardinis RJ | title = Reductive carboxylation supports redox homeostasis during anchorage-independent growth | journal = Nature | volume = 532 | issue = 7598 | pages = 255–258 | date = April 2016 | pmid = 27049945 | doi = 10.1038/nature17393 | pmc = 4860952 | bibcode = 2016Natur.532..255J }}

Glutamine provides a source of carbon and nitrogen for use in other metabolic processes. Glutamine is present in serum at higher concentrations than other amino acids{{cite journal | vauthors = Welbourne TC | title = Ammonia production and glutamine incorporation into glutathione in the functioning rat kidney | journal = Canadian Journal of Biochemistry | volume = 57 | issue = 3 | pages = 233–237 | date = March 1979 | pmid = 436006 | doi = 10.1139/o79-029 }} and is essential for many cellular functions. Examples include the synthesis of nucleotides and non-essential amino acids.{{cite journal | vauthors = DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB | title = Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 49 | pages = 19345–19350 | date = December 2007 | pmid = 18032601 | doi = 10.1073/pnas.0709747104 | pmc = 2148292 | bibcode = 2007PNAS..10419345D | doi-access = free }} One of the most important functions of glutamine is its ability to be converted into α-KG, which helps to maintain the flow of the tricarboxylic acid cycle, generating ATP via the electron carriers NADH and FADH₂.{{cite journal | vauthors = DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB | title = The biology of cancer: metabolic reprogramming fuels cell growth and proliferation | language = English | journal = Cell Metabolism | volume = 7 | issue = 1 | pages = 11–20 | date = January 2008 | pmid = 18177721 | doi = 10.1016/j.cmet.2007.10.002 | doi-access = free }} The highest consumption of glutamine occurs in the cells of the intestines, kidney cells (where it is used for acid-base balance), activated immune cells,{{cite journal | vauthors = Newsholme P | title = Why is L-glutamine metabolism important to cells of the immune system in health, postinjury, surgery or infection? | journal = The Journal of Nutrition | volume = 131 | issue = 9 Suppl | pages = 2515S–2522S; discussion 2522S–4S | date = September 2001 | pmid = 11533304 | doi = 10.1093/jn/131.9.2515S | doi-access = free }} and many cancer cells.{{cite journal | vauthors = Fernandez-de-Cossio-Diaz J, Vazquez A | title = Limits of aerobic metabolism in cancer cells | language = En | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 13488 | date = October 2017 | pmid = 29044214 | pmc = 5647437 | doi = 10.1038/s41598-017-14071-y | bibcode = 2017NatSR...713488F }}

Glutamine is produced industrially using mutants of Brevibacterium flavum, which gives ca. 40 g/L in 2 days using glucose as a carbon source.{{Ullmann| vauthors = Drauz K, Grayson I, Kleemann A, Krimmer HP, Leuchtenberger W, Weckbecker C |year=2007|title=Amino Acids|doi=10.1002/14356007.a02_057.pub2}}

Glutamine synthesis from glutamate and ammonia is catalyzed by the enzyme glutamine synthetase. The majority of glutamine production occurs in muscle tissue, accounting for about 90% of all glutamine synthesized. Glutamine is also released, in small amounts, by the lungs and brain.{{cite journal | vauthors = Newsholme P, Lima MM, Procopio J, Pithon-Curi TC, Doi SQ, Bazotte RB, Curi R | title = Glutamine and glutamate as vital metabolites | journal = Brazilian Journal of Medical and Biological Research = Revista Brasileira de Pesquisas Medicas e Biologicas | volume = 36 | issue = 2 | pages = 153–163 | date = February 2003 | pmid = 12563517 | doi = 10.1590/S0100-879X2003000200002 | doi-access = free }} Although the liver is capable of glutamine synthesis, its role in glutamine metabolism is more regulatory than productive, as the liver takes up glutamine derived from the gut via the hepatic portal system.

Glutamine is the most abundant naturally occurring, nonessential amino acid in the human body, and one of the few amino acids that can directly cross the blood–brain barrier. Humans obtain glutamine through catabolism of proteins in foods they eat.{{cite journal | vauthors = Watford M | title = Glutamine and glutamate: Nonessential or essential amino acids? | journal = Animal Nutrition | volume = 1 | issue = 3 | pages = 119–122 | date = September 2015 | pmid = 29767158 | pmc = 5945979 | doi = 10.1016/j.aninu.2015.08.008 }} In states where tissue is being built or repaired, like growth of babies, or healing from wounds or severe illness, glutamine becomes conditionally essential.

{{missing information|section|(possible) mechanism of action, pharmacokinetics in {{PMID|31985279}}|date=November 2023}}

In 2017, the U.S. Food and Drug Administration (FDA) approved L-glutamine oral powder, marketed as Endari, to reduce severe complications of sickle cell disease in people aged five years and older with the disorder.{{cite press release|title=FDA approves new treatment for sickle cell disease|url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-sickle-cell-disease |archive-url=https://web.archive.org/web/20191214234411/https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-sickle-cell-disease |url-status=dead |archive-date=14 December 2019 |website=U.S. Food and Drug Administration (FDA)|access-date=10 July 2017|date=7 July 2017}} {{PD-notice}}

The safety and efficacy of L-glutamine oral powder were studied in a randomized trial of subjects ages five to 58 years old with sickle cell disease who had two or more painful crises within the 12 months prior to enrollment in the trial. Subjects were assigned randomly to treatment with L-glutamine oral powder or placebo, and the effect of treatment was evaluated over 48 weeks. Subjects who were treated with L-glutamine oral powder experienced fewer hospital visits for pain treated with a parenterally administered narcotic or ketorolac (sickle cell crises), on average, compared to subjects who received a placebo (median 3 vs. median 4), fewer hospitalizations for sickle cell pain (median 2 vs. median 3), and fewer days in the hospital (median 6.5 days vs. median 11 days). Subjects who received L-glutamine oral powder also had fewer occurrences of acute chest syndrome (a life-threatening complication of sickle cell disease) compared with patients who received a placebo (8.6 percent vs. 23.1 percent).

Common side effects of L-glutamine oral powder include constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain and chest pain.

L-glutamine oral powder received orphan drug designation. The FDA granted the approval of Endari to Emmaus Medical Inc.

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.{{cite web|title=GlutaSolve, NutreStore, SYMPT-X G.I., SYMPT-X Glutamine (glutamine) Drug Side Effects, Interactions, and Medication Information on eMedicineHealth.|url=http://www.emedicinehealth.com/drug-glutamine/article_em.htm|website=eMedicineHealth|access-date=24 January 2017}}

Glutamine is safe in adults and in preterm infants.{{cite journal | vauthors = Garlick PJ | title = Assessment of the safety of glutamine and other amino acids | journal = The Journal of Nutrition | volume = 131 | issue = 9 Suppl | pages = 2556S–2561S | date = September 2001 | pmid = 11533313 | doi = 10.1093/jn/131.9.2556S | doi-access = free }} Although glutamine is metabolized to glutamate and ammonia, both of which have neurological effects, their concentrations are not increased much, and no adverse neurological effects were detected. The observed safe level for supplemental L-glutamine in normal healthy adults is 14 g/day.{{cite journal | vauthors = Shao A, Hathcock JN | title = Risk assessment for the amino acids taurine, L-glutamine and L-arginine | journal = Regulatory Toxicology and Pharmacology | volume = 50 | issue = 3 | pages = 376–399 | date = April 2008 | pmid = 18325648 | doi = 10.1016/j.yrtph.2008.01.004 }}

Adverse effects of glutamine have been described for people receiving home parenteral nutrition and those with liver-function abnormalities.{{cite journal | vauthors = Buchman AL | title = Glutamine: commercially essential or conditionally essential? A critical appraisal of the human data | journal = The American Journal of Clinical Nutrition | volume = 74 | issue = 1 | pages = 25–32 | date = July 2001 | pmid = 11451714 | doi = 10.1093/ajcn/74.1.25 | doi-access = free }}

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.{{cite journal | vauthors = Holecek M | title = Side effects of long-term glutamine supplementation | journal = Journal of Parenteral and Enteral Nutrition | volume = 37 | issue = 5 | pages = 607–616 | date = September 2013 | pmid = 22990615 | doi = 10.1177/0148607112460682 }}

Ceasing glutamine supplementation in people adapted to very 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, L-glutamine and D-glutamine. The L-form is found in nature. Glutamine contains an α-amino group which is in the protonated −NH₃⁺ form under biological conditions and a carboxylic acid group which is in the deprotonated −COO⁻ form, known as carboxylate, under physiological conditions.

File:Betain-Glutamin.png forms at neutral pH: L-glutamine (left) and D-glutamine]]

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Glutamine supplementation was investigated for its possible effects in critically ill people or after abdominal surgery, but the low quality of research prevented conclusions about any effect.{{cite journal | vauthors = Tao KM, Li XQ, Yang LQ, Yu WF, Lu ZJ, Sun YM, Wu FX | title = Glutamine supplementation for critically ill adults | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD010050 | date = September 2014 | volume = 2018 | pmid = 25199493 | pmc = 6517119 | doi = 10.1002/14651858.CD010050.pub2 }} Supplementation does not appear to have an effect in infants with significant stomach or intestinal disorders.{{cite journal | vauthors = Moe-Byrne T, Brown JV, McGuire W | title = Glutamine supplementation to prevent morbidity and mortality in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 4 | pages = CD001457 | date = April 2016 | issue = 4 | pmid = 27089158 | pmc = 7055588 | doi = 10.1002/14651858.CD001457.pub6 | veditors = McGuire W }}

• Isoglutamine
• Trinucleotide repeat disorder
• PolyQ tract

{{reflist}}

• [http://gmd.mpimp-golm.mpg.de/Spectrums/c1bca564-a7ee-4401-85f8-4a3f74dce29c.aspx Glutamine spectra] acquired through mass spectroscopy

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