Glutamine (symbolGln orQ)[3] is anα-amino acid that is used in the biosynthesis ofproteins. Itsside chain is similar to that ofglutamic acid, except the carboxylic acid group is replaced by anamide. It is classified as a charge-neutral, polar amino acid. It is non-essential andconditionally essential in humans, meaning the body can usuallysynthesize sufficient amounts of it, but in some instances of stress, the body's demand for glutamine increases, and glutamine must be obtained from the diet.[4][5] It isencoded by thecodons CAA and CAG. It is named after glutamic acid, which in turn is named after its discovery in cereal proteins,gluten.[6]
The one-letter symbol Q for glutamine was assigned in alphabetical sequence to N forasparagine, being larger by merely onemethylene –CH2– group. Note that P was used for proline, and O was avoided due to similarity with D. The mnemonicQlutamine was also proposed.[6]
Glutamine maintains redox balance by participating inglutathione synthesis and contributing to anabolic processes such as lipid synthesis by reductive carboxylation.[14]
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[15] and is essential for many cellular functions. Examples include the synthesis ofnucleotides andnon-essential amino acids.[16] 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.[17] The highest consumption of glutamine occurs in the cells of the intestines,[7] kidney cells (where it is used for acid-base balance), activated immune cells,[18] and manycancer cells.[8][11][19]
Glutamine synthesis fromglutamate and ammonia is catalyzed by theenzymeglutamine 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.[21] 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 thehepatic portal system.[7]
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 theblood–brain barrier.[7] Humans obtain glutamine throughcatabolism ofproteins in foods they eat.[22] In states where tissue is being built or repaired, like growth of babies, or healing from wounds or severe illness, glutamine becomesconditionally essential.[22]
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In 2017, the U.S.Food and Drug Administration (FDA) approvedL-glutamine oral powder, marketed asEndari, to reduce severe complications ofsickle cell disease in people aged five years and older with the disorder.[1]
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.[1] Subjects were assigned randomly to treatment with L-glutamine oral powder or placebo, and the effect of treatment was evaluated over 48 weeks.[1] 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).[1] 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).[1]
Common side effects of L-glutamine oral powder include constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain and chest pain.[1]
L-glutamine oral powder receivedorphan drug designation.[1] The FDA granted the approval of Endari to Emmaus Medical Inc.[1]
Glutamine is marketed asmedical 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.[23]
Glutamine is safe in adults and in preterm infants.[24] 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.[24] The observed safe level for supplementalL-glutamine in normal healthy adults is 14 g/day.[25]
Adverse effects of glutamine have been described for people receiving home parenteral nutrition and those with liver-function abnormalities.[26]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.[27]
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.[27]
Glutamine can exist in either of twoenantiomeric forms,L-glutamine andD-glutamine. TheL-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.
Glutaminezwitterionic forms at neutral pH: L-glutamine (left) and D-glutamine
Consequences of glutamine depletion in critically ill individuals[28]
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.[29] Supplementation does not appear to have an effect in infants with significant stomach or intestinal disorders.[30]
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^abCorbet C, Feron O (July 2015). Corbet C, Feron O (eds.). "Metabolic and mind shifts: from glucose to glutamine and acetate addictions in cancer".Current Opinion in Clinical Nutrition and Metabolic Care.18 (4):346–353.doi:10.1097/MCO.0000000000000178.PMID26001655.S2CID1478014.
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^Dabrowska K, Skowronska K, Popek M, Obara-Michlewska M, Albrecht J, Zielinska M (2018). "Roles of Glutamate and Glutamine Transport in Ammonia Neurotoxicity: State of the Art and Question Marks".Endocrine, Metabolic & Immune Disorders Drug Targets.18 (4):306–315.doi:10.2174/1871520618666171219124427.PMID29256360.S2CID26569656.
^Welbourne TC (March 1979). "Ammonia production and glutamine incorporation into glutathione in the functioning rat kidney".Canadian Journal of Biochemistry.57 (3):233–237.doi:10.1139/o79-029.PMID436006.
^Shao A, Hathcock JN (April 2008). "Risk assessment for the amino acids taurine, L-glutamine and L-arginine".Regulatory Toxicology and Pharmacology.50 (3):376–399.doi:10.1016/j.yrtph.2008.01.004.PMID18325648.
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