Glutamine

File:Glutamine-spin.gif

Glutamine ball and stick model spinning

Glutamine (symbol Gln or Q)<ref>Template:Cite web</ref> is an α-amino acid that is 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 charge-neutral, polar amino acid. It is non-essential and conditionally essential in humans, meaning the body can usually synthesize 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.<ref>Template:Cite book</ref><ref>Template:Cite journal</ref> It is encoded by the codons CAA and CAG. It is named after glutamic acid, which in turn is named after its discovery in cereal proteins, gluten.<ref name = "Saffran_1998">Template:Cite journal</ref>

In human blood, glutamine is the most abundant free amino acid.<ref name="Brosnan">Template:Cite journalTemplate:Open access</ref>

The dietary sources of glutamine include especially the protein-rich foods like beef, chicken, fish, dairy products, eggs, vegetables like beans, beets, cabbage, spinach, carrots, parsley, vegetable juices and also in wheat, papaya, Brussels sprouts, celery, kale and fermented foods like miso.

The one-letter symbol Q for glutamine was assigned in alphabetical sequence to N for asparagine, being larger by merely one methylene –CH2– group. Note that P was used for proline, and O was avoided due to similarity with D. The mnemonic Qlutamine was also proposed.<ref name = "Saffran_1998" />

Functions

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.<ref name="pmid26001655">Template:Cite journal</ref>
• Regulation of acid-base balance in the kidney by producing ammonium<ref>Template:Cite book</ref>
• Cellular energy, as a source, next to glucose<ref>Template:Cite journal</ref>
• Nitrogen donation for many anabolic processes, including the synthesis of purines<ref name="Brosnan"/>
• Carbon donation, as a source, refilling the citric acid cycle<ref name="Yuneva">Template:Cite journal</ref>
• Nontoxic transporter of ammonia in the blood circulation.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Roles in metabolism

Glutamine maintains redox balance by participating in glutathione synthesis and contributing to anabolic processes such as lipid synthesis by reductive carboxylation.<ref>Template:Cite journal</ref>

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<ref>Template:Cite journal</ref> and is essential for many cellular functions. Examples include the synthesis of nucleotides and non-essential amino acids.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> The highest consumption of glutamine occurs in the cells of the intestines,<ref name="Brosnan"/> kidney cells (where it is used for acid-base balance), activated immune cells,<ref>Template:Cite journal</ref> and many cancer cells.<ref name="pmid26001655"/><ref name="Yuneva"/><ref>Template:Cite journal</ref>

Production

Glutamine is produced industrially using mutants of Brevibacterium flavum, which gives ca. 40 g/L in 2 days using glucose as a carbon source.<ref>Template:Ullmann</ref>

Biosynthesis

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.<ref>Template:Cite journal</ref> 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.<ref name="Brosnan"/>

Uses

Nutrition

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.<ref name="Brosnan"/> Humans obtain glutamine through catabolism of proteins in foods they eat.<ref name=Watford2015rev>Template:Cite journal</ref> In states where tissue is being built or repaired, like growth of babies, or healing from wounds or severe illness, glutamine becomes conditionally essential.<ref name=Watford2015rev/>

Sickle cell disease

Template:Missing information 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.<ref name="FDA2017Glu">Template:Cite press release Template:PD-notice</ref>

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.<ref name="FDA2017Glu" /> Subjects were assigned randomly to treatment with L-glutamine oral powder or placebo, and the effect of treatment was evaluated over 48 weeks.<ref name="FDA2017Glu" /> 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).<ref name="FDA2017Glu" /> 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).<ref name="FDA2017Glu" />

Common side effects of L-glutamine oral powder include constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain and chest pain.<ref name="FDA2017Glu" />

L-glutamine oral powder received orphan drug designation.<ref name="FDA2017Glu" /> The FDA granted the approval of Endari to Emmaus Medical Inc.<ref name="FDA2017Glu" />

Medical food

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.<ref>Template:Cite web</ref>

Safety

Glutamine is safe in adults and in preterm infants.<ref name="pmid11533313">Template:Cite journal</ref> 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.<ref name="pmid11533313"/> The observed safe level for supplemental L-glutamine in normal healthy adults is 14 g/day.<ref name="pmid18325648">Template:Cite journal</ref>

Adverse effects of glutamine have been described for people receiving home parenteral nutrition and those with liver-function abnormalities.<ref name="pmid11451714">Template:Cite journal</ref> 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.<ref name="pmid22990615">Template:Cite journal</ref>

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.<ref name="pmid22990615"/>

Structure

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

Glutamine zwitterionic forms at neutral pH: L-glutamine (left) and D-glutamine

Research

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Consequences of glutamine depletion in critically ill individuals<ref name="pmid26495301">Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref> Supplementation does not appear to have an effect in infants with significant stomach or intestinal disorders.<ref>Template:Cite journal</ref>

See also

• Isoglutamine
• Trinucleotide repeat disorder
• PolyQ tract

External links

• Glutamine spectra acquired through mass spectroscopy