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Glutamine

Skeletal formula of L-glutamine
Ball-and-stick model Space-filling model
Names
IUPAC name Glutamine
Other names L-Glutamine (levo)glutamide 2,5-Diamino-5-oxopentanoic acid 2-Amino-4-carbamoylbutanoic acid Endari
Identifiers
CAS Number	56-85-9
3D model (JSmol)	Interactive image Zwitterion: Interactive image
Abbreviations	Gln, Q
ChEBI	CHEBI:18050
ChEMBL	ChEMBL930
ChemSpider	5746
DrugBank	DB00130
ECHA InfoCard	100.000.266
EC Number	200-292-1
IUPHAR/BPS	723
KEGG	C00303
PubChem CID	5961
UNII	0RH81L854J
CompTox Dashboard (EPA)	DTXSID1023100
InChI InChI=1S/C5H10N2O3/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H2,7,8)(H,9,10)/t3-/m0/s1Key: ZDXPYRJPNDTMRX-VKHMYHEASA-N
SMILES O=C(N)CCC(N)C(=O)O Zwitterion: O=C(N)CCC()C(=O)
Properties
Chemical formula	C5H10N2O3
Molar mass	146.146 g·mol
Melting point	decomposes around 185°C
Solubility in water	soluble
Acidity (pKa)	2.2 (carboxyl), 9.1 (amino)
Chiral rotation (D)	+6.5º (H2O, c = 2)
Pharmacology
ATC code	A16AA03 (WHO)
Supplementary data page
Glutamine (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references

L-glutamine oral powder

Clinical data
Trade names	Endari, Nutrestore
AHFS/Drugs.com	Monograph
MedlinePlus	a617035
License data	US DailyMed: Glutamine
Routes of administration	By mouth
Drug class	Gastrointestinal agent
ATC code	A16AA03 (WHO)
Legal status
Legal status	US: ℞-only
Identifiers
IUPAC name (S)-2,5-diamino-5-oxopentanoic acid
CAS Number	56-85-9
PubChem CID	5961
DrugBank	DB00130
ChemSpider	5746
UNII	0RH81L854J
KEGG	D00015 C00064
ChEBI	CHEBI:58359
ChEMBL	ChEMBL930
PDB ligand	GLN (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID1023100
ECHA InfoCard	100.000.266
Chemical and physical data
Formula	C5H10N2O3
Molar mass	146.146 g·mol
3D model (JSmol)	Interactive image
SMILES C(CC(=O)N)C(C(=O)O)N
InChI InChI=1S/C5H10N2O3/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H2,7,8)(H,9,10)/t3-/m0/s1 Key:ZDXPYRJPNDTMRX-VKHMYHEASA-N
Data page
Glutamine (data page)

Glutamine (symbol Gln or Q) 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. 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.

In human blood, glutamine is the most abundant free amino acid.

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.

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.
• 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.
• Integrity of healthy intestinal mucosa, though small randomized trials have shown no benefit in Crohn's disease.

Roles in metabolism

Glutamine maintains redox balance by participating in glutathione synthesis and contributing to anabolic processes such as lipid synthesis by reductive carboxylation.

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 and is essential for many cellular functions. Examples include the synthesis of nucleotides and non-essential amino acids. 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. 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, and many cancer cells.

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.

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. 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.

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. Humans obtain glutamine through catabolism of proteins in foods they eat. In states where tissue is being built or repaired, like growth of babies, or healing from wounds or severe illness, glutamine becomes conditionally essential.

Sickle cell disease

This section is missing information about (possible) mechanism of action, pharmacokinetics in PMID 31985279. Please expand the section to include this information. Further details may exist on the talk page. (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.

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.

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.

Safety

Glutamine is safe in adults and in preterm infants. 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.

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 very high consumption may initiate a withdrawal effect, raising the risk of health problems such as infections or impaired integrity of the intestine.

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.

Research

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 from weight training are unclear.

Stress conditions for plants (drought, injury, soil salnity) cause the synthesis of such plant enzymes as superoxide dismutase, L-ascorbate oxidase, and Delta 1 DNA polymerase. Limiting this process, initiated by the conditions of strong soil salinity can be achieved by administering exogenous glutamine to plants. The decrease in the level of expression of genes responsible for the synthesis of superoxide dismutase increases with the increase in glutamine concentration.

See also

• Isoglutamine
• Trinucleotide repeat disorder
• PolyQ tract

References

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External links

• Glutamine spectra acquired through mass spectroscopy

v t e Encoded (proteinogenic) amino acids
General topics	Protein Peptide Genetic code
By properties	Aliphatic Branched-chain amino acids (Valine Isoleucine Leucine) Methionine Alanine Proline Glycine Aromatic Histidine Tyrosine Tryptophan Phenylalanine Polar, uncharged Asparagine Glutamine Serine Threonine Positive charge (pKa) Lysine (≈10.8) Arginine (≈12.5) Histidine (≈6.1) Pyrrolysine Negative charge (pKa) Aspartic acid (≈3.9) Glutamic acid (≈4.1) Selenocysteine (≈5.4) Cysteine (≈8.3) Tyrosine (≈10.1)
Amino acids types: Encoded (proteins) Essential Non-proteinogenic Ketogenic Glucogenic Secondary amino Imino acids D-amino acids Dehydroamino acids

• Medicine

• Carboxamides
• Dietary supplements
• Glucogenic amino acids
• Proteinogenic amino acids
• Medical food
• Orphan drugs
• Glutamate (neurotransmitter)
• Neurotransmitter precursors