Glutamine is a nonessential amino acid and is the most abundant amino acid in the body. It is formed from glutamate using the enzyme glutamine synthetase. Approximately 80% of glutamine is found in the skeletal muscle, and this concentration is 30 times higher than the amount of glutamine found in human plasma. Although glucose is used as fuel for many tissues in the body, glutamine is the main fuel source for a large number of cells including lymphocytes, neutrophils, macrophages, and enterocytes.
Glutamine is necessary for many physiologic processes including:
- growth of fibroblasts, lymphocytes, and enterocytes
- protein synthesis
- muscle growth
- immune function
- glutathione formation
- nucleotide synthesis
- apoptosis prevention
- regulation of acid-base homeostasis
- glutamate metabolism
- inter-organ nitrogen exchange via ammonia transport
- energy generation (ATP)
Tapiero H, Mathé G, Couvreur P, Tew KD. II. Glutamine and glutamate. Biomed Pharmacother. 2002;56(9):446-457.
- Cruzat V, Macedo Rogero M, Noel Keane K, Curi R, Newsholme P. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients. 2018;10(11).
- Nägeli M, Fasshauer M, Sommerfeld J, Fendel A, Brandi G, Stover JF. Prolonged continuous intravenous infusion of the dipeptide L-alanine- L-glutamine significantly increases plasma glutamine and alanine without elevating brain glutamate in patients with severe traumatic brain injury. Crit Care. 2014;18(4):R139.
- Cruzat V, Macedo Rogero M, Noel Keane K, Curi R, Newsholme P. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients. 2018;10(11):156462
- Jurgens P, Schwartau M, Doehn M. [Disorders of amino acid metabolism in a patient with identified thiamine deficiency]. Infusionstherapie klinische Ernahrung. 1982;9(6):312-316.
- Garg U, Smith LD. Biomarkers Inborn Errors of Metabolism: Clinical Aspects and Laboratory Determination. Elsevier; 2017.
Decreased protein intake, GI malabsorption, and maldigestion can contribute to overall lower amino acid levels. However, given the extensive role of glutamine throughout the body, increased metabolic demand can also result in lower levels. Glutamine is considered a conditionally essential amino acid in critically ill patients. Endogenous glutamine synthesis does not meet the body’s demands in catabolic conditions including cancer, sepsis, infections, surgeries, traumas, and during intense and prolonged physical exercise. Low plasma glutamine is associated with increased mortality and functional impairment in critically ill patients. Glutamine administration reduces infection-related morbidity, decreases mortality during the intensive care phase, and shortens the length of hospitalization.
High protein intake may contribute to higher levels. It should also be noted that glutamine is available as a nutraceutical supplement. Elevations can also be seen with supplementation. The metabolism of glutamine requires several cofactors, such as NADPH and vitamin B1.
Functional deficiencies of vitamin and mineral cofactors can also elevate levels. There is literature to suggest vitamin B1 supplementation lowers elevated levels of glutamine, as well as other amino acids in thiamine deficiency. Because of the relationship of glutamine and glutamate to both the Cahill Cycle and Urea Cycle, elevations of glutamine are associated with hyperammonemia due to increased production of glutamine from glutamate.
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