| DESCRIPTION
L-glutamine is a protein amino acid found in proteins of all life forms. It is classified as a semi-essential or conditionally essential amino acid. This means that under normal circumstances the body can synthesize sufficient L-glutamine to meet physiological demands. However, there are conditions where the body cannot do so. Recently, L-glutamine has come to be regarded as one of the most important of the amino acids when the body is subjected to such metabolic stress situations as trauma (including surgical trauma), cancer, sepsis and burns. Under such conditions, L-glutamine becomes an essential amino acid, and it is therefore very important to ensure adequate intakes of the amino acid in order to meet the increased physiological demands created by these situations.
L-glutamine is the most abundant amino acid in the body, and plasma glutamine levels are the highest of any amino acid. L-glutamine is predominantly synthesized and stored in skeletal muscle. The amino acid L-glutamate is metabolized to L-glutamine in a reaction catalyzed by the enzyme glutamine synthase, a reaction which, in addition to L-glutamate, requires ammonia, ATP and magnesium.
L-glutamine is a very versatile amino acid and participates in many reactions in the body. It is important in the regulation of acid-base balance. L-glutamine allows the kidneys to excrete an acid load, protecting the body against acidosis. This is accomplished by the production of ammonia, which binds hydrogen ions, to produce ammonium cations that are excreted in the urine along with chloride anions. Bicarbonate ions are simultaneously released into the bloodstream. L-glutamine helps protect the body against ammonia toxicity by transporting ammonia, in the form of L-glutamine's amide group, from peripheral tissues to visceral organs, where it can be excreted as ammonium by the kidneys or converted to urea by the liver.
The amide group can also participate in other metabolic activities, as can the amino group of L-glutamine. L-glutamine serves as the most important nitrogen shuttle, supplying nitrogen for metabolic purposes (from glutamine-producing tissues, such as skeletal muscle) to glutamine-consuming tissues.
L-glutamine participates in the formation of purine and pyrimidine nucleotides, amino sugars (such as glucosamine), L-glutamate and other amino acids, nicotinamide adenine dinucleotide and glutathione. It also participates in protein synthesis, energy production and, if necessary, the production of D-glucose and glycogen. Importantly, L-glutamine can serve as the primary respiratory substrate for the production of energy in enterocytes and lymphocytes. L-glutamine is considered an immunonutrient, and supplemental L-glutamine is used in medical foods for such stress situations as trauma, cancer, infections and burns.
The typical dietary intake of L-glutamine is 5 to 10 grams daily. Most dietary L-glutamine comes from animal and plant proteins. Small amounts of free L-glutamine are found in vegetable juices and fermented foods, such as miso and yogurt.
L-glutamine is the amide of L-glutamic acid. Its molecular formula is C5H10N2O3, and its molecular weight is 146.15 daltons. L-glutamine is also known as 2-aminoglutaramic acid, levoglutamide, (S)-2, 5-diamino-5-oxopentaenoic acid and glutamic acid 5-amide. Its one-letter abbreviation is Q, and it is also abbreviated as Gln. The terms L-glutamine and glutamine are used interchangeably. D-glutamine, the stereoisomer of L-glutamine, does not have, as far as is known, biological activity. L-glutamine is not very soluble in water, and aqueous solutions are unstable at temperatures of 22 to 24 degrees Celsius. For these reasons, the more soluble and more stable glutamine dipeptides are used as delivery forms of L-glutamine in total parenteral nutrition (TPN) solutions. See Glutamine Peptides.
ACTIONS AND PHARMACOLOGY
ACTIONS
Supplemental L-glutamine may have immunomodulatory, anticatabolic/anabolic and gastrointestinal mucosal-protective actions. It may also have antioxidant activity.
MECHANISM OF ACTION
Supplemental L-glutamine's possible immunomodulatory role may be accounted for in a number of ways. L-glutamine appears to play a major role in protecting the integrity of the gastrointestinal tract and, in particular, the large intestine. During catabolic states, the integrity of the intestinal mucosa may be compromised with consequent increased intestinal permeability and translocation of Gram-negative bacteria from the large intestine into the body. The demand for L-glutamine by the intestine, as well as by cells such as lymphocytes, appears to be much greater than that supplied by skeletal muscle, the major storage tissue for L-glutamine. L-glutamine is the preferred respiratory fuel for enterocytes, colonocytes and lymphocytes. Therefore, supplying supplemental L-glutamine under these conditions may do a number of things. For one, it may reverse the catabolic state by sparing skeletal muscle L-glutamine. It also may inhibit translocation of Gram-negative bacteria from the large intestine. L-glutamine helps maintain secretory IgA, which functions primarily by preventing the attachment of bacteria to mucosal cells.
L-glutamine appears to be required to support the proliferation of mitogen-stimulated lymphocytes, as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). It is also required for the maintenance of lymphokine-activated killer cells (LAK). L-glutamine can enhance phagocytosis by neutrophils and monocytes. It can lead to an increased synthesis of glutathione in the intestine, which may also play a role in maintaining the integrity of the intestinal mucosa by ameliorating oxidative stress.
The exact mechanism of the possible immunomodulatory action of supplemental L-glutamine, however, remains unclear. It is conceivable that the major effect of L-glutamine occurs at the level of the intestine. Perhaps enteral L-glutamine acts directly on intestine-associated lymphoid tissue and stimulates overall immune function by that mechanism, without passing beyond the splanchnic bed.
The anticatabolic/anabolic activity of supplemental L-glutamine can be explained by its effect in sparing skeletal muscle L-glutamine stores.
PHARMACOKINETICS
Following ingestion, L-glutamine is absorbed from the lumen of the small intestine into the enterocytes. Absorption is efficient and occurs by an active transport mechanism. Some metabolism of the amino acid takes place in the enterocytes. L-glutamine that is not metabolized in the enterocytes enters the portal circulation from whence it is transported to the liver, where again some portion of the amino acid is metabolized. L-glutamine not metabolized in the liver enters the systemic circulation, where it is distributed to the various tissues of the body. L-glutamine participates in various metabolic activities, including the formation of L-glutamate catalyzed by the enzyme glutaminase. It also participates in the synthesis of proteins, glutathione, pyrimidine and purine nucleotides and amino sugars. The transport of L-glutamine into cells is via an active process. L-glutamine is eliminated by glomerular filtration and is almost completely reabsorbed by the renal tables.
INDICATIONS AND USAGE
Glutamine has been shown to be beneficial when administered in the form of glutamine peptides via TPN in some patients with varying forms of catabolic stress, e.g., some cancer, transplantation, intensive-care, surgical and immune-suppressed patients. Benefits from enteral glutamine supplementation are generally less pronounced, but preliminary significant results have been reported with the use of oral glutamine in very-low-birth-weight infants and in some major trauma patients in whom glutamine seems to strengthen immunity, particularly in the gastrointestinal tract. Glutamine may help protect against some of the side effects of cancer chemotherapy and radiotherapy.
There is little concurring evidence that glutamine is an effective ergogenic aid, but there is some suggestion that it might help protect against exercise-induced immune impairment. Some dated research suggesting that glutamine might help curb alcohol craving has not been followed up. Claims that it helps prevent neurodegenerative disorders or that it modulates mood have not been substantiated.
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