Glutamine is the most abundant amino acid in muscle and plasma. It is used primarily as a fuel source by cells of the small intestine and cells of the immune system (lymphocytes and macrophages). Glutamine affects lymphocyte proliferation (reproduction/multiplication) and macrophage function, both of which are required for optimal immune response against foreign substances (antigens) such as bacteria, viruses or tumor cells. The liver and brain also utilize glutamine, but to a lesser extent, and the kidneys use glutamine only in times when ammonia production is necessary. About 40% of the glutamine used by the body is used by the gastrointestinal tract. This glutamine is made available primarily through the digestion of dietary protein. Practically all of the glutamine absorbed by the intestinal cells is metabolized by the intestinal cells. Therefore, circulating glutamine (in the blood) must be supplied by tissues that have the ability to produce glutamine, namely the liver and muscle.
Since muscle is the dominant supplier, and because muscle provides a store of glutamine, plasma glutamine becomes the link between skeletal muscle and the immune system. At any given time, lymphocytes and macrophages may be called upon to respond rapidly, effectively, and specifically to an immune challenge. This may require very high rates of fuel use, even in the resting state. If glutamine production by the muscle becomes impaired, then so does the immune system.
Glutamine is produced in muscle several ways: (1) Uptake of glutamate from the bloodstream accounts for 18-65% of glutamine production. (2) Breakdown of muscle protein produces glutamine directly, and it is this fact that leads to muscle catabolism if not sufficient glutamine is present when needed for immune function. (3) Breakdown of muscle protein also produces the branched chain amino acids glutamate, aspartate, and asparagine that are used for the synthesis of glutamine. It has also been suggested that glutamine can be produced using the carbon skeletons of carbohydrates, such as muscle glycogen and blood glucose.
"Extra" glutamine purportedly maintains skeletal muscle protein when the body's need for glutamine exceeds its natural production. A condition such as prolonged, exhaustive exercise may cause the activity of the immune response cells to be suppressed. During such periods of metabolic stress, increasing the amount of glutamine made available would increase protein synthesis, maintain glutamine production, and thereby maintain the activity of the immune response cells. If glutamine is not available, muscle catabolism (degradation/breakdown) proceeds and reductions in plasma glutamine concentration are likely, leaving the body's immune system more susceptible to invasion. Glutamine is therefore labeled by some as a "conditionally essential" amino acid.
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