When the human body is altered by factors such as stress or disease, its demands for extra glutamine can change drastically. One form of stress that occurs is when a person bodybuilds using heavy poundages and intense training. During this training the use of glutamine by the other organs of the body increases in response to bodily stress. Intense exercise also causes the production of lactic acid and ammonium by the muscles. As a result, the many tissues that need glutamine, but can’t produce it, are provided with ample supplies during the exercise induced stress. The problem is that the muscles are having their intracellular stores depleted in the process. Intense exercise also causes the release of catabolic hormones such as corticosteroids. These also contribute to the depletion of muscle glutamine stores by increasing the release of glutamine from muscle cells. The result is that muscles become severely glutamine depleted.

The amount of water in cells can change in a matter of minutes, going from being fully hydrated to a state of dehydration. It has been found that the amount of water inside a muscle cell can alter its metabolism, especially protein synthesis and turnover. When cells are swollen with water, this inhibits the breakdown of protein, glycogen and glucose and stimulates protein and glycogen synthesis. If a cell becomes dehydrated, it shrinks and goes into a catabolic state that breaks down the muscle’s vital proteins.

When glutamine levels are high in muscle cells, this stimulates the entry of other amino acids into the cell. Amino acids cannot directly enter the cell, but must be carried in by a special transport system. The unique thing about this system is that when it allows an amino acid to enter, it also allows sodium to enter. As the amino and sodium levels increase in the cell, this causes water to be absorbed across the membrane and the cell swells to an anabolic state. When glutamine levels are depleted during intense exercise the cells become dehydrated and enter a catabolic state.

When a person trains intensely they will start depleting their muscle glutamine stores before they have fully recovered from their previous workout. The result is that each day the amount of muscle glutamine gets a little lower. The more a person trains, the more glutamine they use and the greater the catabolic response. People suffering from overtraining are also more susceptible to disease and infection as a result of lowered immunity. This may be due to the role of glutamine as a primary source of fuel for the immune system.

An Amino Acid With Many Functions. Sir Hans Krebs, a pioneer in glutamine research, stated once that "most amino acids have multiple functions, but glutamine appears to be the most versatile."

Glutamine is the most abundant amino acid found in blood, and is a vehicle for nitrogen transport. It is formed in the body when glutamic acid binds to ammonia. This reaction is catalyzed by the enzyme glutamine synthetase which is abundant in muscle, lung, and many other tissues. Glutamine-consuming tissues, such as the GI tract, the liver, and the immune system, use glutamine to make nucleotides, proteins, and amino sugars. Glutamine carries potentially toxic ammonia to the kidneys for excretion, and participates in maintaining normal acid-base balance by providing the ammonia that is necessary to counterbalance acidic compounds. During metabolic acidosis, the kidneys can siphon off large amounts of glutamine.

The liver assumes a central role in regulating glutamine metabolism for all other organs in the body. The liver synthesizes extra glutamine when needed by other tissues, and breaks down glutamine when there is excess.

The Gut-Glutamine Connection. Rapidly replicating cells, such as intestinal mucosal cells, pancreatic cells, immune cells and endothelial cells, tend to be avid glutamine consumers. In fact, the human intestinal tract removes as much as 12-13% of the circulating blood glutamine in addition to the glutamine absorbed from dietary origin. Intestinal mucosal cells need glutamine as a nitrogen donor for the biosynthesis of a number of important compounds, including nucleotides needed for cell division, amino sugars for building the glycosaminoglycans of intestinal mucous, amino acids that are crucial for protein synthesis, as well as for an energy source. In fact, mucosal cells actually use more glutamine than glucose for energy production.

Stress Puts Glutamine in High Demand. During starvation, the liver and intestine cooperate in balancing glutamine needs. The gut uses the extra glutamine generated by the liver during starvation and converts it to alanine which is then used by the liver to form glucose. This mechanism provides energy for both organs and also helps prevent the loss of muscle during starvation.

In conditions of physical trauma, surgical stress, or inflammatory bowel disease, the intestinal tract uses very large amounts of glutamine and very little glucose for energy. This results in a fall of blood glutamine, and skeletal muscle is broken down to supply more glutamine. This is why trauma victims or surgery patients often lose substantial amounts of lean body mass.

Glutamine And Intestinal Immune Function. Most people are not aware that the GI tract is probably the most important part of their immune system. It constantly protects us from the harmful effects of ingested pathogenic bacteria.

The intestinal immune system has three lines of defense. First, immune cells interspersed within the mucosa help prevent pathogenic organisms from entering the circulatory system. Second are the mesenteric lymph nodes which are rich in immune cells. They intercept any pathogens that made it through the mucosa. The immune cells of the liver are the third line of defense which kicks in only in severe intestinal infections.

When the intestinal immune barrier is weakened, as in "leaky gut syndrome," pathogens may have to be intercepted at the mesenteric lymph nodes or the liver. In more severe cases, such as sepsis or endotoxemia, the liver's immune system is overwhelmed, and pathogens can enter the systemic circulation causing fever and other infectious disease symptoms.

The immune cells of mucosa, liver and mesentery depend on glutamine as a key nitrogen donor and energy source. During infections of intestinal origin, immune cells need more glutamine, and the liver's glutamine consumption can rise about ten-fold. Just as in trauma or surgery, intestinal infections can result in lower blood glutamine levels and muscle wasting.

Glutamine: A Conditionally-Essential Amino Acid. These and other observations have led scientists to suggest that glutamine is a conditionally essential amino acid, that is, it may have to be supplied by the diet to maintain normal gut, liver, immune and muscle function during critical illness and other physiological stress.

Many clinical studies support the fact that dietary glutamine is crucial in maintaining normal function of the entire gastrointestinal tract, including the liver and pancreas. Glutamine helps maintain normal intestinal permeability, mucosal cell regeneration and structure, especially during periods of physiological stress.

Glutamine is also importent for maintaining lean body (muscle) mass. It helps preserve normal muscle mass during conditions of physiological stress. In addition, glutamine is necessary to regulate protein synthesis.

How Much Glutamine Does it Take? A healthy intestinal tract is usually able to obtain adequate amounts of glutamine supplied by blood and dietary sources. Typical diets provide 3.5 to 7 grams of glutamine per day. More glutamine is often needed to maintain normal glutamine levels and gut function at times when the intestine is subjected to stress, such as from infections, trauma, inflammation, food allergy or other irritations. Under these conditions, an extra 10 to 40 grams of glutamine per day may be needed just to maintain normal intestinal structure and function.

Glutamine is virtually non-toxic even in very large quantities. It is rapidly metabolized and does not increase blood glutamine or ammonia above their normal levels.

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