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Citrulline

Description

Citrulline is a nonessential amino acid, which means that it is manufactured from other amino acids in the liver; it does not have to be obtained directly through the diet.

Citrulline is a precursor to arginine and is involved in the formation of urea in the liver. The synthesis and elimination of urea is essential for removing toxic nitrogen metabolites from the body. These metabolites build up from the digestion, absorption, and metabolism of protein. Citrulline works along with aspartic acid, citric acid, and magnesium in helping to improve nitrogen metabolite excretion.

Studies suggest that deficiencies may occur in some infants and adults because the rate of production may not be equal to their need.

No therapeutic application of citrulline has been identified. Some individuals possess a genetic defect which prevents proper conversion of citrulline to arginine. This results in the buildup of citrulline in the blood and a deficiency of arginine. This condition is associated with ammonia build up in the body and symptoms such as irritability and mental confusion. Zinc and vitamin B-6. are useful for promoting the conversion of citrulline to arginine.

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Method of Action

Citrulline is a precursor of arginine. Arginine is a contributing member of the various amino acids found in the urea cycle, which is responsible for detoxifying ammonia. Ammonia is a by-product of bacterial metabolism in the intestinal tract and must be detoxified in the liver. The urea cycle is also responsible for eliminating other catabolic sources of nitrogen so the body does not build up toxic nitrogen metabolites. In 1932, H.A. Krebs and K.Z. Henseleit noted that liver slices were capable of forming urea by a cyclic process in which the amino acid ornithine was first converted to citrulline and then to arginine. The ultimate cleavage of arginine produces urea and regenerates ornithine. This cycle is dependent upon enzymes called transaminases, which require vitamin B-6. (pyridoxine) for their activity. It has also been found that zinc is a very important trace element that activates the urea cycle, and oral zinc therapy has been used to treat patients that are suffering from hyperammonemia. The urea cycle is also dependent upon the proper conversion of glutamate to glutamine. These amino acids have been used in therapy to facilitate more rapid elimination of ammonia. Human adults excrete approximately 20 grams of urea per day. If this rate decreases, ammonia accumulates in the blood to toxic levels. Normally, blood ammonia is very low (0.5 mg/l). Only two to three times this level is required to produce toxic symptoms, including memory loss, psychosis, tremors, and ability to concentrate.

It has recently been found that there are a number of hereditary enzyme deficiencies that affect the urea cycle, producing hyperammonemia. Many of these conditions are nonlethal, but are associated with psychiatric complications. Over twenty different types of these problems have been observed. A common feature of all these defects of the urea cycle is an intolerance to high-protein diets and the relationship of mental symptoms to elevated protein in the diet. Toxic accumulation of ammonia in the blood is also seen in alcoholic liver disease and may account for some of the delirium tremen symptoms. It has also been found that ammonia can accumulate in the blood as a consequence of intestinal stasis and a "toxic bowel" reaction. In all of these cases a lower-protein diet; selected supplementation with arginine, ornithine, or citrulline; or supplementation with zinc, vitamin B-6, or vitamin B-6, or vitamin C may be desirable.

Arginine is also the precursor to the polyamines such as cadaverine, putrecine, spermine, and spermidine. These polyamines help stabilize DNA. Arginine is also the precursor to creatine, which is ultimately converted to creatinine. This is a compound of special importance in muscle. Creatine phosphate serves as an energy buffer for muscular contraction. The urinary creatinine excretion for a given individual is extremely constant from day to day, with the amount excreted being directly related to the muscle mass of the person. Individuals who are undergoing muscle wasting have increased creatinine spill in their urine. The urea cycle enzymes are also closely related to the transsulfuration pathway involving S-adenosyl methionine. This pathway is dependent upon adequate dietary intake of the essential amino acid methionine. Insufficiencies of the sulfur amino acids can, therefore, have an adverse impact upon the proper metabolism of arginine and ornithine to creatinine, and may adversely affect muscle contraction.

Food Sources

Citrulline is a nonessential amino acid, which means that it is manufactured from other amino acids in the liver; it does not have to be obtained directly through the diet.

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