Arginine

Description

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

Arginine is required for proper elimination of urea from the body. This occurs through a critical metabolic cycle which detoxifies the body of nitrogen compounds manufactured in the liver or by intestinal bacteria action. Subtle impairments of the liver's function can often lead to subclinical symptoms of hyperammonemia, which is the condition of poor excretion of urea. Symptoms of hyperammonemia may include chronic fatigue, headache, irritability, occasional diarrhea or nausea, lack of concentration, mental confusion, and intolerance to various foods, particularly high-protein foods.

Recent studies suggest deficiencies of arginine can occur in infants and some adults because the rate of production is not sufficient to meet their needs. Lysine competes with arginine for its utilization; therefore, individuals on a lysine-supplemented diet may produce a block in arginine synthesis. Arginine is useful in some individuals as a supplement to help treat the symptoms of hyperammonemia if they have a block in the proper metabolism or synthesis of arginine in the liver. Arginine in dietary protein is important in establishing the quantity of cholesterol to be synthesized by the liver.

Arginine is also useful for enhancing the function of the thymus gland in animals. The thymus gland is important in the promotion of proper functioning of the immune system. Animals given supplemental doses of arginine were found to have enhanced thymus activity with increased white blood cell response to infection. Arginine has been used therapeutically to lower blood ammonia levels in individuals who have an inability to properly manufacture urea. It has also been used as a potential immune stimulant in individuals with suppressed immunity. Safe doses of arginine can range from 500 to 2000 mg per day.

Recommended Dietary Allowances

An RDA has not been established for arginine because it is a nonessential amino acid.

Food Sources

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

Method of Action

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 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 B6 (pyridoxine) for their activity.

It has also been found zinc is a very important trace element that activates the urea cycle, and oral zinc therapy has been used to treat patients 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 20g of urea per day. If this rate decreases, ammonia accumulates in the blood to toxic levels. Normally, blood ammonia is very low (0.5mg/l). Only two to three times this level is required to produce toxic symptoms, including memory loss, psychosis, tremors, and inability to concentrate.

It has recently been found there are a number of hereditary enzyme deficiencies affecting the urea cycle, producing hyperammonemia. Many of these conditions are non-lethal, 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 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 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. Urinary creatinine excretion for a given individual is constant from day to day, which the amount excreted apparently 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 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 effect muscle contraction.

Abstracts

References

Blackburn, G.L., Grant, J.P., Young, V.R., ed. Amino Acids Metabolism and Medical Applications.

Morris, J.G. & Rogers, Q.R. Ammonia Intoxication in the Near-Adult Cat as a Result of Dietary Deficiency of Arginine. Science, 199:431-2, 1978.

Munro, H.N. & Crim, M.C. The Proteins and Amino Acids. Modern Nutrition in Health and Disease, eds: R.S. Goodhart & M.E. Shils, 6 ed., Philadelphia: Lea and Febiger, 1980.

Stewart, P.M., Batshaw, M., Valle, D. & Walser, M. Effects of Arginine-Free Meals on Ureagenesis in Cats. Am J of Phys, 241:E310-E315, 1981.

Valle, D., Walser, M., Brusilow, S.W., & Kaiser-Kupfer, M. Gyrate Atrophy of the Choroid and Retina: Amino Acid Metabolism and Correction of Hyperornithinemia with an Arginine-Deficient Diet. Journal of Clinical Investigation, 65:371-8, 1980.

Young, V.R., Meguid, M., Meredith, D.E., & Bier, D.M. Recent Developments in Knowledge of Human Amino Acid Requirements. Nitrogen Metabolism in Man, eds: J.C. Waterlow & J.M.L. Stephen. London: Applied Science Pubs, 1981.