Arginine 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.
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 that are 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
Deficiencies of a nonessential amino acid will not occur
if a well-balanced diet is consume because the intake of proper foods will
allow the body to produce exactly the amount of amino acid required to function
Recent studies suggest that 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 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
Arginine is also useful for enhancing the function of the
thymus gland in animals. The thymus gland is important in the promotion of
proper function 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.
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 inability 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 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 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 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 phosphates serves as an energy buffer for muscular contraction. The
urinary creatinine excretion for a given individual is extremely constant from
day to day, which the
amount excreted apparently being directly related to the muscle mass of the
Individuals who are undergoing muscle wasting have
increased creatine 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 effect muscle contraction.