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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. |
