Arginine is an α-amino acid.
It was first isolated in 1886.
The L-form is one of the 20 most common natural amino acids.
At the level of molecular genetics, in the structure of the messenger ribonucleic acid
mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons
that code for arginine during protein synthesis.
In mammals, arginine is classified as a semiessential or conditionally essential amino acid, depending
on the developmental stage and health status of the individual.
Preterm infants are unable to synthesize or create arginine internally, making the amino
acid nutritionally essential for them.
There are some conditions that put an increased demand on the body for the synthesis of L-arginine,
including surgical or other trauma, sepsis and burns.
Arginine was first isolated from a lupin seedling extract in 1886 by the Swiss chemist Ernst
Schultze.
In general, most people do not need to take arginine supplements because the body usually
produces significant amounts in healthy individuals.
Structure The amino acid side-chain of arginine consists
of a 3-carbon aliphatic straight chain, the distal end of which is capped by a complex
guanidinium group.
With a pKa of 12.48, the guanidinium group is positively charged in neutral, acidic,
and even most basic environments, and thus imparts basic chemical properties to arginine.
Because of the conjugation between the double bond and the nitrogen lone pairs, the positive
charge is delocalized, enabling the formation of multiple H-bonds.
Sources Dietary sources
Arginine is a conditionally nonessential amino acid, meaning that most of the time it can
be manufactured by the human body, and does not need to be obtained directly through the
diet.
The biosynthetic pathway, however, does not produce sufficient arginine, and some must
still be consumed through diet.
Individuals with poor nutrition or certain physical conditions may be advised to increase
their intake of foods containing arginine.
Arginine is found in a wide variety of foods, including:
Animal sources dairy products, beef, pork, gelatin , poultry,
wild game, seafood Plant sources
wheat germ and flour, lupins, buckwheat, granola, oatmeal, peanuts, nuts, seeds, chickpeas,
cooked soybeans, Phalaris canariensis Biosynthesis
Arginine is synthesized from citrulline by the sequential action of the cytosolic enzymes
argininosuccinate synthetase and argininosuccinate lyase.
In terms of energy, this is costly, as the synthesis of each molecule of argininosuccinate
requires hydrolysis of adenosine triphosphate to adenosine monophosphate, i.e., two ATP
equivalents.
In essence, taking an excess of arginine gives more energy by saving ATPs that can be used
elsewhere.
Citrulline can be derived from multiple sources: from arginine via nitric oxide synthase
from ornithine via catabolism of proline or glutamine/glutamate
from asymmetric dimethylarginine via DDAH The pathways linking arginine, glutamine,
and proline are bidirectional.
Thus, the net utilization or production of these amino acids is highly dependent on cell
type and developmental stage.
On a whole-body basis, synthesis of arginine occurs principally via the intestinal–renal
axis, wherein epithelial cells of the small intestine, which produce citrulline primarily
from glutamine and glutamate, collaborate with the proximal tubule cells of the kidney,
which extract citrulline from the circulation and convert it to arginine, which is returned
to the circulation.
As a consequence, impairment of small bowel or renal function can reduce endogenous arginine
synthesis, thereby increasing the dietary requirement.
Synthesis of arginine from citrulline also occurs at a low level in many other cells,
and cellular capacity for arginine synthesis can be markedly increased under circumstances
that also induce iNOS.
Thus, citrulline, a coproduct of the NOS-catalyzed reaction, can be recycled to arginine in a
pathway known as the citrulline-NO or arginine-citrulline pathway.
This is demonstrated by the fact that, in many cell types, citrulline can substitute
for arginine to some degree in supporting NO synthesis.
However, recycling is not quantitative because citrulline accumulates along with nitrate
and nitrite, the stable end-products of NO, in NO-producing cells.
Function Arginine plays an important role in cell division,
the healing of wounds, removing ammonia from the body, immune function, and the release
of hormones.
The benefits and functions attributed to oral supplementation of L-arginine include:
Precursor for the synthesis of nitric oxide Non-L-arginine derived NO can be generated
by the nitrate-nitrite-nitric oxide pathway that is monitored through saliva testing.
Reduces healing time of injuries Quickens repair time of damaged tissue
Helps decrease blood pressure in clinical hypertensive subjects NO-mediated decrease
in blood pressure is influenced by both the L-arginine-dependent nitric oxide synthase
pathway and non-L-arginine or alternative pathway through nitrate-rich foods such as
beets and spinach.
Proteins The distributing basics of the moderate structure
found in geometry, charge distribution, and ability to form multiple H-bonds make arginine
ideal for binding negatively charged groups.
For this reason, arginine prefers to be on the outside of the proteins, where it can
interact with the polar environment.
Incorporated in proteins, arginine can also be converted to citrulline by PAD enzymes.
In addition, arginine can be methylated by protein methyltransferases.
Precursor Arginine is the immediate precursor of nitric
oxide, urea, ornithine, and agmatine; is necessary for the synthesis of creatine; and can also
be used for the synthesis of polyamines, citrulline, and glutamate.
As a precursor of nitric oxide, arginine may have a role in the treatment of some conditions
where vasodilation is required.
The presence of asymmetric dimethylarginine, a close relative, inhibits the nitric oxide
reaction; therefore, ADMA is considered a marker for vascular disease, just as L-arginine
is considered a sign of a healthy endothelium.
Treatment of dentin hypersensitivity Arginine in dental products provides effective
relief from sensitive teeth by depositing a dentin-like mineral, containing calcium
and phosphate, within the dentin tubules and in a protective layer on the dentin surface.
Treatment of herpes simplex virus An unproven claim is that a low ratio of arginine
to lysine may be of benefit in the treatment of herpes simplex virus.
For more information, refer to Herpes - Treatment also see journal article.
Possible increased risk of death after supplementation following heart attack
A clinical trial found that patients taking an L-arginine supplement following a heart
attack found no change in the heart's vascular tone or decrease in the symptoms of congestive
heart failure.
In fact, six more patients that were taking L-arginine died than those taking a placebo,
resulting in early termination of the study with the recommendation that the supplement
not be used by heart attack patients.
These findings suggest L-arginine is not beneficial post-heart-attack.
Potential medical uses Lung inflammation and asthma
Inhalation of L-arginine can increase lung inflammation and worsen asthma.
Growth hormone Intravenously-administered arginine stimulates
the secretion of growth hormone, and is used in growth hormone stimulation tests.
Two studies have found that oral L-arginine supplementation is also effective at increasing
resting GH levels.
The first study found that oral preparations of L-arginine are effective at increasing
growth hormone levels.
In fact, the 9-gram dose resulted in mean peak GH levels of 6.4 microg/L versus placebo
levels of 2.9.
Another study found similar results.
It included resting versus exercise and oral L-arginine versus oral placebo.
The authors concluded that "Oral arginine alone stimulated GH release, but a greater
GH response was seen with exercise alone.
The combined effect of arginine before exercise attenuates the GH response...
GH production: Ex > Arg+Ex > Arg > placebo" suggesting against supplementing with arginine
alone prior to exercise if the goal is to raise GH levels, but concurring with the previous
study that oral L-arginine increases GH on days free of significant exercise.
In contrast to these two studies that found increased resting GH due to oral arginine
supplementation, a third study did not find increase in resting GH levels from oral supplementation.
In that study, oral preparations of L-arginine were ineffective at increasing growth hormone
levels despite being effective at increasing plasma levels of L-arginine.
MELAS syndrome Several trials delved into effects of L-arginine
in MELAS syndrome, a mitochondrial disease.
Sepsis Cellular arginine biosynthetic capacity determined
by activity of argininosuccinate synthetase is induced by the same mediators of septic
response — endotoxin and cytokines — that induce nitric oxide synthase, the enzyme responsible
for nitric oxide synthesis.
Malate salt The malate salt of arginine can also be used
during the treatment of alcoholic hepatitis and advanced cirrhosis.
Pre-eclampsia A preliminary study of supplementation with
L-arginine and antioxidant vitamins showed that this combination may help to combat abnormally
high blood pressure during high-risk pregnancies.
Hypertension Intravenous infusion of arginine reduces blood
pressure in patients with hypertension as well as normal subjects.
A recent meta-analysis showed that L-arginine reduces blood pressure with pooled estimates
of 5.4/2.7 mmHg for SBP/DBP.
Erectile dysfunction Arginine taken in combination with proanthocyanidins
or glutamic acid and yohimbine, has also been used as a treatment for erectile dysfunction.
Anxiety Dietary supplementation of L-arginine taken
in combination with L-lysine has been shown potentially useful in treating people subjected
to high levels of mental stress and anxiety, in a double-blind, placebo controlled and
randomized study, involving 108 Japanese adults.
Trait anxiety and state anxiety induced by cognitive stress battery was significantly
reduced, and basal levels of the stress hormone cortisol were decreased.
The study was funded by Ajinomoto, Co. Inc., an industrial manufacturer of lysine and arginine.
See also Arginine glutamate
AAKG Canavanine and canaline are toxic analogs
of arginine and ornithine.
References
External links NIST Chemistry Webbook
Mayo Clinic discussion of Arginine.
National Institute of Health discussion of Arginine.