Arginine

Arginine

Names
Other names 2-Amino-5-guanidinopentanoic acid
Identifiers
CAS Number	7200-25-1 N 157-06-2 R N 74-79-3 S N
3DMet	B01331
Beilstein Reference	1725411, 1725412 R, 1725413 S
ChEBI	CHEBI:29016 Y
ChEMBL	ChEMBL212301 N ChEMBL1485 N
ChemSpider	227 Y 64224 R N 6082 S N
DrugBank	DB00125 N
EC Number	230-571-3
Gmelin Reference	364938 R
IUPHAR/BPS	721
Jmol interactive 3D	Image Image
KEGG	C02385 N
MeSH	Arginine
PubChem	232 71070 R 6322 S
RTECS number	CF1934200 S
UNII	94ZLA3W45F Y
InChI InChI=1S/C6H14N4O2/c7-4(5(11)12)2-1-3-10-6(8)9/h4H,1-3,7H2,(H,11,12)(H4,8,9,10) Y Key: ODKSFYDXXFIFQN-UHFFFAOYSA-N Y
SMILES NC(CCCNC(N)=N)C(O)=O NC(CCC[nH]:c(:[nH]):[nH2])c(:[o]):[oH]
Properties
Chemical formula	C6H14N4O2
Molar mass	174.20 g·mol−1
Appearance	White crystals
Odor	Odourless
Melting point	260 °C; 500 °F; 533 K
Boiling point	368 °C (694 °F; 641 K)
Solubility in water	14.87 g/100 mL (20 °C)
Solubility	slightly soluble in ethanol insoluble in ethyl ether
log P	−1.652
Acidity (pKa)	12.488
Basicity (pKb)	1.509
Thermochemistry
Specific heat capacity (C)	232.8 J K−1 mol−1 (at 23.7 °C)
Std molar entropy (So298)	250.6 J K−1 mol−1
Std enthalpy of formation (ΔfHo298)	−624.9–−622.3 kJ mol−1
Std enthalpy of combustion (ΔcHo298)	−3.7396–−3.7370 MJ mol−1
Pharmacology
ATC code	B05XB01 S
Hazards
Safety data sheet	See: data page Sigma-Aldrich
GHS pictograms
GHS signal word	WARNING
GHS hazard statements	H319
GHS precautionary statements	P305+351+338
EU classification (DSD)	Xi
R-phrases	R36
S-phrases	S26
Lethal dose or concentration (LD, LC):
LD50 (Median dose)	5110 mg/kg (rat, oral)
Related compounds
Related alkanoic acids	N-Methyl-D-aspartic acid beta-Methylamino-L-alanine Guanidinopropionic acid Theanine Pantothenic acid
Related compounds	Panthenol
Supplementary data page
Structure and properties	Refractive index (n), Dielectric constant (εr), etc.
Thermodynamic data	Phase behaviour solid–liquid–gas
Spectral data	UV, IR, NMR, MS
N verify (what is YN ?)
Infobox references

Arginine (abbreviated as Arg or R) encoded by the codons CGU, CGC, CGA, CGG, AGA, and AGG ^[1] is an ɑ-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated -+NH3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated –COO- form under biological conditions), and a side chain of a 3-carbon aliphatic straight chain capped by a complex guanidinium, classifying it as a charged (at physiological pH), aliphatic amino acid. Arginine is classified as a semiessential or conditionally essential amino acid, depending on the developmental stage and health status of the individual.^[2] Preterm infants are unable to synthesize or create arginine internally, making the amino acid nutritionally essential for them.^[3] Most healthy people do not need to supplement with arginine because their body produces sufficient amounts.^[4]

Arginine was first isolated from a lupin seedling extract in 1886 by the German chemist Ernst Schultze.^[5]

Sources

Dietary sources

Arginine is a conditionally essential amino acid, meaning that whether or not it is required to be healthy is conditional on the health status or life cycle of the individual. 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 (e.g., cottage cheese, ricotta, milk, yogurt, whey protein drinks), beef, pork (e.g., bacon, ham), gelatin, poultry (e.g. chicken and turkey light meat), wild game (e.g. pheasant, quail), seafood (e.g., halibut, lobster, salmon, shrimp, snails, tuna)

• Plant sources

wheat germ and flour, lupins, buckwheat, granola, oatmeal, peanuts, nuts (coconut, pecans, cashews, walnuts, almonds, Brazil nuts, hazelnuts, pinenuts), seeds (pumpkin, sesame, sunflower), chickpeas, cooked soybeans, Phalaris canariensis (canaryseed or alpiste)

Biosynthesis

Arginine is synthesized from citrulline in arginine and proline metabolism by the sequential action of the cytosolic enzymes argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL). In terms of energy, this is costly, as the synthesis of each molecule of argininosuccinate requires hydrolysis of adenosine triphosphate (ATP) to adenosine monophosphate (AMP), 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 (NOS)
• from ornithine via catabolism of proline or glutamine/glutamate
• from asymmetric dimethylarginine (ADMA) 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.^[6]

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.^[2][7][8]

The roles of arginine include:

• Precursor for the synthesis of nitric oxide (NO)^[9] 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 (particularly bone)^[7][8]
• Quickens repair time of damaged tissue^[7][8]
• Helps decrease blood pressure in clinical hypertensive subjects^[10][11][12] 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 (NO), urea, ornithine, and agmatine; is necessary for the synthesis of creatine; and can also be used for the synthesis of polyamines (mainly through ornithine and to a lesser degree through agmatine), citrulline, and glutamate. As a precursor of nitric oxide, arginine may have a role in the treatment of some conditions where vasodilation is required.^[2] The presence of asymmetric dimethylarginine (ADMA), 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 (8%) in dental products (e.g., toothpaste) 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.^[13]

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.^[14]

Safety

L-arginine is generally recognized as safe (GRAS-status) at intakes of up to 20 g/d.^[15] Patients that have suffered from a heart attack should be stable prior to supplementation or administration of L-arginine. Concerns about the use of L-arginine by these patients are unfounded and efficacy as well as safety have been confirmed in a controlled clinical trial that refuted previous obsolete findings from the failed clinical VINTAGE MI study.^[16]

Structure

Delocalization of charge in guanidinium group of L-Arginine

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 pK_a 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.

Research

Growth hormone

Intravenously-administered arginine stimulates the secretion of growth hormone,^[17] and is used in growth hormone stimulation tests.^[18] Two studies have found that oral arginine supplementation is also effective at increasing resting GH levels. The first study found that oral preparations of arginine are effective at increasing growth hormone levels. In fact, the 9-gram dose resulted in mean peak GH levels of 6.4 (+/- 1.3) µg/L versus placebo levels of 2.9 (+/- 0.7).^[19] Another study found similar results. It included resting versus exercise and oral L-arginine versus oral placebo. The authors concluded that "Oral arginine alone (7 g) 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.^[20] 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.^[21]

MELAS syndrome

Several trials delved into effects of L-arginine in MELAS syndrome, a mitochondrial disease.^[22]

High blood pressure

Intravenous infusion of arginine reduces blood pressure in patients with hypertension as well as normal subjects.^[23]

A meta-analysis showed that L-arginine reduces blood pressure with pooled estimates of 5.4/2.7 mmHg for SBP/DBP.^[12]

Supplementation with L-arginine reduces diastolic blood pressure and lengthens pregnancy for women with gestational hypertension, including women with high blood pressure as part of pre-eclampsia.^[24] It does not lower systolic blood pressure or improve the baby's weight at birth.

See also

• Arginine glutamate
• AAKG
• Canavanine and canaline are toxic analogs of arginine and ornithine.

References

External links

Wikimedia Commons has media related to arginine.

• NIST Chemistry Webbook
• Mayo Clinic discussion of Arginine.
• National Institute of Health discussion of Arginine.

The encoded amino acid General topics Protein Peptide Genetic code By properties Aliphatic Branched-chain amino acids (Valine Isoleucine Leucine) Methionine Alanine Proline Glycine Aromatic Phenylalanine Tyrosine Tryptophan Histidine Polar, uncharged Asparagine Glutamine Serine Threonine Positive charge (pKa) Lysine (≈10.8) Arginine (≈12.5) Histidine (≈6.1) Negative charge (pKa) Aspartic acid (≈3.9) Glutamic acid (≈4.1) Cysteine (≈8.3) Tyrosine (≈10.1) Other classifications Essential amino acid Ketogenic amino acid Glucogenic amino acid Non-proteinogenic amino acid