Arginine
Skeletal formula of arginine
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Names | |||
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IUPAC names
Arginine
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Other names
2-Amino-5-guanidinopentanoic acid
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Identifiers | |||
3D model (
JSmol ) |
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3DMet |
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1725411, 1725412 D, 1725413 L | |||
ChEBI |
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ChEMBL |
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ChemSpider | |||
DrugBank |
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ECHA InfoCard
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100.000.738 | ||
EC Number |
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364938 D | |||
IUPHAR/BPS |
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KEGG |
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MeSH | Arginine | ||
PubChem CID
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RTECS number
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UNII |
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CompTox Dashboard (EPA)
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Properties | |||
C6H14N4O2 | |||
Molar mass | 174.204 g·mol−1 | ||
Appearance | White crystals | ||
Odor | Odourless | ||
Melting point | 260 °C; 500 °F; 533 K | ||
Boiling point | 368 °C (694 °F; 641 K) | ||
14.87 g/100 mL (20 °C) | |||
Solubility | slightly soluble in ethyl ether
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log P | −1.652 | ||
Acidity (pKa) | 2.18 (carboxyl), 9.09 (amino), 13.8 (guanidino) | ||
Thermochemistry | |||
Heat capacity (C)
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232.8 J K−1 mol−1 (at 23.7 °C) | ||
Std molar
entropy (S⦵298) |
250.6 J K−1 mol−1 | ||
Std enthalpy of (ΔfH⦵298)formation |
−624.9–−622.3 kJ mol−1 | ||
Std enthalpy of (ΔcH⦵298)combustion |
−3.7396–−3.7370 MJ mol−1 | ||
Pharmacology | |||
B05XB01 (WHO) S | |||
Hazards | |||
GHS labelling: | |||
Warning | |||
H319 | |||
P305+P351+P338 | |||
Lethal dose or concentration (LD, LC): | |||
LD50 (median dose)
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5110 mg/kg (rat, oral) | ||
Safety data sheet (SDS) | L-Arginine | ||
Related compounds | |||
Related alkanoic acids
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Related compounds
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Supplementary data page | |||
Arginine (data page) | |||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Arginine is the
The one-letter symbol R was assigned to arginine for its phonetic similarity.[4]
History
Arginine was first isolated in 1886 from
Sources
Production
It is traditionally obtained by hydrolysis of various cheap sources of protein, such as gelatin.[12] It is obtained commercially by fermentation. In this way, 25-35 g/liter can be produced, using glucose as a carbon source.[13]
Dietary sources
Arginine is classified as a semiessential or conditionally essential amino acid, depending on the developmental stage and health status of the individual.[14] Preterm infants are unable to synthesize arginine internally, making the amino acid nutritionally essential for them.[15] Most healthy people do not need to supplement with arginine because it is a component of all protein-containing foods[16] and can be synthesized in the body from glutamine via citrulline.[17][18] Additional, dietary arginine is necessary for otherwise healthy individuals temporarily under physiological stress, for example during recovery from burns, injury or sepsis,[18] or if either of the major sites of arginine biosynthesis, the small intestine and kidneys, have reduced function, because the small bowel does the first step of the synthesizing process and the kidneys do the second.[3]
Arginine is an essential amino acid for birds, as they do not have a urea cycle.[19] For some carnivores, for example cats, dogs[20] and ferrets, arginine is essential,[3] because after a meal, their highly efficient protein catabolism produces large quantities of ammonia which need to be processed through the urea cycle, and if not enough arginine is present, the resulting ammonia toxicity can be lethal.[21] This is not a problem in practice, because meat contains sufficient arginine to avoid this situation.[21]
Animal sources of arginine include meat, dairy products, and eggs,[22][23] and plant sources include seeds of all types, for example grains, beans, and nuts.[23]
Biosynthesis
Arginine is synthesized from
The pathways linking arginine, glutamine, and proline are bidirectional. Thus, the net use or production of these amino acids is highly dependent on cell type and developmental stage.
Arginine is made by the body as follows. The
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 increase the production of inducible nitric oxide synthase (NOS). This allows citrulline, a byproduct of the NOS-catalyzed production of nitric oxide, to be recycled to arginine in a pathway known as the citrulline to nitric oxide (citrulline-NO) or arginine-citrulline pathway. This is demonstrated by the fact that, in many cell types, nitric oxide synthesis can be supported to some extent by citrulline, and not just by arginine. This recycling is not quantitative, however, because citrulline accumulates in nitric oxide producing cells along with nitrate and nitrite, the stable end-products of nitric oxide breakdown.[24]
Function
Arginine plays an important role in
Proteins
Arginine's side chain is amphipathic, because at physiological pH it contains a positively charged guanidinium group, which is highly polar, at the end of a hydrophobic aliphatic hydrocarbon chain. Because globular proteins have hydrophobic interiors and hydrophilic surfaces,[33] arginine is typically found on the outside of the protein, where the hydrophilic head group can interact with the polar environment, for example taking part in hydrogen bonding and salt bridges.[34] For this reason, it is frequently found at the interface between two proteins.[35] The aliphatic part of the side chain sometimes remains below the surface of the protein.[34]
Arginine residues in proteins can be deiminated by PAD enzymes to form citrulline, in a post-translational modification process called citrullination.This is important in fetal development, is part of the normal immune process, as well as the control of gene expression, but is also significant in autoimmune diseases.[36] Another post-translational modification of arginine involves methylation by protein methyltransferases.[37]
Precursor
Arginine is the immediate precursor of nitric oxide, an important signaling molecule which can act as a second messenger, as well as an intercellular messenger which regulates vasodilation, and also has functions in the immune system's reaction to infection.
Arginine is also a precursor for 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). 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.[38]
Structure
The
Research
Growth hormone
Intravenously administered arginine is used in growth hormone stimulation tests[40] because it stimulates the secretion of growth hormone.[41] A review of clinical trials concluded that oral arginine increases growth hormone, but decreases growth hormone secretion, which is normally associated with exercising.[42] However, a more recent trial reported that although oral arginine increased plasma levels of L-arginine it did not cause an increase in growth hormone.[43]
Herpes-Simplex Virus (Cold sores)
Research from 1964 into amino acid requirements of herpes simplex virus in human cells indicated that "...the lack of arginine or histidine, and possibly the presence of lysine, would interfere markedly with virus synthesis", but concludes that "no ready explanation is available for any of these observations".[44]
Further reviews conclude that "lysine's efficacy for
High blood pressure
A meta-analysis showed that L-arginine reduces blood pressure with pooled estimates of 5.4 mmHg for systolic blood pressure and 2.7 mmHg for diastolic blood pressure.[47]
Supplementation with l-arginine reduces
Schizophrenia
Both liquid chromatography and liquid chromatography/mass spectrometric assays have found that brain tissue of deceased people with schizophrenia shows altered arginine metabolism. Assays also confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between L-ornithine level and the duration of illness. Moreover, cluster analyses revealed that L-arginine and its main metabolites L-citrulline, L-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. Despite this, the biological basis of schizophrenia is still poorly understood, a number of factors, such as dopamine hyperfunction, glutamatergic hypofunction, GABAergic deficits, cholinergic system dysfunction, stress vulnerability and neurodevelopmental disruption, have been linked to the aetiology and/or pathophysiology of the disease.[49]
Raynaud's phenomenon
Oral L-arginine has been shown to reverse digital necrosis in Raynaud syndrome[50]
Safety and potential drug interactions
L-arginine is recognized as safe (GRAS-status) at intakes of up to 20 grams per day.[51] L-arginine is found in many foods, such as fish, poultry, and dairy products, and is used as a dietary supplement.[52] It may interact with various prescription drugs and herbal supplements.[52]
See also
- Arginine glutamate
- AAKG
- analogs of arginine and ornithine.
References
- ^ "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived from the original on 9 October 2008. Retrieved 5 March 2018.
- ^ IUPAC-IUBMB Joint Commission on Biochemical Nomenclature. "Nomenclature and Symbolism for Amino Acids and Peptides". Recommendations on Organic & Biochemical Nomenclature, Symbols & Terminology etc. Archived from the original on 29 May 2007. Retrieved 2007-05-17.
- ^ ISBN 978-0-08-052503-7.
- .
- ^ Apel F (July 2015). "Biographie von Ernst Schulze" (PDF). Archived from the original (PDF) on 17 November 2015. Retrieved 2017-11-06.
- ^ Schulze E, Steiger E (1887). "Ueber das Arginin" [On arginine]. Zeitschrift für Physiologische Chemie. 11 (1–2): 43–65.
- ^ "BIOETYMOLOGY: ORIGIN IN BIO-MEDICAL TERMS: arginine (Arg R)". Retrieved 25 July 2019.
- . The structure for arginine is presented on p. 2882.
- .
- ^ Cohen JB (1919). Organic Chemistry for Advanced Students, Part 3 (2nd ed.). New York, New York, USA: Longmans, Green & Co. p. 140.
- .
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- ^ "Drugs and Supplements Arginine". Mayo Clinic. Retrieved 15 January 2015.
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- ^ Griffiths & Unwin 2016, p. 275.
- ^ Griffiths & Unwin 2016, p. 176.
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- ^ MedlinePlus Encyclopedia: Growth hormone stimulation test
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- ^ a b "L-Arginine". MedlinePlus, US National Institutes of Health. 13 October 2021. Retrieved 2021-05-27.
Sources
- Griffiths JR, Unwin RD (2016). Analysis of Protein Post-Translational Modifications by Mass Spectrometry. John Wiley & Sons. ISBN 978-1-119-25088-3.