Arginine

Last updated
Arginine
Arginin - Arginine.svg
Skeletal formula of arginine
Arginine-from-xtal-3D-bs-17.png
Arginine-from-xtal-3D-sf.png
Names
IUPAC names
Arginine
Other names
2-Amino-5-guanidinopentanoic acid
Identifiers
3D model (JSmol)
3DMet
1725411, 1725412 D, 1725413 L
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.738 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • L:230-571-3
364938 D
KEGG
MeSH Arginine
PubChem CID
RTECS number
  • L:CF1934200 L
UNII
  • 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)/t4-/m0/s1 Yes check.svgY
    Key: ODKSFYDXXFIFQN-BYPYZUCNSA-N Yes check.svgY
  • D/L:Key: ODKSFYDXXFIFQN-UHFFFAOYSA-N
  • D:Key: ODKSFYDXXFIFQN-SCSAIBSYSA-N
  • L:C(C[C@@H](C(=O)O)N)CNC(=N)N
  • D/L:C(CC(C(=O)O)N)CNC(=N)N
  • D:C(C[C@H](C(=O)O)N)CNC(=N)N
  • L HCl:[Cl-].NC(CCCNC(N)=[NH2+])C([O-])=O
  • L Zwitterion:NC(CCCNC(N)=[NH2+])C([O-])=O
Properties
C6H14N4O2
Molar mass 174.204 g·mol−1
AppearanceWhite 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 ethanol
insoluble in ethyl ether
log P −1.652
Acidity (pKa)2.18 (carboxyl), 9.09 (amino), 13.8 (guanidino)
Thermochemistry
232.8 J K−1 mol−1 (at 23.7 °C)
Std molar
entropy
(S298)
250.6 J K−1 mol−1
−624.9–−622.3 kJ mol−1
−3.7396–−3.7370 MJ mol−1
Pharmacology
B05XB01 ( WHO ) S
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H319
P305+P351+P338
Lethal dose or concentration (LD, LC):
5110 mg/kg (rat, oral)
Safety data sheet (SDS) L-Arginine
Related compounds
Related alkanoic acids
Related compounds
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).

Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2) and both the amino and guanidino groups are protonated, resulting in a cation. Only the l-arginine (symbol Arg or R) enantiomer is found naturally. [1] Arg residues are common components of proteins. It is encoded by the codons CGU, CGC, CGA, CGG, AGA, and AGG. [2] The guanidine group in arginine is the precursor for the biosynthesis of nitric oxide. [3] Like all amino acids, it is a white, water-soluble solid.

Contents

The one-letter symbol R was assigned to arginine for its phonetic similarity. [4]

History

Arginine was first isolated in 1886 from yellow lupin seedlings by the German chemist Ernst Schulze and his assistant Ernst Steiger. [5] [6] He named it from the Greek árgyros (ἄργυρος) meaning "silver" due to the silver-white appearance of arginine nitrate crystals. [7] In 1897, Schulze and Ernst Winterstein (1865–1949) determined the structure of arginine. [8] Schulze and Winterstein synthesized arginine from ornithine and cyanamide in 1899, [9] but some doubts about arginine's structure lingered [10] until Sørensen's synthesis of 1910. [11]

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 citrulline in the urea cycle by the sequential action of the cytosolic enzymes argininosuccinate synthetase and argininosuccinate lyase. This is an energetically costly process, because for each molecule of argininosuccinate that is synthesized, one molecule of adenosine triphosphate (ATP) is hydrolyzed to adenosine monophosphate (AMP), consuming two ATP equivalents.

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 biosynthesis. Arginine biosynthesis pathway.png
Arginine biosynthesis.

Arginine is made by the body as follows. The epithelial cells of the small intestine produce citrulline, primarily from glutamine and glutamate, which is secreted into the bloodstream which carries it to the proximal tubule cells of the kidney, which extract the citrulline and convert it to arginine, which is returned to the blood. This means that impaired small bowel or renal function can reduce arginine synthesis and thus create a dietary requirement for arginine. For such a person, arginine would become "essential".

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 cell division, wound healing, removing ammonia from the body, immune function, [25] and the release of hormones. [14] [26] [27] It is a precursor for the synthesis of nitric oxide (NO), [28] making it important in the regulation of blood pressure. [29] [30] Arginine is necessary for T-Cells to function in the body, and can lead to their deregulation if depleted. [31] [32]

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

Delocalization of charge in guanidinium group of
l-Arginine Betaine Arginine.png
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 guanidinium group, which has a pKa of 13.8, [39] and is therefore always protonated and positively charged at physiological pH. Because of the conjugation between the double bond and the nitrogen lone pairs, the positive charge is delocalized, enabling the formation of multiple hydrogen bonds.

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 herpes labialis may lie more in prevention than treatment." and that "the use of lysine for decreasing the severity or duration of outbreaks" is not supported, while further research is needed. [45] A 2017 study concludes that "clinicians could consider advising patients that there is a theoretical role of lysine supplementation in the prevention of herpes simplex sores but the research evidence is insufficient to back this. Patients with cardiovascular or gallbladder disease should be cautioned and warned of the theoretical risks." [46]

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 diastolic blood pressure and lengthens pregnancy for women with gestational hypertension, including women with high blood pressure as part of pre-eclampsia. It did not lower systolic blood pressure or improve weight at birth. [48]

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

Related Research Articles

<span class="mw-page-title-main">Amino acid</span> Organic compounds containing amine and carboxylic groups

Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 appear in the genetic code of life.

<span class="mw-page-title-main">Phenylalanine</span> Type of α-amino acid

Phenylalanine is an essential α-amino acid with the formula C
9
H
11
NO
2
. It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino acid is classified as neutral, and nonpolar because of the inert and hydrophobic nature of the benzyl side chain. The L-isomer is used to biochemically form proteins coded for by DNA. Phenylalanine is a precursor for tyrosine, the monoamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), and the biological pigment melanin. It is encoded by the codons UUU and UUC.

<span class="mw-page-title-main">Methionine</span> Sulfur-containing amino acid

Methionine is an essential amino acid in humans.

<span class="mw-page-title-main">Lysine</span> Amino acid

Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated −NH+
3
form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO form under biological conditions), and a side chain lysyl ((CH2)4NH2), classifying it as a basic, charged (at physiological pH), aliphatic amino acid. It is encoded by the codons AAA and AAG. Like almost all other amino acids, the α-carbon is chiral and lysine may refer to either enantiomer or a racemic mixture of both. For the purpose of this article, lysine will refer to the biologically active enantiomer L-lysine, where the α-carbon is in the S configuration.

<span class="mw-page-title-main">Glutamine</span> Chemical compound

Glutamine is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, polar amino acid. It is non-essential and conditionally essential in humans, meaning the body can usually synthesize sufficient amounts of it, but in some instances of stress, the body's demand for glutamine increases, and glutamine must be obtained from the diet. It is encoded by the codons CAA and CAG. It is named after glutamic acid, which in turn is named after its discovery in cereal proteins, gluten.

<span class="mw-page-title-main">Ornithine</span> Chemical compound

Ornithine is a non-proteinogenic α-amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl.

<span class="mw-page-title-main">Citrulline</span> Chemical compound

The organic compound citrulline is an α-amino acid. Its name is derived from citrullus, the Latin word for watermelon. Although named and described by gastroenterologists since the late 19th century, it was first isolated from watermelon in 1914 by Japanese researchers Yotaro Koga and Ryo Odake and further codified by Mitsunori Wada of Tokyo Imperial University in 1930. It has the formula H2NC(O)NH(CH2)3CH(NH2)CO2H. It is a key intermediate in the urea cycle, the pathway by which mammals excrete ammonia by converting it into urea. Citrulline is also produced as a byproduct of the enzymatic production of nitric oxide from the amino acid arginine, catalyzed by nitric oxide synthase.

An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life forms, the nine amino acids humans cannot synthesize are valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, threonine, histidine, and lysine.

Agmatine, also known as 4-aminobutyl-guanidine, was discovered in 1910 by Albrecht Kossel. It is a chemical substance which is naturally created from the amino acid arginine. Agmatine has been shown to exert modulatory action at multiple molecular targets, notably: neurotransmitter systems, ion channels, nitric oxide (NO) synthesis and polyamine metabolism and this provides bases for further research into potential applications.

<span class="mw-page-title-main">Nitric oxide synthase</span> Enzyme catalysing the formation of the gasotransmitter NO(nitric oxide)

Nitric oxide synthases (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and peristalsis, and is involved in angiogenesis and neural development. It may function as a retrograde neurotransmitter. Nitric oxide is mediated in mammals by the calcium-calmodulin controlled isoenzymes eNOS and nNOS. The inducible isoform, iNOS, involved in immune response, binds calmodulin at physiologically relevant concentrations, and produces NO as an immune defense mechanism, as NO is a free radical with an unpaired electron. It is the proximate cause of septic shock and may function in autoimmune disease.

<span class="mw-page-title-main">Mitochondrial matrix</span> Space within the inner membrane of the mitochondrion

In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.

<span class="mw-page-title-main">Lysinuric protein intolerance</span> Medical condition

Lysinuric protein intolerance (LPI) is an autosomal recessive metabolic disorder affecting amino acid transport.

<span class="mw-page-title-main">Argininosuccinate synthase</span> Enzyme

Argininosuccinate synthase or synthetase is an enzyme that catalyzes the synthesis of argininosuccinate from citrulline and aspartate. In humans, argininosuccinate synthase is encoded by the ASS gene located on chromosome 9.

<span class="mw-page-title-main">Cyanophycin</span>

Cyanophycin, also known as CGP or multi-L-arginyl-poly, is a non-protein, non-ribosomally produced amino acid polymer composed of an aspartic acid backbone and arginine side groups.

Arginine alpha-ketoglutarate (AAKG) is a salt of the amino acid arginine and alpha-ketoglutaric acid. It is marketed as a bodybuilding supplement.

<span class="mw-page-title-main">Glycocyamine</span> Chemical compound

Glycocyamine is a metabolite of glycine in which the amino group has been converted into a guanidine by guanylation. In vertebrate organism it is then transformed into creatine by methylation.

<span class="mw-page-title-main">Homoarginine</span> Chemical compound

Homoarginine is an nonproteinogenic alpha-amino acid. It is structurally equivalent to a one-methylene group-higher homolog of arginine and to the guanidino derivative of lysine. L-Homoarginine is the naturally-occurring enantiomer. Physiologically, homoarginine increases nitric oxide (NO) supply and betters endothelial functions in the body, with a particular correlation and effect towards cardiovascular outcome and mortality. At physiological pH, homoarginine is cationic: the guanidino group is protonated.

<span class="mw-page-title-main">Homocitrulline</span> Chemical compound

L-Homocitrulline is an amino acid and a metabolite of ornithine in mammalian metabolism. The amino acid can be detected in larger amounts in the urine of individuals with urea cycle disorders. At present, it is thought that the depletion of the ornithine supply causes the accumulation of carbamyl-phosphate in the urea cycle which may be responsible for the enhanced synthesis of homocitrulline and homoarginine. Both amino acids can be detected in urine. Amino acid analysis allows for the quantitative analysis of these amino acid metabolites in biological fluids such as urine or blood.

Arginine and proline metabolism is one of the central pathways for the biosynthesis of the amino acids arginine and proline from glutamate. The pathways linking arginine, glutamate, and proline are bidirectional. Thus, the net utilization or production of these amino acids is highly dependent on cell type and developmental stage. Altered proline metabolism has been linked to metastasis formation in breast cancer.

<span class="mw-page-title-main">Argpyrimidine</span> Chemical compound

Argpyrimidine is an organic compound with the chemical formula C11H18N4O3. It is an advanced glycation end-product formed from arginine and methylglyoxal through the Maillard reaction. Argpyrimidine has been studied for its food chemistry purposes and its potential involvement in aging diseases and Diabetes Mellius.

References

  1. "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.
  2. 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.
  3. 1 2 3 Ignarro LJ (2000-09-13). Nitric Oxide: Biology and Pathobiology. Academic Press. p. 189. ISBN   978-0-08-052503-7.
  4. "IUPAC-IUB Commission on Biochemical Nomenclature A One-Letter Notation for Amino Acid Sequences". Journal of Biological Chemistry. 243 (13): 3557–3559. 10 July 1968. doi:10.1016/S0021-9258(19)34176-6.
  5. Apel F (July 2015). "Biographie von Ernst Schulze" (PDF). Archived from the original (PDF) on 17 November 2015. Retrieved 2017-11-06.
  6. Schulze E, Steiger E (1887). "Ueber das Arginin" [On arginine]. Zeitschrift für Physiologische Chemie. 11 (1–2): 43–65.
  7. "BIOETYMOLOGY: ORIGIN IN BIO-MEDICAL TERMS: arginine (Arg R)" . Retrieved 25 July 2019.
  8. Schulze E, Winterstein E (September 1897). "Ueber ein Spaltungs-product des Arginins" [On a cleavage product of arginine]. Berichte der Deutschen Chemischen Gesellschaft (in German). 30 (3): 2879–2882. doi:10.1002/cber.18970300389. The structure for arginine is presented on p. 2882.
  9. Schulze E, Winterstein E (October 1899). "Ueber die Constitution des Arginins" [On the constitution of arginine]. Berichte der Deutschen Chemischen Gesellschaft (in German). 32 (3): 3191–3194. doi:10.1002/cber.18990320385.
  10. Cohen JB (1919). Organic Chemistry for Advanced Students, Part 3 (2nd ed.). New York, New York, USA: Longmans, Green & Co. p. 140.
  11. Sölrensen SP (January 1910). "Über die Synthese des dl-Arginins (α-Amino-δ-guanido-n-valeriansäure) und der isomeren α-Guanido-δ-amino-n-valeriansäure" [On the synthesis of racemic arginine (α-amino-δ-guanido-n-valeric acid) and of the isomeric α-guanido-δ-amino-n-valeric acid]. Berichte der Deutschen Chemischen Gesellschaft (in German). 43 (1): 643–651. doi:10.1002/cber.191004301109.
  12. Brand E, Sandberg M (1932). "d-Arginine Hydrochloride". Org. Synth. 12: 4. doi:10.15227/orgsyn.012.0004.
  13. Drauz K, Grayson I, Kleemann A, et al. (2006). "Amino Acids". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a02_057.pub2. ISBN   978-3527306732.
  14. 1 2 Tapiero H, Mathé G, Couvreur P, Tew KD (November 2002). "L-Arginine". (review). Biomedicine & Pharmacotherapy. 56 (9): 439–445. doi:10.1016/s0753-3322(02)00284-6. PMID   12481980.
  15. Wu G, Jaeger LA, Bazer FW, Rhoads JM (August 2004). "Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications". (review). The Journal of Nutritional Biochemistry. 15 (8): 442–51. doi: 10.1016/j.jnutbio.2003.11.010 . PMID   15302078.
  16. "Drugs and Supplements Arginine". Mayo Clinic . Retrieved 15 January 2015.
  17. Skipper A (1998). Dietitian's Handbook of Enteral and Parenteral Nutrition. Jones & Bartlett Learning. p. 76. ISBN   978-0-8342-0920-6.
  18. 1 2 Borlase BC (1994). Enteral Nutrition. Jones & Bartlett Learning. p. 48. ISBN   978-0-412-98471-6.
  19. Freedland RA, Briggs S (2012-12-06). A Biochemical Approach to Nutrition. Springer Science & Business Media. p. 45. ISBN   9789400957329.
  20. Nutrient Requirements of Dogs. National Academies Press. 1985. p. 65. ISBN   978-0-309-03496-8.
  21. 1 2 Wortinger A, Burns K (2015-06-11). Nutrition and Disease Management for Veterinary Technicians and Nurses. John Wiley & Sons. p. 232. ISBN   978-1-118-81108-5.
  22. Spano MA, Kruskall LJ, Thomas DT (2017-08-30). Nutrition for Sport, Exercise, and Health. Human Kinetics. p. 240. ISBN   978-1-4504-1487-6.
  23. 1 2 Watson RR, Zibadi S (2012-11-28). Bioactive Dietary Factors and Plant Extracts in Dermatology. Springer Science & Business Media. p. 75. ISBN   978-1-62703-167-7.
  24. Morris SM (October 2004). "Enzymes of arginine metabolism". (review). The Journal of Nutrition. 134 (10 Suppl): 2743S–2747S, discussion 2765S–2767S. doi: 10.1093/jn/134.10.2743S . PMID   15465778.
  25. Mauro C, Frezza C (2015-07-13). The Metabolic Challenges of Immune Cells in Health and Disease. Frontiers Media SA. p. 17. ISBN   9782889196227.
  26. Stechmiller JK, Childress B, Cowan L (February 2005). "Arginine supplementation and wound healing". (review). Nutrition in Clinical Practice. 20 (1): 52–61. doi:10.1177/011542650502000152. PMID   16207646.
  27. Witte MB, Barbul A (2003). "Arginine physiology and its implication for wound healing". (review). Wound Repair and Regeneration. 11 (6): 419–23. doi:10.1046/j.1524-475X.2003.11605.x. PMID   14617280. S2CID   21239136.
  28. Andrew PJ, Mayer B (August 1999). "Enzymatic function of nitric oxide synthases". (review). Cardiovascular Research. 43 (3): 521–31. doi: 10.1016/S0008-6363(99)00115-7 . PMID   10690324.
  29. Gokce N (October 2004). "L-arginine and hypertension". The Journal of Nutrition. 134 (10 Suppl): 2807S–2811S, discussion 2818S–2819S. doi: 10.1093/jn/134.10.2807S . PMID   15465790.
  30. Kibe R, Kurihara S, Sakai Y, et al. (2014). "Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice". Scientific Reports. 4 (4548): 4548. Bibcode:2014NatSR...4E4548K. doi: 10.1038/srep04548 . PMC   4070089 . PMID   24686447.
  31. Banerjee, Kasturi; Chattopadhyay, Agnibha; Banerjee, Satarupa (2022-07-01). "Understanding the association of stem cells in fetal development and carcinogenesis during pregnancy". Advances in Cancer Biology - Metastasis. 4: 100042. doi: 10.1016/j.adcanc.2022.100042 . ISSN   2667-3940. S2CID   248485831.
  32. Rodriguez, Paulo C.; Quiceno, David G.; Ochoa, Augusto C. (2006-10-05). "l-arginine availability regulates T-lymphocyte cell-cycle progression". Blood. 109 (4): 1568–1573. doi:10.1182/blood-2006-06-031856. ISSN   0006-4971. PMC   1794048 . PMID   17023580.
  33. Mathews CK, Van Holde KE, Ahern KG (2000). Biochemistry (3rd ed.). San Francisco, Calif.: Benjamin Cummings. pp.  180. ISBN   978-0805330663. OCLC   42290721.
  34. 1 2 Barnes MR (2007-04-16). Bioinformatics for Geneticists: A Bioinformatics Primer for the Analysis of Genetic Data. John Wiley & Sons. p. 326. ISBN   9780470026199.
  35. Kleanthous C (2000). Protein-protein Recognition. Oxford University Press. p. 13. ISBN   9780199637607.
  36. Griffiths & Unwin 2016, p. 275.
  37. Griffiths & Unwin 2016, p. 176.
  38. Gambardella J, Khondkar W, Morelli MB, Wang X, Santulli G, Trimarco V (August 2020). "Arginine and Endothelial Function". Biomedicines. 8 (8): 277. doi: 10.3390/biomedicines8080277 . PMC   7460461 . PMID   32781796.
  39. Fitch CA, Platzer G, Okon M, et al. (May 2015). "Arginine: Its pKa value revisited". Protein Science. 24 (5): 752–61. doi:10.1002/pro.2647. PMC   4420524 . PMID   25808204.
  40. MedlinePlus Encyclopedia : Growth hormone stimulation test
  41. Alba-Roth J, Müller OA, Schopohl J, von Werder K (December 1988). "Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion". The Journal of Clinical Endocrinology and Metabolism. 67 (6): 1186–9. doi:10.1210/jcem-67-6-1186. PMID   2903866. S2CID   7488757.
  42. Kanaley JA (January 2008). "Growth hormone, arginine and exercise". Current Opinion in Clinical Nutrition and Metabolic Care. 11 (1): 50–4. doi:10.1097/MCO.0b013e3282f2b0ad. PMID   18090659. S2CID   22842434.
  43. Forbes SC, Bell GJ (June 2011). "The acute effects of a low and high dose of oral L-arginine supplementation in young active males at rest". Applied Physiology, Nutrition, and Metabolism. 36 (3): 405–11. doi:10.1139/h11-035. PMID   21574873.
  44. Tankersley RW (March 1964). "Amino Acid Requirements of Herpes Simplex Virus in Human Cells". Journal of Bacteriology. 87 (3): 609–613. doi: 10.1128/jb.87.3.609-613.1964 . PMC   277062 . PMID   14127578.
  45. Tomblin FA, Lucas KH (February 2001). "Lysine for management of herpes labialis". American Journal of Health-System Pharmacy. 58 (4): 298–300, 304. doi: 10.1093/ajhp/58.4.298 . PMID   11225166.
  46. Mailoo VJ, Rampes S (June 2017). "Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence". Integrative Medicine. 16 (3): 42–46. PMC   6419779 . PMID   30881246.
  47. Dong JY, Qin LQ, Zhang Z, et al. (December 2011). "Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials". review. American Heart Journal. 162 (6): 959–65. doi:10.1016/j.ahj.2011.09.012. PMID   22137067.
  48. Gui S, Jia J, Niu X, et al. (March 2014). "Arginine supplementation for improving maternal and neonatal outcomes in hypertensive disorder of pregnancy: a systematic review". (review). Journal of the Renin-Angiotensin-Aldosterone System. 15 (1): 88–96. doi: 10.1177/1470320313475910 . PMID   23435582.
  49. Liu P, Jing Y, Collie ND, et al. (August 2016). "Altered brain arginine metabolism in schizophrenia". Translational Psychiatry. 6 (8): e871. doi: 10.1038/tp.2016.144 . PMC   5022089 . PMID   27529679.
  50. Rembold, Christopher M.; Ayers, Carlos R. (February 2003). "Oral L-arginine can reverse digital necrosis in Raynaud's phenomenon". Molecular and Cellular Biochemistry. 244 (1–2): 139–141. doi:10.1023/A:1022422932108. ISSN   0300-8177. PMID   12701823. S2CID   30249281.
  51. Shao A, Hathcock JN (April 2008). "Risk assessment for the amino acids taurine, L-glutamine and L-arginine". Regulatory Toxicology and Pharmacology. 50 (3): 376–99. doi:10.1016/j.yrtph.2008.01.004. PMID   18325648.
  52. 1 2 "L-Arginine". MedlinePlus, US National Institutes of Health. 13 October 2021. Retrieved 2021-05-27.

Sources