View source for Arginine

{{short description|Amino acid}}
{{chembox
| ImageFile = Arginin - Arginine.svg
| IUPACNames=Arginine
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageName = Skeletal formula of arginine
| ImageCaption = [[Skeletal formula]] of arginine
| ImageClass = skin-invert-image
| ImageFileL2 = Arginine-from-xtal-3D-bs-17.png
| ImageCaptionL2 = [[Ball-and-stick model]]
| ImageFileR2 = Arginine-from-xtal-3D-sf.png
| ImageCaptionR2 = [[Space-filling model]]
| OtherNames = 2-Amino-5-guanidinopentanoic acid
|Section1={{Chembox Identifiers
| index1_label = D/L
| index2_label = D
| index_label = L <!-- needs to be L arginine (natural isomer) so drugbank etc. take correct index_label -->
| index3_label = L HCl
| CASNo1 = 7200-25-1
| CASNo1_Ref = {{cascite|correct|CAS}}
| CASNo2 = 157-06-2
| CASNo2_Ref = {{cascite|correct|CAS}}
| CASNo = 74-79-3
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo3 = 1119-34-2
| CASNo3_Ref = {{cascite|correct|CAS}}
| PubChem1 = 232
| PubChem2 = 71070
| PubChem = 6322
| ChemSpiderID1 = 227
| ChemSpiderID1_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID2 = 64224
| ChemSpiderID2_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 6082
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| UNII1_Ref = {{fdacite|correct|FDA}}
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII3_Ref = {{fdacite|correct|FDA}}
| UNII1 = FL26NTK3EP
| UNII2 = R54Z304Z7C
| UNII = 94ZLA3W45F
| UNII3 = F7LTH1E20Y
| EINECS = 230-571-3
| DrugBank = DB00125
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| KEGG = C02385
| KEGG_Ref = {{keggcite|correct|kegg}}
| MeSHName = Arginine
| ChEBI = 29016
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEMBL2 = 212301
| ChEMBL2_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1485
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| RTECS = CF1934200 <small>''L''</small>
| IUPHAR_ligand = 721
| Beilstein = 1725411, 1725412 <small>''D''</small>, 1725413 <small>''L''</small>
| Gmelin = 364938 <small>''D''</small>
| 3DMet = B01331
| SMILES1 = C(CC(C(=O)O)N)CNC(=N)N
| Jmol1 = none  <!-- needs to be none because Jmol would show L if this SMILES were used -->
| SMILES = C(C[C@@H](C(=O)O)N)CNC(=N)N
| SMILES2 = C(C[C@H](C(=O)O)N)CNC(=N)N
| SMILES3 = [Cl-].NC(CCCNC(N)=[NH2+])C([O-])=O
| SMILES4 =  NC(CCCNC(N)=[NH2+])C([O-])=O
| SMILES4_Comment = L [[Zwitterion]]
| StdInChI = 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
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ODKSFYDXXFIFQN-BYPYZUCNSA-N
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| InChIKey1 = ODKSFYDXXFIFQN-UHFFFAOYSA-N
| InChIKey2 = ODKSFYDXXFIFQN-SCSAIBSYSA-N
}}
|Section2={{Chembox Properties
| C=6 | H=14 | N=4 | O=2
| Appearance = White crystals
| Odor = Odourless
| MeltingPtK = 533
| BoilingPtC = 368
| Solubility = 14.87 g/100 mL (20 °C)
| SolubleOther = slightly soluble in [[ethanol]]<br />insoluble in [[ethyl ether]]
| LogP = −1.652
| pKa = 2.18 (carboxyl), 9.09 (amino), 13.8 (guanidino)
}}
|Section5={{Chembox Thermochemistry
| DeltaHf = −624.9–−622.3 kJ mol<sup>−1</sup>
| DeltaHc = −3.7396–−3.7370 MJ mol<sup>−1</sup>
| Entropy = 250.6 J K<sup>−1</sup> mol<sup>−1</sup>
| HeatCapacity = 232.8 J K<sup>−1</sup> mol<sup>−1</sup> (at 23.7 °C)
}}
|Section6={{Chembox Pharmacology
| ATC_Supplemental = {{aTC|B05|XB01}} <small>''S''</small>
}}
|Section7={{Chembox Hazards
| ExternalSDS = {{URL|1=https://www.sigmaaldrich.com/US/en/sds/sigma/11009
|2=L-Arginine}}
| GHSPictograms = {{gHS exclamation mark}}
| GHSSignalWord = '''WARNING'''
| HPhrases = {{h-phrases|319}}
| PPhrases = {{p-phrases|305+351+338}}
| LD50 = 5110 mg/kg (rat, oral)
}}
|Section8={{Chembox Related
| OtherFunction_label = alkanoic acids
| OtherFunction = {{unbulleted list|[[n-Methyl-D-aspartic acid|''N''-Methyl-<small>D</small>-aspartic acid]]|[[beta-Methylamino-L-alanine|''beta''-Methylamino-<small>L</small>-alanine]]|[[Guanidinopropionic acid]]|[[Theanine]]|[[Pantothenic acid]]}}
| OtherCompounds = {{unbulleted list|[[Panthenol]]}}
}}
}}
'''Arginine''' is the [[amino acid]] with the formula (H<sub>2</sub>N)(HN)CN(H)(CH<sub>2</sub>)<sub>3</sub>CH(NH<sub>2</sub>)CO<sub>2</sub>H.  The molecule features a [[guanidinium|guanidino]] group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO<sub>2</sub><sup>−</sup>) and both the amino and guanidino groups are protonated, resulting in a cation. Only the {{sm|l}}-arginine (symbol '''Arg''' or '''R''') enantiomer is found naturally.<ref>{{cite web | url = http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html | title = Nomenclature and Symbolism for Amino Acids and Peptides | publisher = IUPAC-IUB Joint Commission on Biochemical Nomenclature | year = 1983 | access-date = 5 March 2018 | archive-url = https://web.archive.org/web/20081009023202/http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html | archive-date = 9 October 2008 | url-status = dead }}</ref> Arg residues are common components of [[protein]]s. It is [[Genetic code|encoded]] by the [[DNA codon table|codons]] CGU, CGC, CGA, CGG, AGA, and AGG.<ref>{{cite web|url=http://www.chem.qmul.ac.uk/iupac/AminoAcid/|title=Nomenclature and Symbolism for Amino Acids and Peptides|author=IUPAC-IUBMB Joint Commission on Biochemical Nomenclature|work=Recommendations on Organic & Biochemical Nomenclature, Symbols & Terminology etc|archive-url=https://web.archive.org/web/20070529233449/http://www.chem.qmul.ac.uk/iupac/AminoAcid/|archive-date=29 May 2007 |url-status=live|access-date=2007-05-17}}</ref> The guanidine group in arginine is the [[Precursor (chemistry)|precursor]] for the biosynthesis of [[nitric oxide]].<ref name=":0">{{Cite book|url=https://books.google.com/books?id=h5FugARr4bgC&pg=PA189|title=Nitric Oxide: Biology and Pathobiology| vauthors = Ignarro LJ |date=2000-09-13|publisher=Academic Press|isbn=978-0-08-052503-7|pages=189|language=en}}</ref> Like all amino acids, it is a white, water-soluble solid.
The one-letter symbol R was assigned to arginine for its phonetic similarity.<ref name=":02">{{Cite journal |date=10 July 1968 |title=IUPAC-IUB Commission on Biochemical Nomenclature A One-Letter Notation for Amino Acid Sequences |url=https://www.jbc.org/article/S0021-9258(19)34176-6/pdf |journal=Journal of Biological Chemistry |language=en |volume=243 |issue=13 |pages=3557–3559 |doi=10.1016/S0021-9258(19)34176-6|doi-access=free }}</ref>
==History==
Arginine was first isolated in 1886 from [[Lupinus luteus|yellow lupin]] seedlings by the German chemist [[Ernst Schulze (chemist)|Ernst Schulze]] and his assistant Ernst Steiger.<ref>{{Cite web|url=http://www.arginium.de/wp-content/uploads/2015/09/Biographie-Ernst-Schulze-Juli-2015.pdf|title=Biographie von Ernst Schulze| vauthors = Apel F |date=July 2015|access-date=2017-11-06 |archive-url=https://web.archive.org/web/20151117031718/http://www.arginium.de/wp-content/uploads/2015/09/Biographie-Ernst-Schulze-Juli-2015.pdf |archive-date=17 November 2015}}</ref><ref>{{cite journal| vauthors = Schulze E, Steiger E |date=1887|title=Ueber das Arginin|trans-title=On arginine|url=https://babel.hathitrust.org/cgi/pt?id=coo.31924078260597;view=1up;seq=55| journal=Zeitschrift für Physiologische Chemie|volume=11|issue=1–2|pages=43–65}}</ref> He named it from the Greek ''árgyros'' (ἄργυρος) meaning "silver" due to the silver-white appearance of arginine nitrate crystals.<ref>{{cite web |title=BIOETYMOLOGY: ORIGIN IN BIO-MEDICAL TERMS: arginine (Arg R) |url=https://bioetymology.blogspot.com/2012/03/arginin-arg-r.html |access-date=25 July 2019}}</ref> In 1897, Schulze and Ernst Winterstein (1865–1949) determined the structure of arginine.<ref>{{cite journal | vauthors = Schulze E, Winterstein E |title=Ueber ein Spaltungs-product des Arginins |trans-title=On a cleavage product of arginine |language=de |journal=Berichte der Deutschen Chemischen Gesellschaft |date=September 1897 |volume=30 |issue=3 |pages=2879–2882 |doi=10.1002/cber.18970300389 |url=https://zenodo.org/record/1684244 }} The structure for arginine is presented on p. 2882.</ref> Schulze and Winterstein synthesized arginine from [[ornithine]] and [[cyanamide]] in 1899,<ref>{{cite journal | vauthors = Schulze E, Winterstein E |title=Ueber die Constitution des Arginins |trans-title=On the constitution of arginine |language=de |journal=Berichte der Deutschen Chemischen Gesellschaft |date=October 1899 |volume=32 |issue=3 |pages=3191–3194 |doi=10.1002/cber.18990320385 |url=https://zenodo.org/record/1617372 }}</ref> but some doubts about arginine's structure lingered<ref>{{cite book | vauthors = Cohen JB |title=Organic Chemistry for Advanced Students, Part 3 |date=1919 |publisher=Longmans, Green & Co. |location=New York, New York, USA |page=140 |edition=2nd |url=https://books.google.com/books?id=NW3SAAAAMAAJ&pg=PA140}}</ref> until [[S.P.L. Sørensen|Sørensen's]] synthesis of 1910.<ref>{{cite journal | vauthors = Sölrensen SP |title=Über die Synthese des ''dl''-Arginins (α-Amino-δ-guanido-''n''-valeriansäure) und der isomeren α-Guanido-δ-amino-''n''-valeriansäure |trans-title=On the synthesis of racemic arginine (α-amino-δ-guanido-''n''-valeric acid) and of the isomeric α-guanido-δ-amino-''n''-valeric acid |language=de |journal=Berichte der Deutschen Chemischen Gesellschaft |date=January 1910 |volume=43 |issue=1 |pages=643–651 |doi=10.1002/cber.191004301109 |url=https://zenodo.org/record/2450981 }}</ref>
==Sources==
===Production===
It is traditionally obtained by [[hydrolysis]] of various cheap sources of protein, such as [[gelatin]].<ref>{{cite journal|title=d-Arginine Hydrochloride| vauthors = Brand E, Sandberg M |journal=Org. Synth.|year=1932|volume=12|page=4|doi=10.15227/orgsyn.012.0004}}</ref> It is obtained commercially by fermentation. In this way, 25-35 g/liter can be produced, using glucose as a carbon source.<ref name=Ullmann>{{Ullmann|first1=Karlheinz|last1=Drauz|first2=Ian|last2=Grayson|first3=Axel|last3=Kleemann|first4=Hans-Peter|last4=Krimmer|first5=Wolfgang|last5=Leuchtenberger|first6=Christoph|last6=Weckbecker |display-authors=3| name-list-style = vanc |year=2006|doi=10.1002/14356007.a02_057.pub2|title=Amino Acids}}</ref>
===Dietary sources===
Arginine is classified as a semiessential or conditionally [[essential amino acid]], depending on the developmental stage and health status of the individual.<ref name="tapiero">{{cite journal |vauthors=Tapiero H, Mathé G, Couvreur P, Tew KD | title = L-Arginine | journal = Biomedicine & Pharmacotherapy | date = November 2002 | volume = 56 | issue = 9 | pages = 439–445 | doi = 10.1016/s0753-3322(02)00284-6 | pmid = 12481980 | department = (review) }}</ref> Preterm infants are unable to synthesize arginine internally, making the amino acid nutritionally essential for them.<ref>{{cite journal | vauthors = Wu G, Jaeger LA, Bazer FW, Rhoads JM | title = Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications | journal = The Journal of Nutritional Biochemistry | volume = 15 | issue = 8 | pages = 442–51 | date = August 2004 | pmid = 15302078 | doi = 10.1016/j.jnutbio.2003.11.010 | department = (review) | doi-access = free }}</ref> Most healthy people do not need to supplement with arginine because it is a component of all protein-containing foods<ref name=mayo>{{cite web|title=Drugs and Supplements Arginine|website=[[Mayo Clinic]]|url=http://www.mayoclinic.org/drugs-supplements/arginine/background/hrb-20058733|access-date=15 January 2015}}</ref> and can be synthesized in the body from [[glutamine]] via [[citrulline]].<ref>{{Cite book|url=https://books.google.com/books?id=3qexy5Se3SoC&pg=PA76|title=Dietitian's Handbook of Enteral and Parenteral Nutrition| vauthors = Skipper A |date=1998|publisher=Jones & Bartlett Learning|isbn=978-0-8342-0920-6|pages=76|language=en}}</ref><ref name=":1">{{Cite book|url=https://books.google.com/books?id=1nRbFrSil40C&pg=PA48|title=Enteral Nutrition| vauthors = Borlase BC |date=1994|publisher=Jones & Bartlett Learning|isbn=978-0-412-98471-6|pages=48|language=en}}</ref> Additional, dietary arginine is necessary for otherwise healthy individuals temporarily under physiological stress, for example during recovery from burns, injury or sepsis,<ref name=":1" /> or if either of the major sites of arginine biosynthesis, the [[small intestine]] and [[kidney]]s, have reduced function, because the small bowel does the first step of the synthesizing process and the kidneys do the second.<ref name=":0" />
Arginine is an essential amino acid for birds, as they do not have a [[urea cycle]].<ref>{{Cite book|url=https://books.google.com/books?id=dFb7AwAAQBAJ&pg=PA45|title=A Biochemical Approach to Nutrition| vauthors = Freedland RA, Briggs S |date=2012-12-06|publisher=Springer Science & Business Media|isbn=9789400957329|pages=45|language=en}}</ref> For some carnivores, for example cats, dogs<ref>{{Cite book|url=https://books.google.com/books?id=LWC6PChg9ZEC&pg=PA65|title=Nutrient Requirements of Dogs |date=1985|publisher=National Academies Press|isbn=978-0-309-03496-8|pages=65|language=en}}</ref> and ferrets, arginine is essential,<ref name=":0" /> because after a meal, their highly efficient [[protein catabolism]] produces large quantities of [[ammonia]] which need <!-- quantities is plural -->to be processed through the urea cycle, and if not enough arginine is present, the resulting ammonia toxicity can be lethal.<ref name=":2">{{Cite book|url=https://books.google.com/books?id=mh7yCQAAQBAJ&pg=PA232|title=Nutrition and Disease Management for Veterinary Technicians and Nurses| vauthors = Wortinger A, Burns K |date=2015-06-11|publisher=John Wiley & Sons|isbn=978-1-118-81108-5|pages=232|language=en}}</ref> This is not a problem in practice, because meat contains sufficient arginine to avoid this situation.<ref name=":2" />
Animal sources of arginine include meat, dairy products, and eggs,<ref>{{Cite book|url=https://books.google.com/books?id=p_YtDwAAQBAJ&pg=PA240|title=Nutrition for Sport, Exercise, and Health| vauthors = Spano MA, Kruskall LJ, Thomas DT | name-list-style = vanc |date=2017-08-30|publisher=Human Kinetics|isbn=978-1-4504-1487-6|pages=240|language=en}}</ref><ref name=":3">{{Cite book|url=https://books.google.com/books?id=kzKqMAkJw3UC&pg=PA75|title=Bioactive Dietary Factors and Plant Extracts in Dermatology| vauthors = Watson RR, Zibadi S |date=2012-11-28|publisher=Springer Science & Business Media|isbn=978-1-62703-167-7|pages=75|language=en}}</ref> and plant sources include seeds of all types, for example grains, beans, and nuts.<ref name=":3" />
===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 [[Argininosuccinic acid|argininosuccinate]] that is synthesized, one molecule of [[adenosine triphosphate]] (ATP) is hydrolyzed to [[adenosine monophosphate]] (AMP), consuming two ATP equivalents.{{cn|date=July 2024}}
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.{{cn|date=July 2024}}
[[File:Arginine biosynthesis pathway.png|thumb|Arginine biosynthesis|center|500px]]
Arginine is made by the body as follows. The [[epithelial cell]]s of the [[small intestine]] produce citrulline, primarily from [[glutamine]] and [[glutamate]], which is secreted into the bloodstream which carries it to the [[proximal tubule cell]]s 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 [[Nitric oxide synthase#iNOS|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.<ref>{{cite journal | vauthors = Morris SM | title = Enzymes of arginine metabolism | journal = The Journal of Nutrition | volume = 134 | issue = 10 Suppl | pages = 2743S–2747S; discussion 2765S–2767S | date = October 2004 | pmid = 15465778 | doi = 10.1093/jn/134.10.2743S | department = (review) | doi-access = free }}</ref>
== Function ==
Arginine plays an important role in [[cell division]], [[wound healing]], removing ammonia from the body, [[immune function]],<ref>{{Cite book|url=https://books.google.com/books?id=Hc3rCgAAQBAJ&pg=PA17|title=The Metabolic Challenges of Immune Cells in Health and Disease| vauthors = Mauro C, Frezza C |date=2015-07-13|publisher=Frontiers Media SA|isbn=9782889196227|pages=17|language=en}}</ref> and the release of hormones.<ref name="tapiero"/><ref>{{cite journal | vauthors = Stechmiller JK, Childress B, Cowan L | title = Arginine supplementation and wound healing | journal = Nutrition in Clinical Practice | volume = 20 | issue = 1 | pages = 52–61 | date = February 2005 | pmid = 16207646 | doi = 10.1177/011542650502000152 | department = (review) }}</ref><ref>{{cite journal | vauthors = Witte MB, Barbul A | title = Arginine physiology and its implication for wound healing | journal = Wound Repair and Regeneration | volume = 11 | issue = 6 | pages = 419–23 | year = 2003 | pmid = 14617280 | doi = 10.1046/j.1524-475X.2003.11605.x | s2cid = 21239136 | department = (review) }}</ref> It is a precursor for the synthesis of [[nitric oxide]] (NO),<ref>{{cite journal | vauthors = Andrew PJ, Mayer B | title = Enzymatic function of nitric oxide synthases | journal = Cardiovascular Research | volume = 43 | issue = 3 | pages = 521–31 | date = August 1999 | pmid = 10690324 | doi = 10.1016/S0008-6363(99)00115-7 | department = (review) | doi-access = free}}</ref> making it important in the regulation of [[blood pressure]].<ref>{{cite journal | vauthors = Gokce N | title = L-arginine and hypertension | journal = The Journal of Nutrition | volume = 134 | issue = 10 Suppl | pages = 2807S–2811S; discussion 2818S–2819S | date = October 2004 | pmid = 15465790 | doi = 10.1093/jn/134.10.2807S | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kibe R, Kurihara S, Sakai Y et al | title = Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice | journal = Scientific Reports | volume = 4 | issue = 4548 | date = 2014 | page = 4548 | pmid = 24686447| doi = 10.1038/srep04548 | pmc = 4070089 | bibcode = 2014NatSR...4E4548K | doi-access = free }}</ref> Arginine is necessary for T-cells to function in the body, and can lead to their deregulation if depleted.<ref>{{Cite journal |last1=Banerjee |first1=Kasturi |last2=Chattopadhyay |first2=Agnibha |last3=Banerjee |first3=Satarupa |date=2022-07-01 |title=Understanding the association of stem cells in fetal development and carcinogenesis during pregnancy |journal=Advances in Cancer Biology - Metastasis |language=en |volume=4 |pages=100042 |doi=10.1016/j.adcanc.2022.100042 |s2cid=248485831 |issn=2667-3940|doi-access=free}}</ref><ref>{{Cite journal |last1=Rodriguez |first1=Paulo C. |last2=Quiceno |first2=David G. |last3=Ochoa |first3=Augusto C. |date=2006-10-05 |title=l-arginine availability regulates T-lymphocyte cell-cycle progression |url=https://doi.org/10.1182/blood-2006-06-031856 |journal=Blood |volume=109 |issue=4 |pages=1568–1573 |doi=10.1182/blood-2006-06-031856 |issn=0006-4971 |pmc=1794048 |pmid=17023580}}</ref>
===Proteins===
Arginine's side chain is [[Amphiphile|amphipathic]], because at physiological pH it contains a positively charged guanidinium group, which is highly polar, at the end of a hydrophobic [[Aliphatic compound|aliphatic]] hydrocarbon chain. Because globular proteins have hydrophobic interiors and hydrophilic surfaces,<ref>{{Cite book |title=Biochemistry|url=https://archive.org/details/biochemistry0003math|url-access=registration| vauthors = Mathews CK, Van Holde KE, Ahern KG |date=2000|publisher=Benjamin Cummings|isbn=978-0805330663|edition=3rd|location=San Francisco, Calif.|pages=[https://archive.org/details/biochemistry0003math/page/180 180]|oclc=42290721}}</ref> 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 bond]]ing and [[Salt bridge (protein and supramolecular)|salt bridges.]]<ref name=":4">{{Cite book|url=https://books.google.com/books?id=CN9sYPJdXs4C&pg=PA326|title=Bioinformatics for Geneticists: A Bioinformatics Primer for the Analysis of Genetic Data| vauthors = Barnes MR |date=2007-04-16|publisher=John Wiley & Sons|isbn=9780470026199 |pages=326 }}</ref> For this reason, it is frequently found at the interface between two proteins.<ref>{{Cite book|url=https://books.google.com/books?id=hbd8dlG7zkIC&pg=PA13|title=Protein-protein Recognition| vauthors = Kleanthous C |date=2000|publisher=Oxford University Press|isbn=9780199637607|pages=13|language=en}}</ref> The aliphatic part of the side chain sometimes remains below the surface of the protein.<ref name=":4" />
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 disease]]s.{{sfn|Griffiths|Unwin|2016|p=275}} Another post-translational modification of arginine involves [[methylation]] by protein [[methyltransferase]]s.{{sfn|Griffiths|Unwin|2016|p=176}}
===Precursor===
Arginine is the immediate precursor of nitric oxide, an important signaling molecule which can act as a [[Second messenger system|second messenger]], as well as an intercellular messenger which regulates vasodilation, and also has functions in the immune system's reaction to infection.{{cn|date=July 2024}}
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 [[polyamine]]s (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 <small>L</small>-arginine is considered a sign of a healthy [[endothelium]].<ref name="pmid32781796">{{cite journal |vauthors=Gambardella J, Khondkar W, Morelli MB, Wang X, Santulli G, Trimarco V |title=Arginine and Endothelial Function |journal=Biomedicines |volume=8 |issue=8 |date=August 2020 |page=277 |pmid=32781796 |pmc=7460461 |doi=10.3390/biomedicines8080277 |url= |doi-access=free }}</ref>
== Structure ==
[[File:Betaine Arginine.png|thumb|right|250px|Delocalization of charge in guanidinium group of {{sm|l}}-Arginine]]
The [[amino acid]] [[Substituent|side-chain]] of arginine consists of a 3-carbon [[aliphatic]] straight chain, the distal end of which is capped by a [[guanidine|guanidinium]] group, which has a [[Acid dissociation constant|p''K''<sub>a</sub>]] of 13.8,<ref>{{cite journal | vauthors = Fitch CA, Platzer G, Okon M, Garcia-Moreno BE, McIntosh LP |display-authors=3| title = Arginine: Its pKa value revisited | journal = Protein Science | volume = 24 | issue = 5 | pages = 752–61 | date = May 2015 | pmid = 25808204 | pmc = 4420524 | doi = 10.1002/pro.2647 }}</ref> and is therefore always protonated and positively charged at physiological pH. Because of the [[Conjugated system|conjugation]] between the double bond and the nitrogen [[lone pair]]s, the positive charge is delocalized, enabling the formation of multiple [[hydrogen bond]]s.
==Research==
===Growth hormone===
Intravenously administered arginine is used in growth hormone stimulation tests<ref>{{MedlinePlusEncyclopedia|003377|Growth hormone stimulation test}}</ref> because it stimulates the secretion of [[growth hormone]].<ref>{{cite journal | vauthors = Alba-Roth J, Müller OA, Schopohl J, von Werder K | s2cid = 7488757 | title = Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 67 | issue = 6 | pages = 1186–9 | date = December 1988 | pmid = 2903866 | doi = 10.1210/jcem-67-6-1186 }}</ref> A review of clinical trials concluded that oral arginine increases growth hormone, but decreases growth hormone secretion, which is normally associated with exercising.<ref>{{cite journal | vauthors = Kanaley JA | title = Growth hormone, arginine and exercise | journal = Current Opinion in Clinical Nutrition and Metabolic Care | volume = 11 | issue = 1 | pages = 50–4 | date = January 2008 | pmid = 18090659 | doi = 10.1097/MCO.0b013e3282f2b0ad | s2cid = 22842434 }}</ref> However, a more recent trial reported that although oral arginine increased plasma levels of <small>L</small>-arginine it did not cause an increase in growth hormone.<ref>{{cite journal | vauthors = Forbes SC, Bell GJ | title = The acute effects of a low and high dose of oral L-arginine supplementation in young active males at rest | journal = Applied Physiology, Nutrition, and Metabolism| volume = 36 | issue = 3 | pages = 405–11 | date = June 2011 | pmid = 21574873 | doi = 10.1139/h11-035 }}</ref>
===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".<ref>{{cite journal | vauthors = Tankersley RW |title=Amino Acid Requirements of Herpes Simplex Virus in Human Cells |journal=Journal of Bacteriology |date=March 1964 |volume=87 |issue=3 |pages=609–613 |doi=10.1128/jb.87.3.609-613.1964 |pmid=14127578 |pmc=277062 |doi-access=free }}</ref>
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.<ref>{{cite journal | vauthors = Tomblin FA, Lucas KH | title = Lysine for management of herpes labialis | journal = American Journal of Health-System Pharmacy | volume = 58 | issue = 4 | pages = 298–300, 304 | date = February 2001 | pmid = 11225166 | doi = 10.1093/ajhp/58.4.298 | doi-access = free }}</ref> 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."<ref>{{cite journal | vauthors = Mailoo VJ, Rampes S | title = Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence | journal = Integrative Medicine | volume = 16 | issue = 3 | pages = 42–46 | date = June 2017 | pmid = 30881246 | pmc = 6419779 }}</ref>
===High blood pressure===
A meta-analysis showed that <small>L</small>-arginine reduces blood pressure with pooled estimates of 5.4 mmHg for systolic blood pressure and 2.7 mmHg for diastolic blood pressure.<ref>{{cite journal | vauthors = Dong JY, Qin LQ, Zhang Z, Zhao Y, Wang J, Arigoni F, Zhang W |display-authors=3| title = Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials | journal = American Heart Journal | volume = 162 | issue = 6 | pages = 959–65 | date = December 2011 | pmid = 22137067 | doi = 10.1016/j.ahj.2011.09.012 | department = review }}</ref>
Supplementation with {{sm|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 [[Birth weight|weight at birth]].<ref>{{cite journal | vauthors = Gui S, Jia J, Niu X, Bai Y, Zou H, Deng J, Zhou R |display-authors=3| title = Arginine supplementation for improving maternal and neonatal outcomes in hypertensive disorder of pregnancy: a systematic review | journal = Journal of the Renin-Angiotensin-Aldosterone System | volume = 15 | issue = 1 | pages = 88–96 | date = March 2014 | pmid = 23435582 | doi = 10.1177/1470320313475910 | department = (review) | doi-access = free }}</ref>
===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.<ref>{{cite journal | vauthors = Liu P, Jing Y, Collie ND, Dean B, Bilkey DK, Zhang H |display-authors=3| title = Altered brain arginine metabolism in schizophrenia | journal = Translational Psychiatry | volume = 6 | issue = 8 | pages = e871 | date = August 2016 | pmid = 27529679 | pmc = 5022089 | doi = 10.1038/tp.2016.144 | doi-access = free }}</ref>
===Raynaud's phenomenon===
Oral L-arginine has been shown to reverse digital necrosis in [[Raynaud syndrome]]<ref>{{Cite journal |last1=Rembold |first1=Christopher M. |last2=Ayers |first2=Carlos R. |date=February 2003 |title=Oral L-arginine can reverse digital necrosis in Raynaud's phenomenon |url=https://pubmed.ncbi.nlm.nih.gov/12701823/ |journal=Molecular and Cellular Biochemistry |volume=244 |issue=1–2 |pages=139–141 |doi=10.1023/A:1022422932108 |issn=0300-8177 |pmid=12701823|s2cid=30249281 }}</ref>
==Safety and potential drug interactions==
L-arginine is recognized as safe (GRAS-status) at intakes of up to 20 grams per day.<ref>{{cite journal | vauthors = Shao A, Hathcock JN | title = Risk assessment for the amino acids taurine, L-glutamine and L-arginine | journal = Regulatory Toxicology and Pharmacology | volume = 50 | issue = 3 | pages = 376–99 | date = April 2008 | pmid = 18325648 | doi = 10.1016/j.yrtph.2008.01.004 }}</ref> L-arginine is found in many foods, such as fish, poultry, and dairy products, and is used as a dietary supplement.<ref name="mlp">{{Cite web|title=L-Arginine|url=https://medlineplus.gov/druginfo/natural/875.html|access-date=2021-05-27|publisher=MedlinePlus, US National Institutes of Health|date=13 October 2021|language=en}}</ref> It may interact with various [[prescription drug]]s and herbal supplements.<ref name=mlp/>
==See also==
* [[Arginine glutamate]]
* [[AAKG]]
* [[Canavanine]] and [[canaline]] are toxic [[analog (chemistry)|analogs]] of arginine and [[ornithine]].
==References==
{{reflist}}
==Sources==
* {{cite book | vauthors = Griffiths JR, Unwin RD |title=Analysis of Protein Post-Translational Modifications by Mass Spectrometry |date=2016 |publisher=John Wiley & Sons |isbn=978-1-119-25088-3 }}
== External links ==
{{Commons category|Arginine}}
* [http://webbook.nist.gov/cgi/cbook.cgi?ID=C74793&Units=SI&Mask=4#Thermo-Phase NIST Chemistry Webbook]
* [https://www.mayoclinic.org/drugs-supplements-l-arginine/art-20364681 L-arginine, Mayo Clinic]
{{Amino acids}}
{{Amino acid metabolism intermediates}}
{{Nitric oxide signaling}}
{{Authority control}}
[[Category:Proteinogenic amino acids]]
[[Category:Glucogenic amino acids]]
[[Category:Alpha-Amino acids]]
[[Category:Basic amino acids]]
[[Category:Guanidines]]
[[Category:Urea cycle]]