Jump to content

Arginine

From Wikipedia, the free encyclopedia
Arginine
Skeletal formula of arginine
Skeletal formulaof arginine
Names
IUPAC names
Arginine
Other names
2-Amino-5-guanidinopentanoic acid
Identifiers
3D model (JSmol)
3DMet
1725411, 1725412D,1725413L
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.738Edit this at Wikidata
EC Number
  • L: 230-571-3
364938D
KEGG
MeSH Arginine
RTECS number
  • L: CF1934200L
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/s1checkY
    Key: ODKSFYDXXFIFQN-BYPYZUCNSA-NcheckY
  • 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
  • LZwitterion:NC(CCCNC(N)=[NH2+])C([O-])=O
Properties
C6H14N4O2
Molar mass 174.204g·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 inethanol
insoluble inethyl ether
logP −1.652
Acidity(pKa) 2.18 (carboxyl), 9.09 (amino), 13.8 (guanidino)
Thermochemistry
232.8 J K−1mol−1(at 23.7 °C)
250.6 J K−1mol−1
−624.9–−622.3 kJ mol−1
−3.7396–−3.7370 MJ mol−1
Pharmacology
B05XB01(WHO)S
Hazards
GHSlabelling:
GHS07: Exclamation mark
Warning
H319
P305+P351+P338
Lethal doseor 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 theirstandard state(at 25 °C [77 °F], 100 kPa).

Arginineis theamino acidwith the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features aguanidinogroup 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 thel-arginine (symbolArgorR) enantiomer is found naturally.[1]Arg residues are common components ofproteins.It isencodedby thecodonsCGU, CGC, CGA, CGG, AGA, and AGG.[2]The guanidine group in arginine is theprecursorfor the biosynthesis ofnitric oxide.[3]Like all amino acids, it is a white, water-soluble solid.

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

History

[edit]

Arginine was first isolated in 1886 fromyellow lupinseedlings by the German chemistErnst Schulzeand his assistant Ernst Steiger.[5][6]He named it from the Greekárgyros(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 fromornithineandcyanamidein 1899,[9]but some doubts about arginine's structure lingered[10]untilSørensen'ssynthesis of 1910.[11]

Sources

[edit]

Production

[edit]

It is traditionally obtained byhydrolysisof various cheap sources of protein, such asgelatin.[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

[edit]

Arginine is classified as a semiessential or conditionallyessential 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 fromglutamineviacitrulline.[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, thesmall intestineandkidneys,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 aurea cycle.[19]For some carnivores, for example cats, dogs[20]and ferrets, arginine is essential,[3]because after a meal, their highly efficientprotein catabolismproduces large quantities ofammoniawhich 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

[edit]

Arginine is synthesized fromcitrullinein the urea cycle by the sequential action of the cytosolic enzymesargininosuccinate synthetaseandargininosuccinate lyase.This is an energetically costly process, because for each molecule ofargininosuccinatethat is synthesized, one molecule ofadenosine triphosphate(ATP) is hydrolyzed toadenosine monophosphate(AMP), consuming two ATP equivalents.[citation needed]

The pathways linking arginine,glutamine,andprolineare bidirectional. Thus, the net use or production of these amino acids is highly dependent on cell type and developmental stage.[citation needed]

Arginine biosynthesis.

Arginine is made by the body as follows. Theepithelial cellsof thesmall intestineproduce citrulline, primarily fromglutamineandglutamate,which is secreted into the bloodstream which carries it to theproximal tubule cellsof thekidney,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 ofinducible 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 withnitrateandnitrite,the stable end-products of nitric oxide breakdown.[24]

Function

[edit]

Arginine plays an important role incell 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 ofnitric oxide(NO),[28]making it important in the regulation ofblood 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

[edit]

Arginine's side chain isamphipathic,because at physiological pH it contains a positively charged guanidinium group, which is highly polar, at the end of a hydrophobicaliphatichydrocarbon 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 inhydrogen bondingandsalt 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 apost-translational modificationprocess calledcitrullination.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 inautoimmune diseases.[36]Another post-translational modification of arginine involvesmethylationby proteinmethyltransferases.[37]

Precursor

[edit]

Arginine is the immediate precursor of nitric oxide, an important signaling molecule which can act as asecond messenger,as well as an intercellular messenger which regulates vasodilation, and also has functions in the immune system's reaction to infection.[citation needed]

Arginine is also a precursor forurea,ornithine,andagmatine;is necessary for the synthesis ofcreatine;and can also be used for the synthesis ofpolyamines(mainly through ornithine and to a lesser degree through agmatine, citrulline, and glutamate). The presence ofasymmetric dimethylarginine(ADMA), a close relative, inhibits the nitric oxide reaction; therefore, ADMA is considered a marker forvascular disease,just asL-arginine is considered a sign of a healthyendothelium.[38]

Structure

[edit]
Delocalization of charge in guanidinium group ofl-Arginine

Theamino acidside-chainof arginine consists of a 3-carbonaliphaticstraight chain, the distal end of which is capped by aguanidiniumgroup, which has apKaof 13.8,[39]and is therefore always protonated and positively charged at physiological pH. Because of theconjugationbetween the double bond and the nitrogenlone pairs,the positive charge is delocalized, enabling the formation of multiplehydrogen bonds.

Research

[edit]

Growth hormone

[edit]

Intravenously administered arginine is used in growth hormone stimulation tests[40]because it stimulates the secretion ofgrowth 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 ofL-arginine it did not cause an increase in growth hormone.[43]

Herpes-Simplex Virus (Cold sores)

[edit]

Research from 1964 into amino acid requirements ofherpes simplex virusin human cells indicated that "...the lack of arginine orhistidine,and possibly the presence oflysine,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 forherpes labialismay 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

[edit]

A meta-analysis showed thatL-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 withl-arginine reducesdiastolic blood pressureand lengthens pregnancy for women withgestational hypertension,including women with high blood pressure as part ofpre-eclampsia.It did not lower systolic blood pressure or improveweight at birth.[48]

Schizophrenia

[edit]

Both liquid chromatography and liquid chromatography/mass spectrometric assays have found that brain tissue of deceased people withschizophreniashows altered arginine metabolism. Assays also confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increasedagmatineconcentration 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

[edit]

Oral L-arginine has been shown to reverse digital necrosis inRaynaud syndrome[50]

Safety and potential drug interactions

[edit]

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 variousprescription drugsand herbal supplements.[52]

See also

[edit]

References

[edit]
  1. ^"Nomenclature and Symbolism for Amino Acids and Peptides".IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived fromthe originalon 9 October 2008.Retrieved5 March2018.
  2. ^IUPAC-IUBMB Joint Commission on Biochemical Nomenclature."Nomenclature and Symbolism for Amino Acids and Peptides".Recommendations on Organic & Biochemical Nomenclature, Symbols & Terminology etc.Archivedfrom the original on 29 May 2007.Retrieved2007-05-17.
  3. ^abcIgnarro LJ (2000-09-13).Nitric Oxide: Biology and Pathobiology.Academic Press. p. 189.ISBN978-0-08-052503-7.
  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 fromthe original(PDF)on 17 November 2015.Retrieved2017-11-06.
  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)".Retrieved25 July2019.
  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 desdl-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, Karlheinz; Grayson, Ian; Kleemann, Axel; et al. (2006). "Amino Acids".Ullmann's Encyclopedia of Industrial Chemistry.Weinheim: Wiley-VCH.doi:10.1002/14356007.a02_057.pub2.ISBN978-3527306732.{{cite encyclopedia}}:Unknown parameter|name-list-format=ignored (|name-list-style=suggested) (help)
  14. ^abTapiero 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.PMID12481980.
  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.PMID15302078.
  16. ^"Drugs and Supplements Arginine".Mayo Clinic.Retrieved15 January2015.
  17. ^Skipper A (1998).Dietitian's Handbook of Enteral and Parenteral Nutrition.Jones & Bartlett Learning. p. 76.ISBN978-0-8342-0920-6.
  18. ^abBorlase BC (1994).Enteral Nutrition.Jones & Bartlett Learning. p. 48.ISBN978-0-412-98471-6.
  19. ^Freedland RA, Briggs S (2012-12-06).A Biochemical Approach to Nutrition.Springer Science & Business Media. p. 45.ISBN9789400957329.
  20. ^Nutrient Requirements of Dogs.National Academies Press. 1985. p. 65.ISBN978-0-309-03496-8.
  21. ^abWortinger A, Burns K (2015-06-11).Nutrition and Disease Management for Veterinary Technicians and Nurses.John Wiley & Sons. p. 232.ISBN978-1-118-81108-5.
  22. ^Spano MA, Kruskall LJ, Thomas DT (2017-08-30).Nutrition for Sport, Exercise, and Health.Human Kinetics. p. 240.ISBN978-1-4504-1487-6.
  23. ^abWatson RR, Zibadi S (2012-11-28).Bioactive Dietary Factors and Plant Extracts in Dermatology.Springer Science & Business Media. p. 75.ISBN978-1-62703-167-7.
  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.PMID15465778.
  25. ^Mauro C, Frezza C (2015-07-13).The Metabolic Challenges of Immune Cells in Health and Disease.Frontiers Media SA. p. 17.ISBN9782889196227.
  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.PMID16207646.
  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.PMID14617280.S2CID21239136.
  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.PMID10690324.
  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.PMID15465790.
  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.PMC4070089.PMID24686447.
  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.ISSN2667-3940.S2CID248485831.
  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.ISSN0006-4971.PMC1794048.PMID17023580.
  33. ^Mathews CK, Van Holde KE, Ahern KG (2000).Biochemistry(3rd ed.). San Francisco, Calif.: Benjamin Cummings. pp.180.ISBN978-0805330663.OCLC42290721.
  34. ^abBarnes MR (2007-04-16).Bioinformatics for Geneticists: A Bioinformatics Primer for the Analysis of Genetic Data.John Wiley & Sons. p. 326.ISBN9780470026199.
  35. ^Kleanthous C (2000).Protein-protein Recognition.Oxford University Press. p. 13.ISBN9780199637607.
  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.PMC7460461.PMID32781796.
  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.PMC4420524.PMID25808204.
  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.PMID2903866.S2CID7488757.
  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.PMID18090659.S2CID22842434.
  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.PMID21574873.
  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.PMC277062.PMID14127578.
  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.PMID11225166.
  46. ^Mailoo VJ, Rampes S (June 2017)."Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence".Integrative Medicine.16(3): 42–46.PMC6419779.PMID30881246.
  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.PMID22137067.
  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.PMID23435582.
  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.PMC5022089.PMID27529679.
  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.ISSN0300-8177.PMID12701823.S2CID30249281.
  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.PMID18325648.
  52. ^ab"L-Arginine".MedlinePlus, US National Institutes of Health. 13 October 2021.Retrieved2021-05-27.

Sources

[edit]
  • Griffiths JR, Unwin RD (2016).Analysis of Protein Post-Translational Modifications by Mass Spectrometry.John Wiley & Sons.ISBN978-1-119-25088-3.
[edit]
Wikimedia Commons has media related toArginine.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Arginine&oldid=1233933065"