Arginine

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of L-arginine
Structural formula of L- arginine, the naturally occurring enantiomer
General
Surname Arginine
other names
Molecular formula
  • C 6 H 14 N 4 O 2 (arginine)
  • C 6 H 14 N 4 O 2 HCl (arginine hydrochloride )
  • C 6 H 14 N 4 O 2 HCl H 2 O (arginine hydrochloride hydrate )
Brief description

white solid

External identifiers / databases
CAS number
  • 74-79-3 ( L- arginine)
  • 157-06-2 ( D- arginine)
  • 7200-25-1 (racemate)
  • 1119-34-2 ( L- arginine hydrochloride)
  • 332360-01-7 ( DL -arginine hydrochloride hydrate)
EC number 200-811-1
ECHA InfoCard 100,000,738
PubChem 6322
ChemSpider 6082
DrugBank DB00125
Wikidata Q173670
Drug information
ATC code
properties
Molar mass
  • 174.20 g mol −1 (arginine)
  • 210.66 g mol −1 (arginine hydrochloride)
  • 228.68 g mol −1 (arginine hydrochloride hydrate)
Physical state

firmly

density

0.7 g cm −3

Melting point

238 ° C

pK s value
  • COOH: 2.0
  • NH 2 : 9.0
  • Guanidine group: 12.1 (strongly basic)
solubility

good in water (150 g l −1 at 20 ° C)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 319
P: 305 + 351 + 338
Toxicological data

5110 mg kg −1 ( LD 50 ,  rat ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

L- arginine is a proteinogenic α - amino acid . It is semi- essential for humans. The name is derived from the Latin word argentum ( silver ), as the amino acid could first be isolated as a silver salt. This amino acid has the highest mass fraction of nitrogen of all proteinogenic amino acids. In the three-letter code is L Arginine with Arg and in one letter as R abbreviated.

Enantiomers

Arginine has a stereocenter, so there are two chiral enantiomers .

In the proteins, only L- arginine [synonym: ( S ) -arginine] occurs peptide- bound. The enantiomer of this is the mirror-image D -arginine [synonym: ( R ) -arginine], which does not occur in proteins. Racemic arginine [synonym: DL -arginine and ( RS ) -arginine] is of little importance.

If “arginine” is mentioned in texts or in scientific literature without any additional name ( prefix ), then L- arginine is meant.

Enantiomers of arginine
Surname L- arginine D- arginine
other names ( S ) -arginine ( R ) -arginine
Structural formula Structural formula of L-arginine Structural formula of D-arginine
CAS number 74-79-3 157-06-2
7200-25-1 (racemate)
EC number 200-811-1 205-866-5
230-571-3 (racemate)
ECHA info card 100,000,738 100.005.334
100.027.793 (racemate)
PubChem 6322 71070
232 (racemate)
DrugBank DB00125 DB04027
- (racemate)
Wikidata Q173670 Q27076987
Q27104032 (racemate)

Occurrence

L- arginine is widely used. The following examples give an overview of the arginine content and each relate to 100 g of the food , and the percentage of bound arginine in the total protein is also given.

Food protein Arginine proportion of
Buckwheat grains 13.25 g 0 982 mg 0 7.4%
Peas , dried 24.55 g 2188 mg 0 8.9%
Peanut , roasted 23.68 g 2832 mg 11.9%
Chicken breast fillet , raw 21.23 g 1436 mg 0 6.8%
Chicken egg 12.57 g 0 820 mg 0 6.5%
Cow's milk , 3.7% fat 0 3.28 g 0 119 mg 0 3.6%
Pumpkin seeds 30.23 g 5353 mg 17.7%
Salmon , raw 20.42 g 1221 mg 0 6.0%
Corn - whole wheat flour 0 6.93 g 0 345 mg 0 5.0%
Pine nuts 13.69 g 2413 mg 17.6%
Rice , unpeeled 0 7.94 g 0 602 mg 0 7.6%
Pork , raw 20.95 g 1394 mg 0 6.7%
Walnuts 15.23 g 2278 mg 15.0%
Whole wheat flour 13.70 g 0 642 mg 0 4.7%

All of these foods contain almost exclusively chemically bound L -arginine as a protein component , but no free L -arginine.

history

L- arginine was first isolated from lupine seedlings in 1886 by the German chemist Ernst Schulze and his doctoral student Ernst Steiger. In 1894 the Swedish chemist Sven Gustaf Hedin succeeded in isolating arginine from animal material through the hydrolytic cleavage of horny substance. By comparing his “animal” arginine with samples from the Schulzes laboratory that had been made available to him, Hedin was able to prove that the two substances corresponded.

properties

Zwitterions of L- arginine with the mesomerism-stabilized guanido cation

Arginine is an α- amino acid which in its side chain a hydrophilic , basic -reacting guanidino contains. This is protonated in the acidic, neutral and weakly basic medium, the positive charge being delocalized between the amino groups . Together with L - lysine and L - histidine , L- arginine belongs to the group of basic amino acids or hexonic bases .

Arginine is mainly present as an “inner salt” or zwitterion , the formation of which can be explained by the fact that the proton of the carboxy group migrates to the guanidino residue, which is more basic than the α-amino group.

The zwitterion does not migrate in the electric field because it is uncharged as a whole. Strictly speaking, this is the case at the isoelectric point (at a certain pH value, here 10.8), at which arginine also has its lowest solubility in water.

Free L- arginine has a bitter taste.

biosynthesis

In the urea cycle , L- arginine is formed from carbamoyl phosphate , L - ornithine and L - aspartate .

Industrial manufacturing processes

There are two processes for the production of L- arginine:

The L- arginine obtained in this way can optionally be converted into the more stable L- arginine hydrochloride in a further production step by reaction with hydrochloric acid .

Functions

L- arginine is a source of energy-rich nitrogen- phosphate compounds in organisms and is involved in numerous biological functions. It serves as a nitrogen reservoir in seedlings and storage cells. L- arginine is a metabolite of the urea cycle , in which the ammonia , which is formed when nitrogen compounds (e.g. amino acids) are broken down, is converted into urea . L- arginine is the sole precursor of nitric oxide (NO), one of the smallest messenger substances in the human body. By nitric oxide (NO) - synthase is produced from L arginine of endothelium-derived relaxing factor (EDRF), which was identified as NO. Physiologically, EDRF leads to vasodilation by diffusing the NO into the muscle layer of the vessels . There it activates the soluble guanylate cyclase and thus leads to the relaxation of the smooth muscles and a decrease in the vascular tone. Studies show that arginine can significantly lower high blood pressure through this vasodilation .

Due to its vasodilatory function, arginine is used in bodybuilding as a so-called “pump supplement”. Furthermore, the NO leads to the inhibition of platelet aggregation and adhesion. This reduces the propensity for thrombotic changes in vascular plaque ruptures, the most common cause of cerebral insults . It is believed that arginine can positively influence the suppressed immune response in severe injuries, malnutrition, sepsis and after operations. With additional administration, an improved cellular immune response, a decrease in injury-related functional disorders of the T cells and increased phagocytosis are observed. In addition, the development of endothelial dysfunction (impaired vascular function) is prevented.

In 1998 the scientists Robert F. Furchgott , Louis J. Ignarro and Ferid Murad received the Nobel Prize for Medicine for their research into the relationship between arginine and NO .

New studies also show that supplementation with arginine can promote the release of insulin from the beta cells of the pancreas and at the same time significantly reduce insulin resistance. In addition to the positive effect of L- arginine on glucose tolerance and on insulin sensitivity and production, L- arginine supplementation also leads to an improved antioxidant status.

Arginine antagonizes the dangerous effects of asymmetric dimethylarginine (ADMA) on blood vessels. ADMA decouples the formation of nitric oxide , which triggers endothelial dysfunction with nitrosative and oxidative stress.

requirement

Man can within the urea cycle arginine itself synthesize , but the quantities produced are not sufficient to meet the demand, especially among adolescent people to cover completely. Therefore, L- arginine is essential for children . But even in adults, the need for L- arginine is often not sufficiently covered by the body's own production. Especially in the growth phase, through stress, with various diseases (e.g. arteriosclerosis , high blood pressure , erectile dysfunction , vascular diseases) or after accidents, the need for arginine exceeds the amount produced by the human organism. The need for L- arginine also increases sharply in old age because the endogenous antagonist, asymmetric dimethylarginine (ADMA), increases by a factor of 4 and thus 40 times higher arginine concentrations are required to neutralize the dangerous effects of this mortality factor. These amounts can only be covered by a dietary intake. Factors such as oxidative and nitrosative stress as well as the ADMA level and thus the L- arginine-ADMA ratio are decisive for the requirement for L- arginine .

With a protein intake of around 70–90 g / day, the calculated daily arginine intake is around 1–5 g / day.

Medical use

L- arginine is used to treat severe metabolic alkalosis . In paediatrics, L- arginine is also indicated for the treatment of increased ammonia levels in the blood ( hyperammonaemia ) caused by a severe congenital metabolic disorder . Diagnostically is L -arginine for the clarification of a growth hormone deficiency in short stature used.

As a (semi) essential amino acid, L- arginine is a mandatory component of parenteral nutrition . L- arginine is also used in electrolyte concentrates for addition to infusion solutions and in peroral dietetics .

L- arginine hydrochloride is mostly used pharmaceutically .

Arginine is also used as an additive in toothpaste. Compared to a conventional toothpaste with added fluoride, improved remineralization was demonstrated with a combination of arginine, calcium carbonate and fluoride.

Supplements

Arginine is marketed for supplementation in the event of insufficient intake or increased need as a dietary food , especially as a food for special medical purposes , in accordance with diet regulations for various disease states such as erectile dysfunction , atherosclerosis in the early stages, dysfunction of the inner wall of blood vessels ( endothelial dysfunction ) and high blood pressure . These indications are established for the dietary treatment of the sick. Whether the intake of arginine improves exercise capacity or quality of life in patients with existing heart failure remains open - the results of a small, placebo-controlled study deny this.

The use of health claims which, on the other hand, show the contribution of L- arginine to healthy people to support the circulatory system (maintenance of normal blood flow, healthy blood pressure and hematopoiesis ), to support and improve erections and to strengthen muscles and concern the supply of nitrogen oxide in the metabolism, the European Food Safety Authority (EFSA) assessed 2011 as scientifically not justified. Individual studies confirm the health-promoting effects of L- arginine in healthy people as well as in arteriosclerosis, endothelial dysfunction and high blood pressure and recommend the amino acid for the therapy of the metabolic disorders underlying cardiovascular diseases, also in combination with vitamin B6, vitamin B12 and folic acid. A significant reduction in blood pressure was found, as was the case in the placebo group. The half-life of 6 grams of L-arginine is 1.5 to 2 hours.

literature

  • Jeremy M. Berg, John L. Tymoczko, Lubert Stryer : Biochemistry. 6th edition. Spectrum Akademischer Verlag, Heidelberg 2007, ISBN 978-3-8274-1800-5 .
  • Donald Voet, Judith G. Voet: Biochemistry. 3. Edition. John Wiley & Sons, New York 2004, ISBN 0-471-19350-X .
  • Bruce Alberts , Alexander Johnson, Peter Walter, Julian Lewis, Martin Raff, Keith Roberts: Molecular Biology of the Cell. 5th edition. Taylor & Francis, 2007, ISBN 978-0-8153-4106-2 .

Web links

Commons : Arginine  - Collection of pictures, videos and audio files
Wiktionary: Arginine  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. ↑ a b c d e data sheet arginine (PDF) from Carl Roth , accessed on March 13, 2010.
  2. ↑ a b c K.-J. Teresa et al: Nickel Ion Complexes of Amino Acids and Peptides. In: Metal Ions in Life Sciences. Volume 2: Nickel and Its Surprising Impact in Nature. John Wiley & Sons, 2007, ISBN 978-0-470-01671-8 , p. 67; doi: 10.1002 / 9780470028131.ch3 .
  3. ↑ a b Entry for CAS no. 74-79-3 in the GESTIS substance database of the IFA , accessed on March 9, 2011 (JavaScript required)
  4. ↑ nutrient database of the US Department of Agriculture , 22nd edition.
  5. ↑ E. Schulze: In: Reports of the German Chemical Society. Volume 19, 1886, pp. 1177ff.
  6. ↑ SG Hedin: In: Journal for physiological chemistry. Volume 20, 1895, p. 186.
  7. ↑ Sabine Hansen: Discovery of the amino acids. Berlin 2015 ( arginium.de ( memento from June 15, 2016 in the Internet Archive )).
  8. ↑ Hans-Dieter Jakubke, Hans Jeschkeit: Amino acids, peptides, proteins. Verlag Chemie, 1982, ISBN 3-527-25892-2 , p. 42.
  9. ^ Allinger , Cava , de Jongh , Johnson , Lebel , Stevens : Organic Chemistry. 1st edition. Walter de Gruyter, Berlin 1980, ISBN 3-11-004594-X , p. 1129.
  10. ↑ W. Ternes, A. Täufel, L. Tunger, M. Zobel (eds.): Food Lexicon. 4th edition. Behr's Verlag, Hamburg 2005, ISBN 3-89947-165-2 , pp. 62-63.
  11. ↑ Otto-Albrecht Neumüller (Ed.): Römpps Chemie-Lexikon. Volume 1: A-Cl. 8th revised and expanded edition. Franckh'sche Verlagshandlung, Stuttgart 1979, ISBN 3-440-04511-0 , pp. 263-264.
  12. ↑ a b J. Y. Dong, LQ Qin, Z. Zhang, Y. Zhao, J. Wang, F. Arigoni, W. Zhang: Effect of oral L-arginine supplementation on blood pressure: A meta-analysis of randomized, double-blind , placebo-controlled trials. In: At Heart. Volume 162, 2011, pp. 959-965, doi: 10.1016 / y.ahj.2011.09.012 .
  13. ↑ U. Landmesser et al .: Endothelial function: a critical determinant in atherosclerosis? In: Circulation. 109 (21 Suppl 1), 2004, pp. II27-II33. PMID 15173060 ; PDF (free full text access).
  14. ↑ P. Fürst, H.-K. Biesalki among others: nutritional medicine. Thieme-Verlag, Stuttgart 2004, pp. 94-95.
  15. ↑ LD Monti, E. Setola, PC Lucotti, MM Marrocco-Trischitta, M. Comola, E. Galluccio, A. Poggi, S. Mammì, AL Catapano, G. Comi, R. Chiesa, E. Bosi, PM Piatti: Effect of a long-term oral l-arginine supplementation on glucose metabolism: a randomized, double-blind, placebo-controlled trial. In: Diabetes Obes Metab. 14 (10), Oct 2012, pp. 893-900. doi: 10.1111 / j.1463-1326.2012.01615.x .
  16. ↑ LD Monti, MC Casiraghi, E. Setola, E. Galluccio, MA Pagani, L. Quaglia, E. Bosi, P. Piatti: L-arginine enriched biscuits improve endothelial function and glucose metabolism: a pilot study in healthy subjects and a cross-over study in subjects with impaired glucose tolerance and metabolic syndrome. In: Metabolism. 62 (2), Feb 2013, pp. 255-264. doi: 10.1016 / j.metabol.2012.08.004 .
  17. ↑ S. Fazelian, M. Hoseini, N. Namazi, J. Heshmati, M. Sepidar Kish, M. Mirfatahi, AS Some Olia: Effects of L- Arginine Supplementation on Antioxidant Status and Body Composition in Obese Patients with Pre-diabetes: A Randomized Controlled Clinical Trial. In: Adv Pharm Bull. 4 (Suppl 1), Oct 2014, pp. 449-454. doi: 10.5681 / apb.2014.066 .
  18. ↑ a b c d e f A. Ströhle, A. Hahn: Arginine in atherosclerosis: Dietary measures in atherosclerosis - importance of L-arginine. In: Deutsche Apotheker Zeitung. Part 1: Volume 20, 2012, pp. 97–102 ( online , free full text) and Part 2: Volume 21, pp. 74–83 ( online , free full text).
  19. ↑ a b c I. Seljeflot I., BB Nilsson, AS Westheim, V. Bratseth, H. Arnesen: The L-arginine-asymmetric dimethylarginine ratio is strongly related to the severity of chronic heart failure. No effects of exercise training. In: J. Cardiac. Fail. Volume 17, 2011, pp. 135-142, doi: 10.1016 / j.cardfail.2010.09.003 .
  20. ↑ a b M. Anderssohn, M. Rosenberg, E. Schwedhelm, C. Zugck, M. Lutz, N. Lüneburg, N. Frey, RH Böger: The L-Arginine-asymmetric dimethylarginine ratio is an independent predictor of mortality in dilated cardiomyopathy. In: J. Card. Fail. Volume 18, No. 12, 2012, pp. 904-911, doi: 10.1016 / j.cardfail.2012.10.011 .
  21. ↑ a b c F. Pizzarelli, R. Maas, P. Dattolo, G. Tripepi, S. Michelassi, G. D'Arrigo, M. Mieth, S. Bandinelli, L. Ferrucci, C. Zoccali: Asymmetric dimethylarginine predicts survival in the elderly. In: Age. Volume 35, No. 6, 2013, pp. 2465-2475 PMC 3824988 (free full text).
  22. ↑ a b c d S. M. Bode-Böger, J. Muke, A. Surdacki, G. Brabant, RH Böger, JC Frölich: Oral L-arginine improves endothelial function in healthy individuals older than 70 years. In: Vasc. Med. Volume 8, 2003, pp. 77-81, doi: 10.1191 / 1358863x03vm474oa (free full text).
  23. ↑ a b c d K. Jung, O. Petrowicz: L-arginine and folic acid in arteriosclerosis. Results of a prospective, multicenter consumption study. In: Perfusion. Volume 21, 2008, pp. 148-156.
  24. ↑ a b K. Sydow, RH Böger: Reloaded: ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst (e) inemia: effects of L-arginine and B vitamins. In: Cardiovasc. Res. 2012, doi: 10.1093 / cvr / cvs205 .
  25. ^ A. Hahn: Dietary supplements and supplementary balanced diets. Wissenschaftliche Verlagsgesellschaft, Stuttgart 2006, p. 295.
  26. ^ S. Ebel, HJ Roth (Ed.): Lexicon of Pharmacy. Georg Thieme Verlag, 1987, ISBN 3-13-672201-9 , p. 56.
  27. ^ R. Cantore, I. Petrou, S. Lavender, P. Santarpia, Z. Liu, E. Gittins, M. Vandeven, D. Cummins, R. Sullivan, N. Utgikar: In situ clinical effects of new dentifrices containing 1.5 % arginine and fluoride on enamel de- and remineralization and plaque metabolism. In: The Journal of clinical dentistry. Volume 24 Spec no A, 2013, pp. A32-A44. PMID 24156138 .
  28. ^ I. Petrou, R. Heu, M. Stranick, S. Lavender, L. Zaidel, D. Cummins, RJ Sullivan, C. Hsueh, JK Gimzewski: A breakthrough therapy for dentin hypersensitivity: how dental products containing 8% arginine and calcium carbonate work to deliver effective relief of sensitive teeth. In: The Journal of clinical dentistry. Volume 20, Number 1, 2009, pp. 23-31. PMID 19489189 .
  29. ↑ Iris Hinneburg: Arginine: protection of the heart and circulation not proven. In: Medicine transparent . June 30, 2020, accessed on July 13, 2020 (German).
  30. ↑ Carlo Agostoni, Jean-Louis Bresson, Susan Fairweather-Tait, Albert Flynn, Ines Golly, Hannu Korhonen, Pagona Lagiou, Martinus Løvik, Rosangela Marchelli, Ambroise Martin, Bevan Moseley, Monika Neuhäuser-Berthold, Hildegard Przyrembel, Seppo Salminen, Yolanda Sanz, Sean JJ Strain, Stephan Strobel, Inge Tetens, Daniel Tomé, Hendrik van Loveren, Hans Verhagen: Scientific Opinion on the substantiation of health claims related to L arginine and “immune system functions” (ID 455, 1713), growth or maintenance of muscle mass (ID 456, 1712, 4681), normal red blood cell formation (ID 456, 664, 1443, 1712), maintenance of normal blood pressure (ID 664, 1443), improvement of endothelium-dependent vasodilation (ID 664, 1443, 4680), “physical performance and condition” (ID 1820), “système nerveux” (ID 608), maintenance of normal erectile function (ID 649, 4682), contribution to normal spermatogenesis (ID 650, 4682), “function of the intestinal tract ”(ID 740), and maintenance of normal ammonia cle arance (ID 4683) pursuant to Article 13 (1) of Regulation (EC) No 1924/2006 . In: EFSA Journal . tape 9 , no. 4 , 2011, p. 2051–2081 , doi : 10.2903 / j.efsa.2011.2051 (free full text).
  31. ↑ P. Lucotti, L. Monti, E. Setola, G. La Canna, A. Castiglioni, A. Rossodivita, MG Pala, F. Formica, G. Paolini, AL Catapano, E. Bosi, O. Alfieri, P. Piatti: Oral L-arginine supplementation improves endothelial function and ameliorates insulin sensitivity and inflammation in cardiopathic nondiabetic patients after an aortocoronary bypass. In: Metabolism. Volume 58, No. 9, 2009, pp. 1270-1276, doi: 10.1016 / j.metabol.2009.03.029 .
  32. ↑ Y. Bai, L. Sun, T. Yang, K. Sun, R. Chen J. Hui: Increase in fasting vascular endothelial function after short-term oral L-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials. In: Am. J. Clin. Nutr. Volume 89, No. 1, 2009, pp. 77-84, doi: 10.3945 / ajcn.2008.26544 (free full text).
  33. ↑ JW Drover, R. Dhaliwal, L. Weitzel, PE Wischmeyer, JB Ochoa, DK Heyland: Perioperative use of arginine-supplemented diets: a systematic review of the evidence. In: J. Am. Coll. Surg. Volume 212, No. 3, 2011, pp. 385-399, doi: 10.1016 / j.jamcollsurg.2010.10.016 .
  34. ^ A b Daniel Menzel, Hermann Haller, Manfred Wilhelm, Horst Robenek: l-Arginine and B vitamins improve endothelial function in subjects with mild to moderate blood pressure elevation . In: European Journal of Nutrition . November 5, 2016, p. 1-12 , doi : 10.1007 / s00394-016-1342-6 .
  35. ↑ Arginine in atherosclerosis. May 24, 2012, accessed June 4, 2019 .