Carnosine

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Carnosine
Carnosine.svg
Names
IUPAC name
β-Alanylhistidine
Systematic IUPAC name
(2S)-2-(3-Aminopropanamido)-3-(3H-imidazol-4-yl)propanoic acid
Other names
β-Alanyl-L-histidine
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.005.610 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C9H14N4O3/c10-2-1-8(14)13-7(9(15)16)3-6-4-11-5-12-6/h4-5,7H,1-3,10H2,(H,11,12)(H,13,14)(H,15,16)/t7-/m0/s1 Yes check.svgY
    Key: CQOVPNPJLQNMDC-ZETCQYMHSA-N Yes check.svgY
  • InChI=1/C9H14N4O3/c10-2-1-8(14)13-7(9(15)16)3-6-4-11-5-12-6/h4-5,7H,1-3,10H2,(H,11,12)(H,13,14)(H,15,16)/t7-/m0/s1
    Key: CQOVPNPJLQNMDC-ZETCQYMHBX
  • O=C(O)C(NC(=O)CCN)Cc1c[nH]cn1
  • c1c(nc[nH]1)C[C@@H](C(=O)O)NC(=O)CCN
Properties
C9H14N4O3
Molar mass 226.236 g·mol−1
AppearanceCrystalline solid
Melting point 253 °C (487 °F; 526 K) (decomposition)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Carnosine (beta-alanyl-L-histidine) is a dipeptide molecule, made up of the amino acids beta-alanine and histidine. It is highly concentrated in muscle and brain tissues.[ citation needed ] Carnosine was discovered by Russian chemist Vladimir Gulevich. [1]

Contents

Carnosine is naturally produced by the body in the liver [2] from beta-alanine and histidine. Like carnitine, carnosine is composed of the root word carn, meaning "flesh", alluding to its prevalence in meat. [3] There are no plant-based sources of carnosine. [4] Carnosine is readily available as a synthetic nutritional supplement.

Carnosine can chelate divalent metal ions. [5] Carnosine is also considered a geroprotectant. [6]

Products containing carnosine are also used in topical preparations to reduce wrinkles on the skin. [7]

Carnosine may increase the Hayflick limit in human fibroblasts, it also appears to reduce the rate of telomere shortening. [8] This could potentially promote the growth of certain cancers that thrive due to telomere preservation. [7]

Biosynthesis

Carnosine is synthesized within the body from beta-alanine and histidine. Beta-alanine is a product of pyrimidine catabolism [9] and histidine is an essential amino acid. Since beta-alanine is the limiting substrate, supplementing just beta-alanine effectively increases the intramuscular concentration of carnosine. [10] [11]

Physiological effects

pH buffer

Carnosine has a pKa value of 6.83, making it a good buffer for the pH range of animal muscles. [12] Since beta-alanine is not incorporated into proteins, carnosine can be stored at relatively high concentrations (millimolar). Occurring at 17–25 mmol/kg (dry muscle), [13] carnosine (β-alanyl-L-histidine) is an important intramuscular buffer, constituting 10-20% of the total buffering capacity in type I and II muscle fibres.

Anti-oxidant

Carnosine has been shown to scavenge reactive oxygen species (ROS) as well as alpha-beta unsaturated aldehydes formed from peroxidation of cell membrane fatty acids during oxidative stress. It also buffers pH in muscle cells, and acts as a neurotransmitter in the brain. It is also a zwitterion, a neutral molecule with a positive and negative end.[ citation needed ]

Antiglycating

Carnosine acts as an antiglycating agent, reducing the rate of formation of advanced glycation end-products (substances that can be a factor in the development or worsening of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney failure, and Alzheimer's disease [14] ), and ultimately reducing development of atherosclerotic plaque build-up. [15] [16] [17]

Geroprotective

Carnosine is considered as a geroprotector. [18] Carnosine can increase the Hayflick limit in human fibroblasts, [19] as well as appearing to reduce the telomere shortening rate. [20] Carnosine may also slow aging through its anti-glycating properties (chronic glycolyating is speculated to accelerate aging). [21]

Other

Carnosine can chelate divalent metal ions. [15] [22] It has been suggested that binding Ca2+ may displace protons, thereby providing a link between Ca2+ and H+ buffering. [23] However, there is still controversy as to how much Ca2+ is bound to carnosine under physiological conditions. [24]

See also

References

  1. ↑ Gulewitsch, Wl.; Amiradžibi, S. (1900). "Ueber das Carnosin, eine neue organische Base des Fleischextractes". Berichte der Deutschen Chemischen Gesellschaft. 33 (2): 1902–1903. doi:10.1002/cber.19000330275.
  2. ↑ Trexler, Eric T.; Smith-Ryan, Abbie E.; Stout, Jeffrey R.; Hoffman, Jay R.; Wilborn, Colin D.; Sale, Craig; Kreider, Richard B.; Jäger, Ralf; Earnest, Conrad P.; Bannock, Laurent; Campbell, Bill (2015-07-15). "International society of sports nutrition position stand: Beta-Alanine". Journal of the International Society of Sports Nutrition. 12: 30. doi: 10.1186/s12970-015-0090-y . ISSN   1550-2783. PMC   4501114 . PMID   26175657.
  3. ↑ Hipkiss, A. R. (2006). "Does chronic glycolysis accelerate aging? Could this explain how dietary restriction works?". Annals of the New York Academy of Sciences. 1067 (1): 361–8. Bibcode:2006NYASA1067..361H. doi:10.1196/annals.1354.051. PMID   16804012. S2CID   41175541.
  4. ↑ Alan R. Hipkiss (2009). "Chapter 3: Carnosine and Its Possible Roles in Nutrition and Health". Advances in Food and Nutrition Research.
  5. ↑ Reddy, V. P.; Garrett, MR; Perry, G; Smith, MA (2005). "Carnosine: A Versatile Antioxidant and Antiglycating Agent". Science of Aging Knowledge Environment. 2005 (18): pe12. doi:10.1126/sageke.2005.18.pe12. PMID   15872311.
  6. ↑ Boldyrev, A. A.; Stvolinsky, S. L.; Fedorova, T. N.; Suslina, Z. A. (2010). "Carnosine as a natural antioxidant and geroprotector: From molecular mechanisms to clinical trials". Rejuvenation Research. 13 (2–3): 156–8. doi:10.1089/rej.2009.0923. PMID   20017611.
  7. 1 2 Schwarz, E; Guest, P C; Rahmoune, H; Wang, L; Levin, Y; Ingudomnukul, E; Ruta, L; Kent, L; et al. (2010). "Sex-specific serum biomarker patterns in adults with Asperger's syndrome" (PDF). Molecular Psychiatry. 16 (12): 1213–20. doi:10.1038/mp.2010.102. PMID   20877284.
  8. ↑ Shao, Lan; Li, Qing-Huan; Tan, Zheng (2004). "L-Carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts". Biochemical and Biophysical Research Communications. 324 (2): 931–6. doi:10.1016/j.bbrc.2004.09.136. PMID   15474517.
  9. ↑ "beta-ureidopropionate + H2O => beta-alanine + NH4+ + CO2". reactome. Archived from the original on 2013-10-23. Retrieved 2020-02-08. Cytosolic 3-ureidopropionase catalyzes the reaction of 3-ureidopropionate and water to form beta-alanine, CO2, and NH3 (van Kuilenberg et al. 2004).
  10. ↑ Derave W, Ozdemir MS, Harris R, Pottier A, Reyngoudt H, Koppo K, Wise JA, Achten E (August 9, 2007). "Beta-alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters". J Appl Physiol. 103 (5): 1736–43. doi:10.1152/japplphysiol.00397.2007. PMID   17690198. S2CID   6990201.
  11. ↑ Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, Kim CK, Wise JA (2007). "Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity". Amino Acids. 32 (2): 225–33. doi:10.1007/s00726-006-0364-4. PMID   16868650. S2CID   23988054.
  12. ↑ Bate-Smith, EC (1938). "The buffering of muscle in rigor: protein, phosphate and carnosine". Journal of Physiology. 92 (3): 336–343. doi:10.1113/jphysiol.1938.sp003605. PMC   1395289 . PMID   16994977.
  13. ↑ Mannion, AF; Jakeman, PM; Dunnett, M; Harris, RC; Willan, PLT (1992). "Carnosine and anserine concentrations in the quadriceps femoris muscle of healthy humans". Eur. J. Appl. Physiol. 64 (1): 47–50. doi:10.1007/BF00376439. PMID   1735411. S2CID   24590951.
  14. ↑ Vistoli, G; De Maddis, D; Cipak, A; Zarkovic, N; Carini, M; Aldini, G (Aug 2013). "Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation". Free Radic. Res. 47: Suppl 1:3–27. doi: 10.3109/10715762.2013.815348 . PMID   23767955. S2CID   207517855.
  15. 1 2 Reddy, V. P.; Garrett, MR; Perry, G; Smith, MA (2005). "Carnosine: A Versatile Antioxidant and Antiglycating Agent". Science of Aging Knowledge Environment. 2005 (18): pe12. doi:10.1126/sageke.2005.18.pe12. PMID   15872311.
  16. ↑ Rashid, Imran; Van Reyk, David M.; Davies, Michael J. (2007). "Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro". FEBS Letters. 581 (5): 1067–70. Bibcode:2007FEBSL.581.1067R. doi:10.1016/j.febslet.2007.01.082. PMID   17316626. S2CID   46535145.
  17. ↑ Hipkiss, A. R. (2005). "Glycation, ageing and carnosine: Are carnivorous diets beneficial?". Mechanisms of Ageing and Development. 126 (10): 1034–9. doi:10.1016/j.mad.2005.05.002. PMID   15955546. S2CID   19979631.
  18. ↑ Boldyrev, A. A.; Stvolinsky, S. L.; Fedorova, T. N.; Suslina, Z. A. (2010). "Carnosine as a natural antioxidant and geroprotector: From molecular mechanisms to clinical trials". Rejuvenation Research. 13 (2–3): 156–8. doi:10.1089/rej.2009.0923. PMID   20017611.
  19. ↑ McFarland, G; Holliday, R (1994). "Retardation of the Senescence of Cultured Human Diploid Fibroblasts by Carnosine". Experimental Cell Research. 212 (2): 167–75. doi:10.1006/excr.1994.1132. PMID   8187813.
  20. ↑ Shao, Lan; Li, Qing-Huan; Tan, Zheng (2004). "L-Carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts". Biochemical and Biophysical Research Communications. 324 (2): 931–6. doi:10.1016/j.bbrc.2004.09.136. PMID   15474517.
  21. ↑ Hipkiss, A. R. (2006). "Does Chronic Glycolysis Accelerate Aging? Could This Explain How Dietary Restriction Works?". Annals of the New York Academy of Sciences. 1067 (1): 361–8. Bibcode:2006NYASA1067..361H. doi:10.1196/annals.1354.051. PMID   16804012. S2CID   41175541.
  22. ↑ Abate, Chiara; Cassone, Giuseppe; Cordaro, Massimiliano; Giuffrè, Ottavia; Mollica-Nardo, Viviana; Ponterio, Rosina Celeste; Saija, Franz; Sponer, Jiri; Trusso, Sebastiano; Foti, Claudia (2021). "Understanding the behaviour of carnosine in aqueous solution: an experimental and quantum-based computational investigation on acid–base properties and complexation mechanisms with Ca 2+ and Mg 2+" . New Journal of Chemistry. 45 (43): 20352–20364. doi:10.1039/D1NJ04094D. ISSN   1144-0546.
  23. ↑ Swietach, Pawel; Youm, Jae-Boum; Saegusa, Noriko; Leem, Chae-Hun; Spitzer, Kenneth W.; Vaughan-Jones, Richard D. (2013-05-28). "Coupled Ca2+/H+ transport by cytoplasmic buffers regulates local Ca2+ and H+ ion signaling". Proceedings of the National Academy of Sciences of the United States of America. 110 (22): E2064–2073. doi: 10.1073/pnas.1222433110 . ISSN   1091-6490. PMC   3670334 . PMID   23676270.
  24. ↑ Eisner, David; Neher, Erwin; Taschenberger, Holger; Smith, Godfrey (2023-06-16). "Physiology of intracellular calcium buffering" (PDF). Physiological Reviews. 103 (4): 2767–2845. doi: 10.1152/physrev.00042.2022 . ISSN   1522-1210. PMID   37326298.
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