Ergothioneine

Ergothioneine
Names
IUPAC name
3-(2-Sulfanylidene-1,3-dihydroimidazol-4-yl)-2-(trimethylazaniumyl)propanoate
Other names
L-Ergothioneine; (+)-Ergothioneine; Thiasine; Sympectothion; Ergothionine; Erythrothioneine; Thiolhistidinebetaine
Identifiers
497-30-3 Yes
ChEBI CHEBI:4828 Yes
ChemSpider 4508619 Yes
Jmol-3D images Image
Image
KEGG C05570 Yes
PubChem 5351619
UNII BDZ3DQM98W Yes
Properties
C9H15N3O2S
Molar mass 229.30 g/mol
Appearance white solid
Melting point 275 °C (527 °F; 548 K)
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 Yes verify (what is: Yes/?)
Infobox references

Ergothioneine is a naturally occurring amino acid and is a thiourea derivative of histidine, containing a sulfur atom in the imidazole ring. This compound is made in rather few organisms, notably Actinobacteria, Cyanobacteria, and certain fungi.[1][2] Ergothioneine was discovered in 1909 and named after the ergot fungus from which it was first purified, with its structure being determined later, in 1911.[3] This amino acid has antioxidant properties, but its chemistry differs from conventional sulfur-containing antioxidants such as glutathione or lipoic acid.

Although ergothioneine cannot be made in human cells, it is present in some tissues at high levels as it is absorbed from the diet.[4] In humans ergothioneine is taken up from the gut and concentrated in some tissues by a specific transporter called ETT (gene symbol SLC22A4). However, even today, one hundred years after its discovery, precisely what ergothioneine does in the human body remains a mystery.[5][6]

Chemistry

Ergothioneine is a thiourea derivative of the betaine of histidine and contains a sulfur atom bonded to the 2-position of the imidazole ring. This compound is unusual since the sulfur atom is most stable in solution in the thione form, rather than the sulfhydryl, as is the case for the structurally related ovothiol.[7] This makes ergothioneine much less reactive than thiols such as glutathione towards alkylating agents like maleimides, and also prevents the compound from oxidizing in air.[5] However, ergothioneine can be slowly oxidized over several days to the disulfide form in acidic solutions.[8] If ergothioneine does become oxidized, the disulfide is a very strong oxidizing agent, so this will in turn rapidly oxidize other thiols in the cell such as glutathione.[9]

Metabolism and sources

Ergothioneine has been found in bacteria, plants and animals, sometimes at millimolar levels.[5] Foods rich in ergothioneine include liver, kidney, black beans, kidney bean and oat bran, with the highest levels in bolete and oyster mushrooms.[5] Levels can be variable, even within species and some tissues can contain much more than others. In the human body, the largest amounts of ergothioneine are found in erythrocytes, eye lens and semen,[3] and it is also present in the skin.[10]

Although many species contain ergothioneine, only a few can make it, the others absorb it from their diet or, in the case of plants, from their environment.[11] Biosynthesis has been detected in Actinobacteria, such as Mycobacterium smegmatis and certain fungi, such as Neurospora crassa.[1]

The metabolic pathway to produce ergothioneine starts with the methylation of histidine to produce histidine betaine (hercynine). The sulfur atom is then incorporated from cysteine.[5][12] The biosynthetic genes of ergothioneine have been described in Mycobacterium smegmatis,[13] Neurospora crassa,[14] and Schizosaccharomyces pombe.[15]

Other species of bacteria, such as Bacillus subtilis, Escherichia coli, Proteus vulgaris and Streptococcus, as well as fungi in the Saccharomycotina cannot make ergothioneine.[16][17]

Preliminary research

Ergothioneine has antioxidant properties in vitro.[1][18] Under laboratory conditions, it scavenges hydroxyl radicals and hypochlorous acid, inhibits production of oxidants by metal ions,[19][20] and may participate in metal ion transport and regulation of metalloenzymes.[20] As these properties were measured in cell-free systems, their relevance to actual function of ergothioneine in vivo remains unproven.[5]

In vitro, ergothioneine is transported into human cells by a specific transporter called ETT (gene symbol SLC22A4).[21][22] Mutants of this transporter are associated with the autoimmune disorders, rheumatoid arthritis and Crohn's disease.[5] Surprisingly, these mutant transporters are not impaired and instead can transport ergothioneine more efficiently than the normal forms of these proteins.[6] This may also relate to the fact that higher blood ergothioneine levels have been associated with rheumatoid arthritis.[23]

Since the function of ergothioneine in human metabolism remains unknown, whether these findings point to a direct role for this amino acid in human disease is unclear.[5][24] One human study showed pain reduction and increased range of movement over six weeks of dietary supplementation.[25]

Ergothioneine derivatives

Various derivatives of ergothioneine have been reported in the literature, such as S-methyl-ergothioneine[26] or selenium-containing selenoneine.[27]

See also

References

  1. ↑ 1.0 1.1 1.2 Fahey RC (2001). "Novel thiols of prokaryotes". Annu. Rev. Microbiol. 55: 333–56. doi:10.1146/annurev.micro.55.1.333. PMID 11544359.
  2. ↑ Pfeiffer, C; Bauer, T; Surek, B; Schömig, E; Gründemann, D (2011). "Cyanobacteria produce high levels of ergothioneine". Food Chemistry (Elsevier) 129 (4): 1766–1769. doi:10.1016/j.foodchem.2011.06.047.
  3. ↑ 3.0 3.1 Mann T, Leone E (January 1953). "Studies on the metabolism of semen. 8. Ergothioneine as a normal constituent of boar seminal plasma. Purification and crystallization. Site of formation and function". Biochem. J. 53 (1): 140–8. PMC 1198115. PMID 13032046.
  4. ↑ Melville DB, Otken CC, Kovalenko V (September 1955). "On the origin of animal ergothioneine". J. Biol. Chem. 216 (1): 325–31. PMID 13252032.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 Ey J, Schömig E, Taubert D (August 2007). "Dietary sources and antioxidant effects of ergothioneine". J. Agric. Food Chem. 55 (16): 6466–74. doi:10.1021/jf071328f. PMID 17616140.
  6. ↑ 6.0 6.1 Taubert D, Grimberg G, Jung N, Rubbert A, Schömig E (October 2005). "Functional role of the 503F variant of the organic cation transporter OCTN1 in Crohn's disease". Gut 54 (10): 1505–6. doi:10.1136/gut.2005.076083. PMC 1774715. PMID 16162962.
  7. ↑ Hartman PE (1990). "Ergothioneine as antioxidant". Meth. Enzymol. Methods in Enzymology 186: 310–8. doi:10.1016/0076-6879(90)86124-E. ISBN 978-0-12-182087-9. PMID 2172707.
  8. ↑ Heath H, Toennies G (February 1958). "The preparation and properties of ergothioneine disulphide" (PDF). Biochem. J. 68 (2): 204–10. PMC 1200325. PMID 13522601.
  9. ↑ Hand CE, Taylor NJ, Honek JF (March 2005). "Ab initio studies of the properties of intracellular thiols ergothioneine and ovothiol". Bioorg. Med. Chem. Lett. 15 (5): 1357–60. doi:10.1016/j.bmcl.2005.01.014. PMID 15713386.
  10. ↑ Markova NG, Karaman-Jurukovska N, Dong KK, Damaghi N, Smiles KA, Yarosh DB. (April 2009). "Skin cells and tissue are capable of using l-ergothioneine as an integral component of their antioxidant defense system". Free Radic Biol Med. 46 (8): 1168–76. doi:10.1016/j.freeradbiomed.2009.01.021. PMID 19439218.
  11. ↑ Audley, B.S.; Tan, C.H. (1968). "The uptake of ergothioneine from the soil into the latex of Hevea brasiliensis". Phytochemistry 7 (11): 1999–2000. doi:10.1016/S0031-9422(00)90759-3.
  12. ↑ Melville DB, Ludwig ML, Inamine E, Rachele JR (May 1959). "Transmethylation in the biosynthesis of ergothioneine". J. Biol. Chem. 234 (5): 1195–8. PMID 13654346.
  13. ↑ Seebeck, F. P. (2010). "In vitro reconstitution of Mycobacterial ergothioneine biosynthesis". Journal of the American Chemical Society 132 (19): 6632–3. doi:10.1021/ja101721e. PMID 20420449.
  14. ↑ Bello, M. H.; Barrera-Perez, V; Morin, D; Epstein, L (2012). "The Neurospora crassa mutant NcΔEgt-1 identifies an ergothioneine biosynthetic gene and demonstrates that ergothioneine enhances conidial survival and protects against peroxide toxicity during conidial germination". Fungal Genetics and Biology 49 (2): 160–72. doi:10.1016/j.fgb.2011.12.007. PMID 22209968.
  15. ↑ Pluskal, T; Ueno, M; Yanagida, M (2014). "Genetic and metabolomic dissection of the ergothioneine and selenoneine biosynthetic pathway in the fission yeast, S. Pombe, and construction of an overproduction system". PLoS ONE 9 (5): e97774. doi:10.1371/journal.pone.0097774. PMC 4020840. PMID 24828577.
  16. ↑ Genghof DS (1 August 1970). "Biosynthesis of Ergothioneine and Hercynine by Fungi and Actinomycetales". J. Bacteriol. 103 (2): 475–8. PMC 248105. PMID 5432011.
  17. ↑ Genghof DS, Inamine E, Kovalenko V, Melville DB (November 1956). "Ergothioneine in microorganisms". J. Biol. Chem. 223 (1): 9–17. PMID 13376573.
  18. ↑ Hand CE, Honek JF (February 2005). "Biological chemistry of naturally occurring thiols of microbial and marine origin". J. Nat. Prod. 68 (2): 293–308. doi:10.1021/np049685x. PMID 15730267.
  19. ↑ Akanmu D, Cecchini R, Aruoma OI, Halliwell B (July 1991). "The antioxidant action of ergothioneine". Arch Biochem Biophys 288 (1): 10–6. doi:10.1016/0003-9861(91)90158-F. PMID 1654816.
  20. ↑ 20.0 20.1 Misiti F, Castagnola M, Zuppi C, Giardina B, Messana I (June 2001). "Role of ergothioneine on S-nitrosoglutathione catabolism". Biochem J 356 (Pt 3): 799–804. doi:10.1042/0264-6021:3560799. PMC 1221906. PMID 11389687.
  21. ↑ Gründemann D, Harlfinger S, Golz S et al. (2005). "Discovery of the ergothioneine transporter". Proc. Natl. Acad. Sci. U.S.A. 102 (14): 5256–61. doi:10.1073/pnas.0408624102. PMC 555966. PMID 15795384.
  22. ↑ Nakamura T, Yoshida K, Yabuuchi H, Maeda T, Tamai I (August 2008). "Functional characterization of ergothioneine transport by rat organic cation/carnitine transporter Octn1 (slc22a4)" (– SCHOLAR SEARCH). Biol. Pharm. Bull. 31 (8): 1580–4. doi:10.1248/bpb.31.1580. PMID 18670092.
  23. ↑ Taubert D, Lazar A, Grimberg G et al. (November 2006). "Association of rheumatoid arthritis with ergothioneine levels in red blood cells: a case control study". J. Rheumatol. 33 (11): 2139–45. PMID 17086603.
  24. ↑ Cheah, I. K.; Halliwell, B (2012). "Ergothioneine; antioxidant potential, physiological function and role in disease". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1822 (5): 784–93. doi:10.1016/j.bbadis.2011.09.017. PMID 22001064.
  25. ↑ Benson K, Ager D, Landes B et al. (May 2012). "Improvement of joint range of motion (ROM) and reduction of chronic pain after consumption of an ergothioneine-containing nutritional supplement". Preventive Medicine 54: S83–9. doi:10.1016/j.ypmed.2012.02.001. PMID 22342951.
  26. ↑ Asmus, K. D.; Bensasson, R. V.; Bernier, J. L.; Houssin, R; Land, E. J. (1996). "One-electron oxidation of ergothioneine and analogues investigated by pulse radiolysis: Redox reaction involving ergothioneine and vitamin C". The Biochemical journal. 315 ( Pt 2): 625–9. PMC 1217242. PMID 8615839.
  27. ↑ Yamashita, Y; Yamashita, M (2010). "Identification of a novel selenium-containing compound, selenoneine, as the predominant chemical form of organic selenium in the blood of bluefin tuna". Journal of Biological Chemistry 285 (24): 18134–8. doi:10.1074/jbc.C110.106377. PMC 2881734. PMID 20388714.

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