Ergothioneine

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Ergothioneine
Ergothioneine.svg Ergothioneine ball and stick.png
Ergothioneine 3D.png
Identifiers
CAS number 497-30-3 YesY
PubChem 5351619
ChemSpider 4508619 YesY
UNII BDZ3DQM98W YesY
ChEBI CHEBI:4828 YesY
Jmol-3D images Image 1
Image 2
Properties
Molecular formula C9H15N3O2S
Molar mass 229.30 g/mol
Appearance white solid
Melting point 275 to 277 °C (527 to 531 °F; 548 to 550 K)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
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 and filamentous fungi.[1] 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.[2] 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.[3] 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.[4][5]

Chemistry[edit]

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.[6] 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.[4] However, ergothioneine can be slowly oxidized over several days to the disulfide form in acidic solutions.[7] 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.[8]

Metabolism and sources[edit]

Ergothioneine has been found in bacteria, plants and animals, sometimes at millimolar levels.[4] Foods rich in ergothioneine include liver, kidney, black beans, kidney bean and oat bran, with the highest levels in bolete and oyster mushrooms.[4] 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,[2] and it is also present in the skin.[9]

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.[10] Biosynthesis has been detected in Actinobacteria, such as Mycobacterium smegmatis and filamentous fungi, such as Neurospora crassa.[1] Although the exact metabolic pathway is not clear, it is known that the imidazole ring is supplied by histidine, which is then methylated to produce histidine betaine, and then the sulfur atom incorporated from cysteine.[4][11] Other species of bacteria, such as Bacillus subtilis, Escherichia coli, Proteus vulgaris and Streptococcus, as well as fungi in the Saccharomycotina cannot make ergothioneine.[12][13]

Preliminary research[edit]

Ergothioneine has antioxidant properties in vitro.[1][14] Under laboratory conditions, it scavenges hydroxyl radicals and hypochlorous acid, inhibits production of oxidants by metal ions,[15][16] and may participate in metal ion transport and regulation of metalloenzymes.[16] As these properties were measured in cell-free systems, their relevance to actual function of ergothioneine in vivo remains unproven.[4]

In vitro, ergothioneine is transported into human cells by a specific transporter called ETT (gene symbol SLC22A4).[17][18] Mutants of this transporter are associated with the autoimmune disorders, rheumatoid arthritis and Crohn's disease.[4] Surprisingly, these mutant transporters are not impaired and instead can transport ergothioneine more efficiently than the normal forms of these proteins.[5] This may also relate to the fact that higher blood ergothioneine levels have been associated with rheumatoid arthritis.[19]

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.[4] One human study showed pain reduction and increased range of movement over six weeks of dietary supplementation.[20]

See also[edit]

References[edit]

  1. ^ a b c Fahey RC (2001). "Novel thiols of prokaryotes". Annu. Rev. Microbiol. 55: 333–56. doi:10.1146/annurev.micro.55.1.333. PMID 11544359. 
  2. ^ a b 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. 
  3. ^ Melville DB, Otken CC, Kovalenko V (September 1955). "On the origin of animal ergothioneine". J. Biol. Chem. 216 (1): 325–31. PMID 13252032. 
  4. ^ a b c d e f g h 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. 
  5. ^ a b 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. 
  6. ^ 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. 
  7. ^ Heath H, Toennies G (February 1958). "The preparation and properties of ergothioneine disulphide". Biochem. J. 68 (2): 204–10. PMC 1200325. PMID 13522601. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ Genghof DS (1 August 1970). "Biosynthesis of Ergothioneine and Hercynine by Fungi and Actinomycetales". J. Bacteriol. 103 (2): 475–8. PMC 248105. PMID 5432011. 
  13. ^ Genghof DS, Inamine E, Kovalenko V, Melville DB (November 1956). "Ergothioneine in microorganisms". J. Biol. Chem. 223 (1): 9–17. PMID 13376573. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ a b 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. 
  17. ^ 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. 
  18. ^ 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. [dead link]
  19. ^ 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. 
  20. ^ 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. 

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