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Ergothioneine

Names
IUPAC name 3-(2-sulfanylidene-1,3-dihydroimidazol-4-yl)-2-(trimethylazaniumyl)propanoate
Other names L-Ergothioneine
Identifiers
CAS Number	497-30-3
3D model (JSmol)	Interactive image Interactive image
ChEBI	CHEBI:4828
ChemSpider	4508619
ECHA InfoCard	100.007.131
PubChem CID	5351619
UNII	BDZ3DQM98W
CompTox Dashboard (EPA)	DTXSID901020082
InChI InChI=1S/C9H15N3O2S/c1-12(2,3)7(8(13)14)4-6-5-10-9(15)11-6/h5,7H,4H2,1-3H3,(H2-,10,11,13,14,15)/t7-/m0/s1Key: SSISHJJTAXXQAX-ZETCQYMHSA-N InChI=1/C9H15N3O2S/c1-12(2,3)7(8(13)14)4-6-5-10-9(15)11-6/h5,7H,4H2,1-3H3,(H2-,10,11,13,14,15)/t7-/m0/s1Key: SSISHJJTAXXQAX-ZETCQYMHBA
SMILES C(C)(C)C(CC1=CNC(=S)N1)C(=O) S=C1N\C(=C/N1)C(C()=O)(C)(C)C
Properties
Chemical formula	C9H15N3O2S
Molar mass	229.30 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Y verify (what is  ?) 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. 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. 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. 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.

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. 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. However, ergothioneine can be slowly oxidized over several days to the disulfide form in acidic solutions. 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.

Metabolism and sources

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

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. Biosynthesis has been detected in Actinobacteria, such as Mycobacterium smegmatis and filamentous fungi, such as Neurospora crassa. 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. Other species of bacteria, such as Bacillus subtilis, Escherichia coli, Proteus vulgaris and Streptococcus, as well as fungi belonging to the groups Ascomycetes and Deuteromycetes, cannot make ergothioneine.

Possible functions

Despite its unusual chemistry, ergothioneine does still have antioxidant properties. It is a good scavenger of hydroxyl radicals and hypochlorous acid, and can inhibit the production of oxidants by metal ions. On the other hand, since these antioxidant properties were measured in simple cell-free systems, their relevance to the actual function of ergothioneine in the body has been questioned. Another possibility is that ergothioneine is important in protecting cells against the nitrosative stress produced by reactive nitrogen species such as nitric oxide. However, it might also be involved in metal ion transport and the regulation of metalloenzymes.

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

See also

• Natural product
• Oxidative stress
• Reactive oxygen species
• Medicinal mushrooms

References

1. ^ Fahey RC (2001). "Novel thiols of prokaryotes". Annu. Rev. Microbiol. 55: 333–56. doi:10.1146/annurev.micro.55.1.333. PMID 11544359.
2. ^ Mann T, Leone E (1953). "Studies on the metabolism of semen. VIII. 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. {{cite journal}}: Unknown parameter |month= ignored (help)
3. Melville DB, Otken CC, Kovalenko V (1955). "On the origin of animal ergothioneine". J. Biol. Chem. 216 (1): 325–31. PMID 13252032. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
4. ^ Ey J, Schömig E, Taubert D (2007). "Dietary sources and antioxidant effects of ergothioneine". J. Agric. Food Chem. 55 (16): 6466–74. doi:10.1021/jf071328f. PMID 17616140. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
5. ^ Taubert D, Grimberg G, Jung N, Rubbert A, Schömig E (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
6. Hartman PE (1990). "Ergothioneine as antioxidant". Meth. Enzymol. 186: 310–8. doi:10.1016/0076-6879(90)86124-E. PMID 2172707.
7. Heath H, Toennies G (1958). "The preparation and properties of ergothioneine disulphide" (PDF). Biochem. J. 68 (2): 204–10. PMC 1200325. PMID 13522601. {{cite journal}}: Unknown parameter |month= ignored (help)
8. Hand CE, Taylor NJ, Honek JF (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
9. Markova NG, Karaman-Jurukovska N, Dong KK, Damaghi N, Smiles KA, Yarosh DB. (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
10. Audley, B.S.; Tan, C.H. (1968). "The uptake of ergothioneine from the soil into the latex of Hevea brasiliensis". Phytochemistry. 7: 1999–2000. doi:10.1016/S0031-9422(00)90759-3.
11. MELVILLE DB, LUDWIG ML, INAMINE E, RACHELE JR (1959). "Transmethylation in the biosynthesis of ergothioneine". J. Biol. Chem. 234 (5): 1195–8. PMID 13654346. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
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 (1956). "Ergothioneine in microorganisms". J. Biol. Chem. 223 (1): 9–17. PMID 13376573. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
14. Hand CE, Honek JF (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. {{cite journal}}: Unknown parameter |month= ignored (help)
15. Akanmu D, Cecchini R, Aruoma OI, Halliwell B (1991). "The antioxidant action of ergothioneine". Arch. Biochem. Biophys. 288 (1): 10–6. doi:10.1016/0003-9861(91)90158-F. PMID 1654816. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
16. ^ Misiti F, Castagnola M, Zuppi C, Giardina B, Messana I (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
18. Nakamura T, Yoshida K, Yabuuchi H, Maeda T, Tamai I (2008). "Functional characterization of ergothioneine transport by rat organic cation/carnitine transporter Octn1 (slc22a4)" (– ). Biol. Pharm. Bull. 31 (8): 1580–4. doi:10.1248/bpb.31.1580. PMID 18670092. {{cite journal}}: External link in |format= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
19. Taubert D, Lazar A, Grimberg G; et al. (2006). "Association of rheumatoid arthritis with ergothioneine levels in red blood cells: a case control study". J. Rheumatol. 33 (11): 2139–45. PMID 17086603. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

External links

• Ergothioneine Human Metabolome Database
• Ergothioneine KEGG Compound
• Ergothioneine OXIS INTERNATIONAL
• Ergothioneine TETRAHEDRON

• Thioureas
• Amino acids
• Imidazolines