ergothioneine

Ergothioneine has been found in bacteria, plants, and animals, sometimes at millimolar levels.{{cite journal | vauthors = Ey J, Schömig E, Taubert D | title = Dietary sources and antioxidant effects of ergothioneine | journal = Journal of Agricultural and Food Chemistry | volume = 55 | issue = 16 | pages = 6466–74 | date = August 2007 | pmid = 17616140 | doi = 10.1021/jf071328f }} Foods found to contain ergothioneine include liver, kidney, black beans, kidney bean, and oat bran, with the highest levels in bolete and oyster mushrooms.Kalač P. Edible Mushrooms. Chapter 4 - Health-Stimulating Compounds and Effects. pp 137-153. Academic Press, 2016. {{isbn|9780128044551}} {{doi|10.1016/B978-0-12-804455-1.00004-7}} 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, semen,{{cite journal | vauthors = Mann T, Leone E | title = Studies on the metabolism of semen. VIII. Ergothioneine as a normal constituent of boar seminal plasma; purification and crystallization; site of formation and function | journal = The Biochemical Journal | volume = 53 | issue = 1 | pages = 140–8 | date = January 1953 | pmid = 13032046 | pmc = 1198115 | doi = 10.1042/bj0530140 }} and skin.{{cite journal | vauthors = Markova NG, Karaman-Jurukovska N, Dong KK, Damaghi N, Smiles KA, Yarosh DB | title = Skin cells and tissue are capable of using L-ergothioneine as an integral component of their antioxidant defense system | journal = Free Radical Biology & Medicine | volume = 46 | issue = 8 | pages = 1168–76 | date = April 2009 | pmid = 19439218 | doi = 10.1016/j.freeradbiomed.2009.01.021 }}

Although many species contain ergothioneine, only a few make it; the others absorb it from their diet or, in the case of plants, from their environment.{{Cite journal | title = The uptake of ergothioneine from the soil into the latex of Hevea brasiliensis | year = 1968 | journal = Phytochemistry | pages = 1999–2000 | volume = 7 | vauthors = Audley BS, Tan CH | doi = 10.1016/S0031-9422(00)90759-3 | issue = 11| bibcode = 1968PChem...7.1999A }} Biosynthesis has been detected in Actinomycetota, such as Mycobacterium smegmatis and certain fungi, such as Neurospora crassa.

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.{{cite journal | vauthors = Melville DB, Ludwig ML, Inamine E, Rachele JR | title = Transmethylation in the biosynthesis of ergothionelne | journal = The Journal of Biological Chemistry | volume = 234 | issue = 5 | pages = 1195–8 | date = May 1959 | doi = 10.1016/S0021-9258(18)98157-3 | pmid = 13654346 | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=13654346 | doi-access = free }}{{Dead link|date=March 2022 |bot=InternetArchiveBot |fix-attempted=yes }} The biosynthetic genes of ergothioneine have been described in Mycobacterium smegmatis,{{cite journal | vauthors = Seebeck FP | title = In vitro reconstitution of Mycobacterial ergothioneine biosynthesis | journal = Journal of the American Chemical Society | volume = 132 | issue = 19 | pages = 6632–3 | date = May 2010 | pmid = 20420449 | doi = 10.1021/ja101721e }} Neurospora crassa,{{cite journal | vauthors = Bello MH, Barrera-Perez V, Morin D, Epstein L | title = 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 | journal = Fungal Genetics and Biology | volume = 49 | issue = 2 | pages = 160–72 | date = February 2012 | pmid = 22209968 | doi = 10.1016/j.fgb.2011.12.007 }} and Schizosaccharomyces pombe.{{cite journal | vauthors = Pluskal T, Ueno M, Yanagida M | title = Genetic and metabolomic dissection of the ergothioneine and selenoneine biosynthetic pathway in the fission yeast, S. pombe, and construction of an overproduction system | journal = PLOS ONE | volume = 9 | issue = 5 | pages = e97774 | year = 2014 | pmid = 24828577 | pmc = 4020840 | doi = 10.1371/journal.pone.0097774 | bibcode = 2014PLoSO...997774P | doi-access = free }}

Other species of bacteria, such as Bacillus subtilis, Escherichia coli, Proteus vulgaris, and Streptococcus, as well as fungi in the Saccharomycotina cannot make ergothioneine.{{cite journal | vauthors = Genghof DS | title = Biosynthesis of ergothioneine and hercynine by fungi and Actinomycetales | journal = Journal of Bacteriology | volume = 103 | issue = 2 | pages = 475–8 | date = August 1970 | pmid = 5432011 | pmc = 248105 | doi = 10.1128/JB.103.2.475-478.1970 }}{{cite journal | vauthors = Genghof DS, Inamine E, Kovalenko V, Melville DB | title = Ergothioneine in microorganisms | journal = The Journal of Biological Chemistry | volume = 223 | issue = 1 | pages = 9–17 | date = November 1956 | doi = 10.1016/S0021-9258(18)65113-0 | pmid = 13376573 | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=13376573 | doi-access = free }}{{Dead link|date=March 2022 |bot=InternetArchiveBot |fix-attempted=yes }}

Ergothioneine is a thiourea derivative of the betaine of histidine and contains a sulfur atom bonded to the 2-position of the imidazole ring.{{cite book|author = Hartman PE| title=Oxygen Radicals in Biological Systems Part B: Oxygen Radicals and Antioxidants | chapter=[32] Ergothioneine as antioxidant |series = Methods in Enzymology |volume = 186|pages = [https://archive.org/details/oxygenradicalsin0000unse/page/310 310–8]|year = 1990|pmid = 2172707|doi = 10.1016/0076-6879(90)86124-E |isbn = 978-0-12-182087-9|chapter-url = https://archive.org/details/oxygenradicalsin0000unse/page/310}} Typical of thioureas, ergothioneine is less reactive than typical thiols such as glutathione towards alkylating agents like maleimides. It also resists oxidation by air. However, ergothioneine can be slowly oxidized over several days to the disulfide form in acidic solutions.{{cite journal | vauthors = Heath H, Toennies G | title = The preparation and properties of ergothioneine disulphide | journal = The Biochemical Journal | volume = 68 | issue = 2 | pages = 204–10 | date = February 1958 | pmid = 13522601 | pmc = 1200325 | doi = 10.1042/bj0680204 }}

Various derivatives of ergothioneine have been reported in the literature, such as S-methyl-ergothioneine{{cite journal | vauthors = Asmus KD, Bensasson RV, Bernier JL, Houssin R, Land EJ | title = One-electron oxidation of ergothioneine and analogues investigated by pulse radiolysis: redox reaction involving ergothioneine and vitamin C | journal = The Biochemical Journal | volume = 315 | issue = 2 | pages = 625–9 | date = April 1996 | pmid = 8615839 | pmc = 1217242 | doi = 10.1042/bj3150625 }} or selenium-containing selenoneine.{{cite journal | vauthors = Yamashita Y, Yamashita M | title = Identification of a novel selenium-containing compound, selenoneine, as the predominant chemical form of organic selenium in the blood of bluefin tuna | journal = The Journal of Biological Chemistry | volume = 285 | issue = 24 | pages = 18134–8 | date = June 2010 | pmid = 20388714 | pmc = 2881734 | doi = 10.1074/jbc.C110.106377 | doi-access = free }}

• Adaptogenic Antioxidant: Ergothioneine is an adaptogenic antioxidant that preferentially accumulates in cells and tissues exposed to oxidative stress and damage. The organic cation transporter OCTN1 (now known as SLC22A4, a transporter protein with 551 amino acids and three glycosylation sites) in the human body can transport ergothioneine to where it is needed.{{Cite journal |last=Halliwell |first=Barry |last2=Cheah |first2=Irwin K. |last3=Tang |first3=Richard M. Y. |date=October 2018 |title=Ergothioneine – a diet‐derived antioxidant with therapeutic potential |url=https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.13123 |journal=FEBS Letters |language=en |volume=592 |issue=20 |pages=3357–3366 |doi=10.1002/1873-3468.13123 |issn=0014-5793}}
• Regenerative Pathway: The human body has a regenerative pathway for ergothioneine. When ergothioneine combines with glutathione, it can regenerate, allowing it to react with singlet oxygen in a cyclical manner, achieving a more comprehensive and lasting antioxidant effect.
• Slow Excretion: Ergothioneine is excreted very slowly in the body, allowing it to be highly retained in the tissues and red blood cells of humans and other animals, thereby maximizing its effectiveness.
• Stable Form: Ergothioneine mainly exists in the form of thione, which has ideal thermal stability and pH stability.

Although potential effects of ergothioneine are under preliminary research, its physiological role in vivo has not been determined.

The Panel on Dietetic Products for the European Food Safety Authority reported safe daily limits of 2.82 mg/kg of body weight for infants, 3.39 mg/kg for small children, and 1.31 mg/kg for adults, including pregnant and breastfeeding women.{{cite journal | vauthors = Turck D, Bresson JL, Burlingame B, Dean T, Fairweather-Tait S, Heinonen M, Hirsch-Ernst KI, Mangelsdorf I, McArdle HJ, Naska A, Neuhäuser-Berthold M, Nowicka G, Pentieva K, Sanz Y, Siani A, Sjödin A, Stern M, Tomé D, Vinceti M, Willatts P, Engel KH, Marchelli R, Pöting A, Poulsen M, Schlatter JR, Ackerl R, van Loveren H | display-authors = 6 | title = Statement on the safety of synthetic l-ergothioneine as a novel food - supplementary dietary exposure and safety assessment for infants and young children, pregnant and breastfeeding women | journal = EFSA Journal | volume = 15 | issue = 11 | pages = e05060 | date = November 2017 | pmid = 32625352 | doi = 10.2903/j.efsa.2017.5060 | pmc = 7010164 | doi-access = free }}

• Oxidative stress
• Reactive oxygen species
• Ovothiol

{{Reflist}}

• [http://www.hmdb.ca/metabolites/HMDB03045 Ergothioneine] Human Metabolome Database
• [http://www.genome.jp/dbget-bin/www_bget?compound+C05570 Ergothioneine] KEGG Compound

Category:Thioureas

Category:Alpha-Amino acids

Category:Imidazolines