L-Ergothioneine; (+)-Ergothioneine; Thiasine; Sympectothion; Ergothionine; Erythrothioneine; Thiolhistidinebetaine
|Molar mass||229.30 g/mol|
|Melting point||275 to 277 °C (527 to 531 °F; 548 to 550 K)|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is: / ?)(|
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. 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.
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. 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, kidney bean 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 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. The biosynthetic genes of ergothioneine have been described in Mycobacterium smegmatis, Neurospora crassa, and Schizosaccharomyces pombe.
Ergothioneine has antioxidant properties in vitro. Under laboratory conditions, it scavenges hydroxyl radicals and hypochlorous acid, inhibits production of oxidants by metal ions, and may participate in metal ion transport and regulation of metalloenzymes. As these properties were measured in cell-free systems, their relevance to actual function of ergothioneine in vivo remains unproven.
In vitro, 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. One human study showed pain reduction and increased range of movement over six weeks of dietary supplementation.
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