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Free Radic Biol Med. 2017 Dec;113:385-394. doi: 10.1016/j.freeradbiomed.2017.10.372. Epub 2017 Oct 23.

Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity.

Author information

1
Department of Pharmacology, University of Cologne, Gleueler Straße 24, 50931 Cologne, Germany.
2
Department of Chemistry, University of Cologne, Greinstraße 4, 50939 Cologne, Germany.
3
MS-Platform Biocenter, Cluster of Excellence on Plant Science (CEPLAS), University of Cologne, Zülpicher Straße 47b, 50674 Cologne, Germany.
4
Department of Pharmacology, University of Cologne, Gleueler Straße 24, 50931 Cologne, Germany. Electronic address: dirk.gruendemann@uni-koeln.de.

Abstract

The candidate vitamin ergothioneine (ET), an imidazole-2-thione derivative of histidine betaine, is generally considered an antioxidant. However, the precise physiological role of ET is still unresolved. Here, we investigated in vitro the hypothesis that ET serves specifically to eradicate noxious singlet oxygen (1O2). Pure 1O2 was generated by thermolysis at 37°C of N,N'-di(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide 1,4-endoperoxide (DHPNO2). Assays of DHPNO2 with ET or hercynine (= ET minus sulfur) at pH 7.4 were analyzed by LC-MS in full scan mode to detect products. Based on accurate mass and product ion scan data, several products were identified and then quantitated as a function of time by selected reaction monitoring. All products of hercynine contained, after a [4+2] cycloaddition of 1O2, a carbonyl at position 2 of the imidazole ring. By contrast, because of the doubly bonded sulfur, we infer from the products of ET as the initial intermediates a 4,5-dioxetane (after [2+2] cycloaddition) and hydroperoxides at position 4 and 5 (after Schenck ene reactions). The generation of single products from ET, but not from hercynine, was fully resistant to a large excess of tris(hydroxymethyl)aminomethane (TRIS) or glutathione (GSH). This suggests that 1O2 markedly favors ET over GSH (at least 50-fold) and TRIS (at least 250-fold) for the initial reaction. Loss of ET was almost abolished in 5mM GSH, but not in 25mM TRIS. Regeneration of ET seems feasible, since some ET products - by contrast to hercynine products - decomposed easily in the MS collision cell to become aromatic again.

KEYWORDS:

Antioxidant; Ergothioneine; Glutathione; Hydroperoxide; Imidazole; LC-MS; Singlet oxygen

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