Antioxidant Functions of Ergothioneine

Abstract

The function of ergothioneine (EGT) has been in controversy since the discovery of EGT in 1909. The present common understanding is that the functions of EGT remain unclear and that EGT does not seem to provide any advantage over other antioxidants. In this study, the ultraviolet-absorption spectra of EGT were measured at various pH. Thermodynamical parameters such as the chemical structure and bond distances of EGT were derived by BMK/6-311+G**. The molecular orbital quantum parameters such as electron distribution, frontier electron density, highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), and singly occupied molecular orbital (SOMO) were derived by HF/STO-3G. The results show that EGT exists as a resonance system mixing of thione state and ionic state in solution not only at physiological pH but also in a wide acidic pH range. EGT is very stable because of the resonance system, whereas the ionic state of EGT forms the metal complexes and the EGT-disulfide in the presence of divalent metal ions. The efficient delocalization of π-electrons on the imidazole ring of EGT increases the HOMO energy level and the rate constant of EGT towards hydroxyl (OH) radical. EGT has a high antioxidant activity by donating the highest active electron on the S atom of the imidazole ring of EGT to OH radical. Because OH radical reacts faster with EGT than any other biomolecules such as proteins and DNA, EGT consequently protects the biomolecules against oxidative damage due to the OH radical.