Dokument: Non-enzymatic regeneration of ergothioneine after reaction with singlet oxygen
| Titel: | Non-enzymatic regeneration of ergothioneine after reaction with singlet oxygen | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=51025 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20191004-083422-8 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | M.Sc. Oumari, Mhmd [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Proksch, Peter [Gutachter] Prof. Dr. Gründemann, Dirk [Gutachter] | |||||||
| Stichwörter: | Ergothioneine, Glutathione, Ascorbic acid, Singlet oxygen, DHPNO2 | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | Ergothioneine (ET) is a histidine betaine derivative with a sulfur atom attached to the position two of the imidazole ring. As established, ET eradicates singlet oxygen (1O2) and has been considered an antioxidant. Various functions of ET regarding reactive oxygen species (ROS) have been proposed and much progress concerning ET has been attained. However, no mechanism for the regeneration of ET after a reaction with ROS has been determined. In fact, if ET is an important antioxidant, like ascorbate, glutathione (GSH), ubiquinol and vitamin E, and if the benefit of ET in living organisms is continual and does not lose its capacity to eradicate oxidants after a single chemical reaction, then the ET should be regenerated from its oxidized product so as to be an efficient antioxidant. In this work, a non-enzymatic mechanism for the regeneration of ET after reaction with 1O2 was discovered. For this mechanism, four molecules of GSH are needed to detoxify 1O2 into water and oxidized GSH (GSSG) as a by-product. Clean 1O2 was generated by thermolysis at 37 °C of the endoperoxide DHPNO2. Addition of 1 mM ET to 10 mM DHPNO2 and 10 mM GSH increased the production of GSSG by factor of 26 (in water) and 28 (D2O), respectively, measured by means of LC-MS/MS. The ring of ET was responsible for the whole reaction cycle and the zwitterionic amino acid backbone was not involved, since only the ring of ET, and 4-methyl ET ring significantly generated GSSG, with equally high intensity as ET. According to the results from the production of GSSG in the present work, the data suggest that ET reacts with 1O2 150-fold more efficiently than GSH, and ET reacts at least 4-fold faster than ascorbic acid towards 1O2. The necessary thiol foundation (GSH) exists naturally in all mammalian and vertebrate cells as well as in all species that produce ET, such as cyanobacteria, mycobacteria, and fungi with relatively high intracellular concentrations (5 - 10 mM). The byproduct GSSG, regenerates to GSH in living organisms by glutathione reductase, utilizing a NADPH dependent-enzyme. Based on that, ET must now be viewed as closely linked with the redox couple GSH/GSSG. These findings prove the importance of ET over other reactive compounds, that are non-recoverable, for the detoxification of noxious 1O2. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Pharmazie | |||||||
| Dokument erstellt am: | 04.10.2019 | |||||||
| Dateien geändert am: | 04.10.2019 | |||||||
| Promotionsantrag am: | 08.07.2019 | |||||||
| Datum der Promotion: | 18.09.2019 |
