Universität zu Köln

Oumari, Mhmd, Goldfuss, Bernd ORCID: 0000-0002-1814-8818, Stoffels, Christopher, Schmalz, Hans-Guenther and Gruendemann, Dirk (2019). Regeneration of ergothioneine after reaction with singlet oxygen. Free Radic. Biol. Med., 134. S. 508 - 515. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1873-4596

Full text not available from this repository.

Abstract

Ergothioneine (ET), an imidazole-2-thione derivative of histidine betaine, is generally considered an antioxidant. Important antioxidants are typically regenerated from their oxidized products, to prevent the interceptors from being lost after a single chemical reaction with a reactive oxygen species. However, no mechanism for the complete regeneration of ET has yet been uncovered. Here we define a non-enzymatic multi-step cycle for the regeneration of ET after reaction with singlet oxygen (O-1(2)). All reaction steps were verified by density functional theory computations. Four molecules of GSH are used per turn to detoxify O-1(2) to water. Pure O-1(2) was generated by thermolysis at 37 degrees C of the endoperoxide DHPNO2. Addition of 1 mM ET to 10 mM DHPNO2 and 10 mM GSH increased the production of oxidized GSH (GSSG), measured by LC-MS/MS, by a factor of 26 (water) and 28 (D2O), respectively. In the same assay, the ring of ET alone was able to drive the cycle at equal speed; thus, the zwitterionic amino acid backbone was not involved. Our data suggest that ET reacts at least 4-fold faster with O-1(2) than ascorbic acid. ET must now be viewed as tightly linked with the GSH/GSSG redox couple. The necessary thiol foundation is present in all mammalian and vertebrate cells, and also in all species that generate ET, such as cyanobacteria, mycobacteria, and fungi. Regeneration provides a decisive advantage for ET over other reactive, but non-recoverable, compounds. Our findings substantiate the importance of ET for the eradication of noxious O-1(2).

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Oumari, Mhmd UNSPECIFIED UNSPECIFIED UNSPECIFIED Goldfuss, Bernd UNSPECIFIED orcid.org/0000-0002-1814-8818 UNSPECIFIED Stoffels, Christopher UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmalz, Hans-Guenther UNSPECIFIED UNSPECIFIED UNSPECIFIED Gruendemann, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-151339
DOI:	10.1016/j.freeradbiomed.2019.01.043
Journal or Publication Title:	Free Radic. Biol. Med.
Volume:	134
Page Range:	S. 508 - 515
Date:	2019
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1873-4596
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Organic Chemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MOLECULAR-OXYGEN; TRANSPORTER; GLUTATHIONE; CYANOBACTERIA; BIOSYNTHESIS; ASCORBATE; HERCYNINE; THIOLS; ACID; TOOL Multiple languages Biochemistry & Molecular Biology; Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15133