OP48 - The good and bad sides of thiols as one-electron donors in free radical processes

Abstract

Redox reactions of thiols play important roles in many biologic processes including signaling, enzymatic reactions and the defense against reactive oxygen species. These redox reactions proceed via one-electron or two-electron oxidation and reduction processes. Especially the one-electron redox reactions lead to free radical species such as thiyl radicals, and a potential role for thiyl radicals in signaling, the formation of S-nitroso-thiols, and higher oxidation products of thiols has been discussed. However, thiyl radicals are generally quite reactive towards many classes of biomolecules, including polyunsaturated fatty acids, carbohydrates, and proteins. This presentation will focus on deleterious reactions of thiyl radicals, particularly hydrogen transfer reactions within peptides and proteins, which can lead to the generation of a manifold of different products, including electrophiles, D-amino acids, cross-links and fragmentation products. Examples will be provided for glutathione (GSH), GAPDH, SERCA and a number of antibodies. These reactions proceed with some sequence specificity. Rate constants for these hydrogen transfer processes have been derived by NMR spectroscopy, mass spectrometry, and pulse radiolysis, indicating that they can compete against the reaction of thiyl radicals with oxygen, thiols and ascorbate under specific biologic conditions.