title: Protein thiyl radical reactions and product formation: a kinetic simulation.
abstract: Protein thiyl radicals are important intermediates generated in redox processes of thiols and disulfides. Thiyl radicals efficiently react with glutathione and ascorbate, and the common notion is that these reactions serve to eliminate thiyl radicals before they can enter potentially hazardous processes. However, over the past years increasing evidence has been provided for rather efficient intramolecular hydrogen transfer processes of thiyl radicals in proteins and peptides. Based on rate constants published for these processes, we have performed kinetic simulations of protein thiyl radical reactivity. Our simulations suggest that protein thiyl radicals enter intramolecular hydrogen transfer reactions to a significant extent even under physiologic conditions, i.e., in the presence of 30 µM oxygen, 1 mM ascorbate, and 10 mM glutathione. At lower concentrations of ascorbate and glutathione, frequently observed when tissue is exposed to oxidative stress, the extent of irreversible protein thiyl radical-dependent protein modification increases.
authors.affiliation: Institute of Inorganic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland. Electronic address: nauser@inorg.chem.ethz.ch.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nauser
authors.affiliation: Institute of Inorganic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Willem H
authors.initials: WH
authors.lastname: Koppenol
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66047, USA. Electronic address: schoneic@ku.edu.
authors.forename: Christian
authors.initials: C
authors.lastname: Schöneich
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry* / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D004220:Disulfides; D005609:Free Radicals; D011506:Proteins; D013438:Sulfhydryl Compounds; D006859:Hydrogen; D005978:Glutathione; D001205:Ascorbic Acid; D010100:Oxygen
keywords: Carbon-centered radicals; D-Amino acids; Free radicals; Glutathione; Hydrogen atom transfer; Thiyl radicals