title: Transition metals as catalysts of "autoxidation" reactions.
abstract: Superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (.OH) produced from the "autoxidation" of biomolecules, such as ascorbate, catecholamines, or thiols, have been implicated in numerous toxicities. However, the direct reaction of dioxygen with the vast majority of biomolecules, including those listed above, is spin forbidden, a condition which imposes a severe kinetic limitation on this reaction pathway. Therefore, an alternate mechanism must be invoked to explain the "autoxidations" reactions frequently reported. Transition metals are efficient catalysts of redox reactions and their reactions with dioxygen are not spin restricted. Therefore it is likely that the "autoxidation" observed for many biomolecules is, in fact, metal catalyzed. In this paper we discuss: 1) the quantum mechanic, thermodynamic, and kinetic aspects of the reactions of dioxygen with biomolecules; 2) the involvement of transition metals in biomolecule oxidation; and 3) the biological implications of metal catalyzed oxidations. We hypothesize that true autoxidation of biomolecules does not occur in biological systems, instead the "autoxidation" of biomolecules is the result of transition metals bound by the biomolecules.
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, Logan 84322-0300.
authors.forename: D M
authors.initials: DM
authors.lastname: Miller
authors.forename: G R
authors.initials: GR
authors.lastname: Buettner
authors.forename: S D
authors.initials: SD
authors.lastname: Aust
mesh_terms: D000818:Animals; D002384:Catalysis; D002614:Chelating Agents; D003300:Copper / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D007501:Iron / Q000378:metabolism; D008670:Metals / Q000378:metabolism* / Q000633:toxicity; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D002614:Chelating Agents; D005609:Free Radicals; D008670:Metals; D003300:Copper; D007501:Iron; D010100:Oxygen