Biologically relevant mechanism for catalytic superoxide removal by simple manganese compounds

Nonenzymatic manganese was first shown to provide protection against superoxide toxicity in vivo in 1981, but the chemical mechanism responsible for this protection subsequently became controversial due to conflicting reports concerning the ability of Mn to catalyze superoxide disproportionation in...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-05, Vol.109 (18), p.6892-6897
Main Authors: Barnese, Kevin, Gralla, Edith Butler, Valentine, Joan Selverstone, Cabelli, Diane E.
Format: Article
Language:English
Subjects:
Antioxidants - metabolism
Antioxidants - pharmacology
Biological Sciences
Carbonates
Carbonates - metabolism
Carbonates - pharmacology
Catalysis
Chemical reactions
Citrates
Ethanol
In Vitro Techniques
Kinetics
Ligands
Manganese
Manganese - metabolism
Manganese - pharmacology
Manganese compounds
Models, Biological
Organometallic Compounds - metabolism
Organometallic Compounds - pharmacology
Oxidative Stress - drug effects
Phosphates
Physical Sciences
Radiolysis
Superoxide Dismutase - metabolism
Superoxides
Superoxides - antagonists & inhibitors
Superoxides - metabolism
Toxicity
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Summary:Nonenzymatic manganese was first shown to provide protection against superoxide toxicity in vivo in 1981, but the chemical mechanism responsible for this protection subsequently became controversial due to conflicting reports concerning the ability of Mn to catalyze superoxide disproportionation in vitro. In a recent communication, we reported that low concentrations of a simple Mn phosphate salt under physiologically relevant conditions will indeed catalyze superoxide disproportionation in vitro. We report now that two of the four Mn complexes that are expected to be most abundant in vivo, Mn phosphate and Mn carbonate, can catalyze superoxide disproportionation at physiologically relevant concentrations and pH, whereas Mn pyrophosphate and citrate complexes cannot. Additionally, the chemical mechanisms of these reactions have been studied in detail, and the rates of reactions of the catalytic removal of superoxide by Mn phosphate and carbonate have been modeled. Physiologically relevant concentrations of these compounds were found to be sufficient to mimic an effective concentration of enzymatic superoxide dismutase found in vivo. This mechanism provides a likely explanation as to how Mn combats superoxide stress in cellular systems.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1203051109