Cyanide inhibition and pyruvate-induced recovery of cytochrome c oxidase
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Liver metabolism MeSH
- Rats MeSH
- Potassium Cyanide pharmacology MeSH
- Pyruvic Acid metabolism MeSH
- Oxygen metabolism MeSH
- Membrane Potential, Mitochondrial physiology MeSH
- Mitochondria metabolism MeSH
- Rats, Wistar MeSH
- Protons * MeSH
- Electron Transport Complex IV antagonists & inhibitors metabolism MeSH
- Oxygen Consumption physiology MeSH
- Electron Transport physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Potassium Cyanide MeSH
- Pyruvic Acid MeSH
- Oxygen MeSH
- Protons * MeSH
- Electron Transport Complex IV MeSH
The mechanism of cyanide's inhibitory effect on the mitochondrial cytochrome c oxidase (COX) as well as the conditions for its recovery have not yet been fully explained. We investigated three parameters of COX function, namely electron transport (oxygen consumption), proton transport (mitochondrial membrane potential Δψ(m)) and the enzyme affinity to oxygen (p₅₀ value) with regard to the inhibition by KCN and its reversal by pyruvate. 250 μM KCN completely inhibited both the electron and proton transport function of COX. The inhibition was reversible as demonstrated by washing of mitochondria. The addition of 60 mM pyruvate induced the maximal recovery of both parameters to 60-80% of the original values. When using low KCN concentrations of up to 5 μM, we observed a profound, 30-fold decrease of COX affinity for oxygen. Again, this decrease was completely reversed by washing mitochondria while pyruvate induced only a partial, yet significant recovery of oxygen affinity. Our results demonstrate that the inhibition of COX by cyanide is reversible and that the potential of pyruvate as a cyanide poisoning antidote is limited. Importantly, we also showed that the COX affinity for oxygen is the most sensitive indicator of cyanide toxic effects.
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