Antagonism of nitric oxide toward the inhibition of cytochrome c oxidase by carbon monoxide and cyanide.
Level 5 - mechanism / opinion, no new human data
In vitro bench study on isolated enzyme and hemoprotein preparations (non-clinical mechanistic research).
PubMed 18956847 · doi:10.1021/tx800140y
What was done
Authors measured the combined inhibitory effects of paired respiratory inhibitors (CO + CN-, NO + CN-, and NO + CO) on the activity of isolated cytochrome c oxidase preparations. They also examined the mechanism and kinetics of ligand displacement of heme-bound CN- by NO in cytochrome c oxidase and hemoglobin.
What was found
The abstract reports no numerical values, concentrations, or kinetic parameters. Qualitatively, the combined inhibition of cytochrome c oxidase by CO and CN- was additive, whereas NO acted antagonistically against both CO and CN-, reducing their inhibitory effects. Displacement of heme-bound CN- by NO appeared to be rate-limited by heme reduction and facilitated by nonligand-binding electron-transfer centers in the enzyme.
Why it matters
Reveals that combined exposures to common respiratory toxins do not always act additively at complex IV, showing that nitric oxide can biochemically attenuate cyanide and carbon monoxide inhibition.
Limits
The study is restricted to isolated in vitro enzyme and hemoprotein preparations; cellular and in vivo metabolic contexts were not evaluated. The abstract provides no quantitative data, concentration-response curves, or statistical variance.
Cited by
- supports Cyanide causes rapid death by binding to proteins involved in aerobic respiration and shutting down oxidative phosphorylation.