The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: chemical mechanism and physiological significance

J Bioenerg Biomembr. 2008 Oct;40(5):533-9. doi: 10.1007/s10863-008-9166-6. Epub 2008 Oct 7.


The four gases, nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H(2)S) and hydrogen cyanide (HCN) all readily inhibit oxygen consumption by mitochondrial cytochrome oxidase. This inhibition is responsible for much of their toxicity when they are applied externally to the body. However, recently these gases have all been implicated, to greater or lesser extents, in normal cellular signalling events. In this review we analyse the chemistry of this inhibition, comparing and contrasting mechanism and discussing physiological consequences. The inhibition by NO and CO is dependent on oxygen concentration, but that of HCN and H(2)S is not. NO and H(2)S are readily metabolised by oxidative processes within cytochrome oxidase. In these cases the enzyme may act as a physiological detoxifier of these gases. CO oxidation is much slower and unlikely to be as physiologically important. The evidence for normal physiological levels of these gases interacting with cytochrome oxidase is equivocal, in part because there is little robust data about their steady state concentrations. A reasonable case can be made for NO, and perhaps CO and H(2)S, inhibiting cytochrome oxidase in vivo, but endogenous levels of HCN seem unlikely to be high enough.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carbon Monoxide / metabolism
  • Carbon Monoxide / pharmacology
  • Electron Transport Complex IV / antagonists & inhibitors*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gases / metabolism
  • Gases / pharmacology
  • Humans
  • Hydrogen Cyanide / metabolism
  • Hydrogen Cyanide / pharmacology
  • Hydrogen Sulfide / metabolism
  • Hydrogen Sulfide / pharmacology
  • Hypoxia / enzymology
  • Mitochondria / drug effects*
  • Mitochondria / enzymology*
  • Models, Biological
  • Nitric Oxide / metabolism
  • Nitric Oxide / physiology
  • Signal Transduction / drug effects


  • Enzyme Inhibitors
  • Gases
  • Hydrogen Cyanide
  • Nitric Oxide
  • Carbon Monoxide
  • Electron Transport Complex IV
  • Hydrogen Sulfide