Other ligands, such as nitric oxide and hydrogen sulfide, can also inhibit COX by binding to regulatory sites on the enzyme, reducing the rate of cellular respiration.Cyanide is a non-competitive inhibitor for COX, binding with high affinity to the partially-reduced state of the enzyme and hindering further reduction of the enzyme. In the pulsed state, cyanide binds slowly, but with high affinity. The ligand is posited to electrostatically stabilize both metals at once by positioning itself between them. A high nitric oxide concentration, such as one added exogenously to the enzyme, reverses cyanide inhibition of COX.Nitric oxide can reversibly bind to either metal ion in the binuclear center to be oxidized to nitrite. NO and CN− will compete with oxygen to bind at the site, reducing the rate of cellular respiration. Endogenous NO, however, which is produced at lower levels, augments CN− inhibition. Higher levels of NO, which correlate with the existence of more enzyme in the reduced state, lead to a greater inhibition of cyanide. At these basal concentrations, NO inhibition of Complex IV is known to have beneficial effects, such as increasing oxygen levels in blood vessel tissues. The inability of the enzyme to reduce oxygen to water results in a buildup of oxygen, which can diffuse deeper into surrounding tissues. NO inhibition of Complex IV has a larger effect at lower oxygen concentrations, increasing its utility as a vasodilator in tissues of need.Hydrogen sulfide will bind COX in a noncompetitive fashion at a regulatory site on the enzyme, similar to carbon monoxide.
Such brain mapping has been accomplished in spontaneous mutant mice with cerebellar disease such as reeler and a transgenic model of Alzheimers disease. This technique has also been used to map learning activity in the animal brain. Additional images
See also
Cytochrome c oxidase subunit I
Cytochrome c oxidase subunit II
Cytochrome c oxidase subunit III
Heme a

References
External links
The Cytochrome Oxidase home page at Rice University
Interactive Molecular model of cytochrome c oxidase (Requires MDL Chime)
UMich Orientation of Proteins in Membranes families/superfamily-4
Cytochrome-c+Oxidase at the US National Library of Medicine Medical Subject Headings (MeSH)