The fourth electron from another cytochrome c flows through CuA and cytochrome a to the cytochrome a3–CuB binuclear center, reducing the Fe4+=O to Fe3+, with the oxygen atom picking up a proton simultaneously, regenerating this oxygen as a hydroxide ion coordinated in the middle of the cytochrome a3–CuB center as it was at the start of this cycle. Overall, four reduced cytochrome cs are oxidized while O2 and four protons are reduced to two water molecules. : 841–5

Inhibition
COX exists in three conformational states: fully oxidized (pulsed), partially reduced, and fully reduced. Each inhibitor has a high affinity to a different state. In the pulsed state, both the heme a3 and the CuB nuclear centers are oxidized; this is the conformation of the enzyme that has the highest activity. A two-electron reduction initiates a conformational change that allows oxygen to bind at the active site to the partially-reduced enzyme. Four electrons bind to COX to fully reduce the enzyme. Its fully reduced state, which consists of a reduced Fe2+ at the cytochrome a3 heme group and a reduced CuB+ binuclear center, is considered the inactive or resting state of the enzyme.Cyanide, azide, and carbon monoxide all bind to cytochrome c oxidase, inhibiting the protein from functioning and leading to the chemical asphyxiation of cells. Higher concentrations of molecular oxygen are needed to compensate for increasing inhibitor concentrations, leading to an overall reduction in metabolic activity in the cell in the presence of an inhibitor.
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)