Editing Cytochrome c oxidase (section)

== Biochemistry ==
{{missing information|section|names of the six traditional intermediate states (APFOER); 2021 Cyro-EM result proposing an RPFOE mechanism with reversed assignment of red-ox phases ({{doi|10.1038/s41467-021-27174-y}} {{open access}})|date=December 2021}}
The overall reaction is
: 4 Fe{{sup|2+}} – cytochrome ''c'' + 4 H{{sup|+}} + O{{sub|2}} → 4 Fe{{sup|3+}} – cytochrome ''c'' + 2 H{{sub|2}}O                Δ''G''{{sup|o}}' = - 218 kJ/mol,  ''E''{{sup|o}}' = +565 mV

Two electrons are passed from two cytochrome c's, through the Cu{{sub|A}} and cytochrome a sites to the cytochrome a{{sub|3}}–Cu{{sub|B}} binuclear center, reducing the metals to the Fe{{sup|2+}} form and Cu{{sup|+}}. The hydroxide ligand is protonated and lost as water, creating a void between the metals that is filled by O{{sub|2}}. The oxygen is rapidly reduced, with two electrons coming from the Fe{{sup|2+}}-cytochrome a{{sub|3}}, which is converted to the ferryl oxo form (Fe{{sup|4+}}=O). The oxygen atom close to Cu{{sub|B}} picks up one electron from Cu{{sup|+}}, and a second electron and a proton from the [[hydroxyl]] of Tyr(244), which becomes a tyrosyl radical. The second oxygen is converted to a hydroxide ion by picking up two electrons and a proton. A third electron from another cytochrome c is passed through the first two electron carriers to the cytochrome a{{sub|3}}–Cu{{sub|B}} binuclear center, and this electron and two protons convert the tyrosyl radical back to Tyr, and the hydroxide bound to Cu{{sub|B}}{{sup|2+}} to a water molecule. The fourth electron from another cytochrome c flows through Cu{{sub|A}} and cytochrome a to the cytochrome a{{sub|3}}–Cu{{sub|B}} binuclear center, reducing the Fe{{sup|4+}}=O to Fe{{sup|3+}}, with the oxygen atom picking up a proton simultaneously, regenerating this oxygen as a hydroxide ion coordinated in the middle of the cytochrome a{{sub|3}}–Cu{{sub|B}} center as it was at the start of this cycle. Overall, four reduced cytochrome c's are oxidized while O{{sub|2}} and four protons are reduced to two water molecules.<ref name = "Voest_2011">{{cite book |last1=Voet |first1=Donald |last2=Voet |first2=Judith G.  | name-list-style = vanc |title=Biochemistry |date=2011 |publisher=John Wiley & Sons |location=Hoboken, NJ |isbn=978-0-470-57095-1 |edition=4th}}</ref>{{rp|841–5}}