Cytochrome c oxidase (COX) (COX)

Cytochrome c oxidase (COX), also known as Complex IV, is the terminal enzyme of the mitochondrial electron transport chain, responsible for the final reduction of molecular oxygen to water [1]. This enzyme complex is vital for aerobic respiration, as it facilitates the translocation of protons across the inner mitochondrial membrane to generate the electrochemical gradient required for ATP synthesis [2]. Cyanide acts as a potent and rapid-acting toxin by binding to the ferric (Fe3+) iron within the heme a3-copper B binuclear center of the enzyme [3]. This binding prevents the reduction of oxygen, effectively halting the electron transport chain and causing "histotoxic hypoxia," where cells cannot utilize oxygen despite its presence in the blood [4]. The resulting failure of oxidative phosphorylation leads to a rapid shift to anaerobic metabolism, causing severe lactic acidosis and organ failure, particularly in the brain and heart [5]. Therapeutic strategies for cyanide poisoning involve the use of antidotes like hydroxocobalamin, which sequesters cyanide, or nitrites, which induce methemoglobinemia to provide alternative binding sites, thereby restoring the catalytic activity of cytochrome c oxidase [6].

Other names

Complex IVCytochrome aa3Ferrocytochrome c: oxygen oxidoreductaseMitochondrial complex IV

Cyanide binds to the ferric (Fe3+) iron in the heme a3-copper B binuclear center of cytochrome c oxidase, inhibiting the final step of the electron transport chain and preventing oxygen utilization.