Cyanide poisoning causes cytotoxic hypoxia. The mechanism is inhibition of:
- A Complex I (NADH dehydrogenase) of the ETC
- B ATP synthase (Complex V), causing proton backflow
- C Complex IV (cytochrome c oxidase), preventing electron transfer to O2 ✓
- D Cytochrome c, preventing electron shuttling from Complex III to IV
Explanation
Cyanide (CN-) binds the ferric (Fe3+) form of cytochrome a3 in Complex IV (cytochrome c oxidase) with high affinity, preventing the reduction of O2 to H2O; the entire ETC backs up, proton gradient collapses, and OXPHOS ceases. Cells cannot use O2 despite adequate delivery — 'histotoxic hypoxia'. Treatment: hydroxocobalamin chelates CN- or sodium nitrite induces methaemoglobin which competes for CN-. Rotenone inhibits Complex I; oligomycin inhibits Complex V.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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