## Mechanism of Cyanide Toxicity **Key Point:** Cyanide binds irreversibly to the ferric iron (Fe³⁺) of cytochrome c oxidase (Complex IV) in the inner mitochondrial membrane, blocking the final step of the electron transport chain. ### Why Complex IV? Cytochrome c oxidase catalyzes the transfer of electrons to oxygen, the final electron acceptor in aerobic respiration. When cyanide binds to the heme a₃ iron center, electron transport halts, ATP production ceases, and cells switch to anaerobic metabolism. ### Cellular Consequences 1. Immediate cessation of oxidative phosphorylation 2. Rapid depletion of ATP 3. Shift to anaerobic glycolysis → lactic acidosis 4. Tissues with high oxygen demand (brain, heart) fail first **High-Yield:** Cyanide poisoning causes **histotoxic hypoxia** — oxygen is available in blood, but cells cannot use it. This is why PaO₂ remains normal but arteriovenous O₂ difference is minimal. **Clinical Pearl:** The pink or cherry-red discoloration of skin in cyanide poisoning occurs because venous blood remains oxygenated (oxygen cannot be extracted by tissues).
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