## Mechanism of Cyanide Toxicity **Key Point:** Cyanide binds irreversibly to the ferric iron (Fe³⁺) in cytochrome c oxidase (Complex IV) of the electron transport chain, preventing electron transfer and halting aerobic respiration. ### Why Complex IV? Cytochrome c oxidase is the final electron acceptor in the electron transport chain. When cyanide binds to its iron center: 1. Electron transfer is blocked 2. Oxidative phosphorylation ceases 3. ATP production stops immediately 4. Cells shift to anaerobic metabolism (lactic acidosis) 5. Tissues with high oxygen demand (brain, heart) fail first **High-Yield:** The binding is **irreversible** and **extremely rapid** — even small doses can be lethal because the enzyme is completely inhibited. ### Cellular Consequence | Effect | Mechanism | |--------|----------| | Histotoxic hypoxia | Cells cannot use oxygen despite adequate supply | | Lactic acidosis | Shift to anaerobic glycolysis | | Rapid onset | Brain and heart affected within seconds | | Seizures | Neuronal energy failure | **Clinical Pearl:** This is why cyanide poisoning causes "histotoxic hypoxia" — the problem is not oxygen delivery to tissues, but the inability of cells to use it. Oxygen saturation and blood gases may appear normal, but the patient is dying. **Mnemonic:** **CYANIDE = Cytochrome oxidase Inhibitor** — remember that it targets the final step of the electron transport chain.
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