## Mechanism of Cyanide Toxicity **Key Point:** Cyanide binds irreversibly to the ferric iron (Fe³⁺) in cytochrome c oxidase (Complex IV), the terminal enzyme of the electron transport chain, blocking electron transfer to oxygen. ### Why Complex IV? Cyanide's high affinity for the Fe³⁺ form of cytochrome a₃ (the catalytic center of Complex IV) prevents the final step of aerobic respiration: $$\text{Cytochrome a}_3^{3+} + \text{CN}^- \rightarrow \text{Cytochrome a}_3^{3+}\text{-CN}^-$$ This halts: - Electron transport - Oxidative phosphorylation - ATP production - Aerobic metabolism ### Cellular Consequence Cells switch to anaerobic metabolism, producing lactic acid and leading to: - Metabolic acidosis - Tissue hypoxia (despite normal oxygen saturation) - Rapid death of high-energy organs (brain, heart) **High-Yield:** Cyanide poisoning causes **histotoxic hypoxia** — oxygen is available but cells cannot use it. This is why pulse oximetry and arterial oxygen levels may appear normal, but the patient is dying. **Clinical Pearl:** The classic presentation includes altered mental status, cardiac arrhythmias, and rapid cardiovascular collapse within minutes of exposure.
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