Which complex of the electron transport chain is the site of action of cyanide poisoning?

Question

Accepted Answer

A. Complex IV (Cytochrome c oxidase). ## Complex IV and Cyanide Toxicity

### Mechanism of Cyanide Poisoning

**Key Point:** Cyanide binds irreversibly to the ferric iron (Fe³⁺) in cytochrome a₃, the terminal electron acceptor of Complex IV (cytochrome c oxidase), preventing the transfer of electrons to oxygen.

### Why Complex IV?

Complex IV catalyzes the final step of the electron transport chain:

$$2 	ext{Cytochrome } c^{2+} + \frac{1}{2}O_2 + 2H^+ ightarrow 2 	ext{Cytochrome } c^{3+} + H_2O$$

- **Cyanide binding site:** Cytochrome a₃ (heme a₃-Cu binuclear center)
- **Result:** Electrons cannot be transferred to O₂, the ETC halts, and ATP synthesis ceases
- **Cellular consequence:** Rapid aerobic respiration failure; tissues with high energy demand (brain, heart) are affected first

### Why Not Other Complexes?

| Complex | Substrate | Cyanide Sensitivity |
| --- | --- | --- |
| Complex I | NADH | Not affected by cyanide |
| Complex II | Succinate | Not affected by cyanide |
| Complex III | Reduced ubiquinol | Not affected by cyanide |
| Complex IV | Cytochrome c | **Highly sensitive** — terminal oxidase |

**High-Yield:** Cyanide is a classic example of a non-competitive, irreversible inhibitor that specifically targets the final step of aerobic respiration.

**Clinical Pearl:** Cyanide poisoning causes histotoxic hypoxia — tissues cannot use oxygen even though it is available in the blood.

Answer

B. Complex II (Succinate dehydrogenase)

Answer

C. Complex I (NADH dehydrogenase)

Answer

D. Complex III (Cytochrome bc1 complex)

Which complex of the electron transport chain is the site of action of cyanide poisoning?

Explanation

Complex IV and Cyanide Toxicity

Mechanism of Cyanide Poisoning

Why Complex IV?

Why Not Other Complexes?

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Complex	Substrate	Cyanide Sensitivity
Complex I	NADH	Not affected by cyanide
Complex II	Succinate	Not affected by cyanide
Complex III	Reduced ubiquinol	Not affected by cyanide
Complex IV	Cytochrome c	Highly sensitive — terminal oxidase