Q.32 Cyanide poisoning is due to its direct inhibition of
Options:
(A) Electron transport chain
(B) Fatty acid biosynthesis
(C) Fatty acid oxidation
(D) Nucleic acid biosynthesis
Cyanide (CN⁻) represents the classic mitochondrial poison, causing rapid death through cellular energy failure. Its lethality stems from binding the heme a3-CuB center of Complex IV (cytochrome c oxidase), preventing electron transfer to O₂ and halting ATP production via oxidative phosphorylation.
The correct answer is (A) Electron transport chain, specifically irreversible inhibition of Complex IV, blocking ~90% of cellular ATP generation.
Why (A) Electron Transport Chain is Cyanide’s Direct Target
Cyanide coordinates Fe³⁺ in cytochrome c oxidase’s heme group, creating a stable Fe³⁺-CN complex. This prevents O₂ binding, stopping electron flow from cyt c → O₂. Result: stalled proton pumping, collapsed proton motive force, halted ATP synthase. Cells shift to anaerobic glycolysis (lactate acidosis), but brain/heart fail within minutes due to ATP depletion.
Explanation of All Options
Each represents major metabolic pathways cyanide doesn’t directly target:
-
(A) Electron transport chain
Correct. CN⁻ binds Complex IV heme iron, blocking electron transfer to O₂. Primary cause of histotoxic hypoxia. -
(B) Fatty acid biosynthesis
Wrong. Requires NADPH (not directly ETC-dependent). Cyanide doesn’t inhibit acetyl-CoA carboxylase or FAS I/II. -
(C) Fatty acid oxidation
Incorrect. β-oxidation generates FADH₂/NADH for ETC. Cyanide blocks ETC utilization of these reducing equivalents, but doesn’t directly inhibit acyl-CoA dehydrogenase/carnitine systems. -
(D) Nucleic acid biosynthesis
No. DNA/RNA synthesis requires NTPs, ribose-5P. Cyanide doesn’t target polymerases, ribonucleotide reductase, or thymidylate synthase.
Quick Metabolic Target Analysis
| Option | Pathway | Cyanide Direct Inhibition? | Actual Effect |
|---|---|---|---|
| A | Electron transport chain | Yes (Complex IV) | ATP production halted |
| B | Fatty acid biosynthesis | No | Indirect (NADPH depletion) |
| C | Fatty acid oxidation | No | Substrate accumulates |
| D | Nucleic acid biosynthesis | No | Indirect (NTP depletion) |
Biotech relevance: Cyanide sensitivity assays measure Complex IV activity in mitochondrial disease diagnostics. Hydroxocobalamin antidotes via CN⁻ → cyanocobalamin detoxification. Memory trick: “CN⁻ = Cytochrome Nails shut Complex IV.”
