Rotenone, a pesticide, specifically inhibits Complex I of the ETC. Which metabolic consequence is MOST direct?
- A FADH2 cannot be oxidised, halting beta-oxidation
- B Cytochrome c is not reduced, preventing apoptosis
- C NADH cannot be oxidised, blocking TCA cycle at all NADH-generating steps, halting oxidative phosphorylation, and increasing lactic acidosis ✓
- D ATP synthase (Complex V) is directly inhibited by accumulated protons
Correct answer: C. NADH cannot be oxidised, blocking TCA cycle at all NADH-generating steps, halting oxidative phosphorylation, and increasing lactic acidosis
Explanation
Complex I (NADH:ubiquinone oxidoreductase) accepts electrons from NADH and transfers them to ubiquinone (CoQ), simultaneously pumping protons across the inner mitochondrial membrane. Rotenone blocks this transfer; NADH cannot be reoxidised to NAD+, depleting the NAD+ needed for TCA cycle dehydrogenases (isocitrate, alpha-ketoglutarate, malate dehydrogenases) and pyruvate dehydrogenase. Cells shift to anaerobic glycolysis, causing lactic acidosis. Rotenone is linked to Parkinson-like dopaminergic neurodegeneration.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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