A mitochondrial Complex I inhibitor (e.g., rotenone) blocks electron transfer from NADH to CoQ (ubiquinone). In the presence of rotenone, which substrates can STILL generate ATP via oxidative phosphorylation?
- A Pyruvate and malate only
- B Succinate and fatty acyl-CoA — as they donate electrons via FADH2 to Complex II or ETF/Q directly ✓
- C No substrate can generate ATP as rotenone blocks the entire ETC
- D Glutamate and alpha-ketoglutarate via direct Complex III entry
Explanation
Rotenone blocks Complex I (NADH:ubiquinone oxidoreductase), specifically preventing NADH from donating electrons to CoQ. However, electrons can bypass Complex I via Complex II (succinate dehydrogenase, which uses FADH2 to directly reduce CoQ) and via electron transfer flavoprotein (ETF) and ETF-QO (fatty acid beta-oxidation donates electrons from FADH2 directly to CoQ). These bypass Complex I entirely, so succinate, fatty acyl-CoA (and glycerol-3-phosphate via mitochondrial G3P dehydrogenase) can still drive ETC via Complexes III, IV and maintain a proton gradient for ATP synthesis. Pyruvate and malate require NAD+-linked enzymes (PDH, malate dehydrogenase) producing NADH — these are blocked by rotenone.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.