Rotenone (used as a pesticide) specifically inhibits complex I of the electron transport chain. A patient with rotenone poisoning would show which metabolic consequence?

• A Accumulation of NADH with impaired NADH oxidation, lactic acidosis from impaired pyruvate dehydrogenase activity, and severely reduced ATP synthesis ✓
• B Accumulation of FADH2, NADH, and succinate with normal ATP synthesis as complex II is unaffected
• C Selective accumulation of succinate only, because complex I inhibition shunts electrons entirely through complex II
• D Uncoupling of oxidative phosphorylation with heat generation, as electrons bypass complex I directly to cytochrome c

Explanation

Complex I (NADH-ubiquinone oxidoreductase) oxidises NADH from the TCA cycle and beta-oxidation, transferring electrons to coenzyme Q. Its inhibition causes NADH accumulation, which inhibits all NADH-generating dehydrogenases (isocitrate dehydrogenase, alpha-KGDH, malate dehydrogenase) and pyruvate dehydrogenase. This results in pyruvate accumulation → lactate (lactic acidosis). ATP synthesis is severely impaired because Complex I handles about 40% of electron flow in active mitochondria. Rotenone is mechanistically similar to MPTP-induced parkinsonism (MPTP→MPP⁺ inhibits complex I in substantia nigra neurons).

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.