Rotenone is a complex I inhibitor of the ETC. Which substrate can bypass the rotenone block and maintain mitochondrial NADH-independent electron flow into the ETC?

• A Succinate, donating electrons via FADH2 to Complex II (ubiquinone reductase) ✓
• B Malate, generating NADH via malate dehydrogenase for Complex I
• C Pyruvate, entering the TCA cycle via PDH and generating NADH
• D Glutamate, via transamination generating NADH through the malate-aspartate shuttle

Explanation

Rotenone (like amytal/barbiturates) blocks Complex I (NADH:ubiquinone oxidoreductase), preventing NADH-derived electrons from entering the ETC. Succinate is oxidised by succinate dehydrogenase (Complex II), generating FADH2 within Complex II, which directly reduces coenzyme Q (ubiquinone) without involving Complex I. Electrons thus enter the ETC at CoQ and proceed through Complex III → cytochrome c → Complex IV to oxygen, generating a proton gradient for ATP synthesis. Malate, pyruvate and glutamate all ultimately generate NADH, which requires Complex I for electron entry and would also be 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.