The P/O ratio describes ATP molecules synthesized per oxygen atom reduced. For NADH-linked substrates (feeding Complex I), the theoretical P/O ratio is approximately 2.5, while FADH2-linked substrates (entering at Complex II) have a P/O ratio of approximately 1.5. This difference reflects:
- A FADH2 donating electrons at a higher redox potential than NADH, producing more ATP
- B NADH requiring more oxygen per electron pair than FADH2
- C Complex I pumping 4 protons/2e- versus FADH2 bypassing Complex I and losing those 4 protons from the gradient ✓
- D ATP synthase requiring different numbers of c-subunit rotations for NADH vs FADH2 substrates
Explanation
NADH donates electrons at Complex I (entering at CoQ), where 4 protons are pumped across the inner mitochondrial membrane per 2 electrons (Complex I pumps 4H+). These electrons then pass through Complexes III and IV (each pumping 4H+ and 2H+ respectively). FADH2-linked substrates bypass Complex I and enter at CoQ directly — therefore the 4H+ that Complex I would pump are NOT pumped. With fewer total protons (28H+ for NADH vs 20H+ for FADH2 per 2 electrons, approximately), and F0F1-ATPase requiring ~8 protons per ATP, the P/O ratio for NADH (~2.5) exceeds that for FADH2 (~1.5). NADH has a MORE negative (lower) redox potential than FADH2 — more energy released in that span.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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