The P/O ratio for NADH oxidation via the mitochondrial ETC is approximately 2.5 ATP per NADH. This is lower than the theoretical maximum because:

• A The ATP synthase has 50% efficiency
• B FADH2 is used instead of NADH at complex II
• C Proton pumping is unidirectional and some energy is lost as sound
• D Some protons leak across the inner mitochondrial membrane without passing through ATP synthase ✓

Explanation

The theoretical P/O ratio is reduced for several reasons: (1) natural proton leak across the inner mitochondrial membrane (through uncoupling proteins like UCP1 in brown adipose tissue and non-specific membrane permeability) dissipates the proton gradient as heat without ATP synthesis; (2) the H+/ATP stoichiometry of ATP synthase (approximately 8-10 protons per 3 ATP synthesized, i.e., ~2.7 H+/ATP); (3) the cost of transporting ATP out of the mitochondria (adenine nucleotide translocase exchanges ADP for ATP across inner membrane). The actual P/O is 2.5 for NADH and 1.5 for FADH2 (enters at complex II, below complex I, pumping fewer protons).

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

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