Bioenergetics—Source of Free Energy for Proton Pumping in Mitochondria In oxidative phosphorylation, what is the immediate source of free energy (ΔG) that drives protons from the mitochondrial matrix to the intermembrane space against concentration and electrical gradients?

Introduction / Context:
Mitochondrial oxidative phosphorylation harnesses energy from electron transfers to pump protons across the inner membrane, generating a proton motive force. Understanding the energetic coupling clarifies why ATP synthase can later use this gradient to synthesize ATP.

Given Data / Assumptions:

• Electrons flow through Complexes I–IV in the electron transport chain (ETC).
• Protons are pumped at Complexes I, III, and IV.
• ATP synthase does not hydrolyze ATP to pump protons during normal respiration; it uses the gradient to make ATP.

Concept / Approach:
Redox reactions (exergonic) as electrons move from NADH/FADH2 to O2 release free energy. Respiratory complexes couple part of this energy to active proton translocation, building an electrochemical gradient (Δp = ΔΨ + ΔpH). ATP synthase later converts the stored gradient energy into ATP, not vice versa.

Step-by-Step Solution:

Verification / Alternative check:
Inhibitors like rotenone (I), antimycin A (III), or cyanide (IV) block redox steps and abolish proton pumping, demonstrating that the ETC's redox chemistry powers the pumps.

Why Other Options Are Wrong:

• Glycolysis and TCA produce NADH/FADH2 but are not the immediate energy source for pumping.
• Creatine phosphate buffers ATP levels in muscle; not linked to proton pumping.
• ATP is produced by the gradient; it is not consumed to pump H+ in oxidative phosphorylation.

Common Pitfalls:
Assuming ATP hydrolysis drives proton pumping; that occurs in reverse only under special conditions when ATP synthase runs backward.

Final Answer:
The redox reactions of electron transport