Bioenergetics

Free Energy and Coupling

Metabolic direction follows Gibbs free energy: $\Delta G = \Delta H - T\Delta S$ ATP hydrolysis ($\Delta G^\circ{}' \approx -30.5\ \text{kJ/mol}$) is coupled to unfavorable reactions to pull them forward; summed $\Delta G$ values decide whether a coupled process runs. Electron carriers NAD$^+$ and FAD collect reducing power from catabolism.

The TCA Cycle

In the mitochondrial matrix, acetyl-CoA condenses with oxaloacetate to citrate, and each turn regenerates oxaloacetate while capturing energy: $3\,\text{NADH} + 1\,\text{FADH}_2 + 1\,\text{GTP per acetyl-CoA}$ The cycle itself uses no oxygen but stops without it, because the electron transport chain must recycle NAD$^+$ and FAD. Isocitrate dehydrogenase is the key regulated step.

Electron Transport and Chemiosmosis

Complexes I, III, and IV pump protons as electrons flow from NADH (Complex II accepts FADH$_2$ without pumping) to the final acceptor O$_2$. The proton-motive force drives ATP synthase — chemiosmosis — yielding roughly 2.5 ATP per NADH, 1.5 per FADH$_2$, about 30-32 ATP per glucose. Cyanide blocks Complex IV and halts everything; uncouplers dissipate the gradient as heat.

Key Takeaways

• Coupling to ATP hydrolysis makes endergonic steps run.
• Per glucose, the TCA cycle contributes 6 NADH, 2 FADH$_2$, 2 GTP.
• FADH$_2$ yields less ATP because Complex II pumps no protons.
• Blocking the chain and uncoupling it fail differently: no gradient versus wasted gradient.