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Oxidative Phosphorylation P1

1. ATP: The Cell's Energy Currency

  • ATP → ADP + Pi releases -7.3 kcal/mol

  • Used as the immediate source of energy (not long-term storage).

  • Adult body contains ~100g ATP but recycles its entire body weight in ATP daily.

  • Hence, constant regeneration of ATP is essential.

2. Where the Energy Comes From

  • ATP is generated by coupling the transfer of high-energy electrons (from food) to phosphorylation of ADP.

  • One molecule of glucose produces ~30 ATP:

    • 26 via oxidative phosphorylation

    • 2 from glycolysis

    • 2 from the TCA cycle

3. The Role of Oxygen

  • Oxygen is the terminal electron acceptor in the chain.

  • The challenge: safely and gradually transfer electrons to O₂ (a reactive species) without causing cellular damage.

4. The Electron Transport Chain (ETC)

  • Located on the inner mitochondrial membrane.

  • Electrons pass through a series of carriers with increasing redox potential.

  • Energy is released stepwise → used to pump protons into the intermembrane space.

5. Redox Potential and Free Energy

  • Electrons flow from low to high redox potential:

    • e.g., NADH (E°′ = –0.32 V) → O₂ (E°′ = +0.82 V)

    • ΔE = +1.14 V → ΔG = –220 kJ/mol

  • This energy is used to establish a proton gradient (not directly to make ATP).

6. Chemiosmotic Theory

  • Proposed by Peter Mitchell.

  • The proton motive force (PMF) generated by proton pumping drives ATP synthesis.

  • ATP synthase uses this PMF to convert ADP + Pi → ATP.

7. Structure of the Mitochondrion

  • Double membrane: outer (permeable), inner (impermeable, with cristae).

  • Cristae increase surface area for ETC.

  • Compartments:

    • Matrix: enzymes of TCA, fatty acid oxidation

    • Intermembrane space: site of proton accumulation

8. Electron Transport Chain Complexes

  • Complex I (NADH:Q oxidoreductase)

    • NADH → FMN → Fe-S clusters → Q → QH₂

    • Pumps 4 H⁺

  • Complex II (Succinate-Q reductase)

    • Succinate → FADH₂ → Fe-S clusters → Q → QH₂

    • No proton pumping

  • Q Pool

    • Mobile pool of ubiquinone (Q) / ubiquinol (QH₂)

  • Complex III (Q-cytochrome c oxidoreductase)

    • QH₂ donates e⁻ via Q cycle to cytochrome c

    • Pumps 4 H⁺

  • Cytochrome c

    • Carries electrons between Complex III → Complex IV

    • Contains heme group; mobile and conserved

  • Complex IV (Cytochrome c oxidase)

    • Accepts electrons → O₂ → H₂O

    • Uses heme a, a₃ and copper centers (CuA, CuB)

    • Pumps 2 H⁺ per 2 e⁻

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9. Cofactors in the ETC

  • FMN: accepts 2 e⁻ from NADH

  • Fe-S clusters: 1 e⁻ at a time

  • Hemes (a, b, c): single e⁻ transfers

  • Copper centers: involved in O₂ reduction in Complex IV

  • Ubiquinone (CoQ): lipid-soluble, shuttles 1 or 2 e⁻

10. Mitochondrial Membrane Lipids

  • Cardiolipin: unique to inner mitochondrial membrane; stabilizes ETC complexes

  • PE and PC: structural support and membrane curvature

11. Endosymbiotic Origin of Mitochondria

  • All mitochondria evolved from an engulfed bacterial ancestor (e.g., R. prowazekii).

  • Retain bacterial-type genome and ribosomes.

✅ Summary of Key Steps (Biological Order)

  1. Food → NADH/FADH₂ (TCA Cycle)

  2. NADH/FADH₂ → ETC Complexes (I–IV)

  3. Electron flow → proton gradient

  4. Proton flow through ATP synthase → ATP

  5. O₂ accepts electrons → H₂O formation