ATP SYNTHASE

Page 1: Oxidative Phosphorylation via ATP Synthase

• Topic of discussion: The process of oxidative phosphorylation and the role of ATP synthase.

• Context: Information presented during Week 3 on a Wednesday.

Page 2: Key Concept

• Electron Transport Equation: The process of electron transport through the electron transport chain is exergonic (energy-releasing).

• Use of Reduction Potentials: Standard reduction potentials are employed to calculate the free energy change (AG°) in redox reactions during electron transport.

Page 3: Mitochondrial Electron-Transport Chain

• Components of the Chain:

  • Complex I: NADH dehydrogenase (FMN) oxidizes NADH and passes electrons to CoQ.

  • Complex II: FADH2 oxidizes to FAD, injecting electrons into the chain.

  • Complex III: Transfers electrons from CoQ to cytochrome c.

  • Complex IV: Reduces O2 to water using electrons from cytochrome c.

• Location: Electron transport occurs across the inner mitochondrial membrane (IMM), moving protons (H+) into the intermembrane space, creating a proton gradient.

Page 4: Standard Reduction Potentials of Respiratory Chain

• Progressive Reduction Potential: Listed values indicate the standard reduction potential (E°) for various redox couples in the system—including NADH and CoQ.

  • NADH to NAD+: E° = -0.315 V

  • CoQ to ubiquinol: E° = 0.045 V

  • Cytochromes typically have an E° in the positive range, indicating stronger electron acceptance as you progress.

• Final Reduction: Molecular oxygen (O2) as the terminal electron acceptor forms H2O, converting chemical energy into a usable form.

Page 5: Calculation of Free Energy Changes

• Free Energy Changes (AG): Each complex has a specific ΔG°' calculated from E° values:

  • Complex I:

    • Reaction: NADH + CoQ → NAD+ + CoQ (reduced)

    • ΔG°' = -69.5 kJ/mol

  • Complex III:

    • Reaction: CoQ (reduced) + cytochrome c → CoQ + cytochrome c (reduced)

    • ΔG°' = -36.7 kJ/mol

  • Complex IV:

    • Reaction: 2 cytochrome c (reduced) + O2 → 2 cytochrome c (oxidized) + H2O

    • ΔG°' = -112 kJ/mol

• Note: Complex II produces insufficient free energy for ATP synthesis but facilitates electron transport.

Page 6: Key Concepts of ATP Synthase

• Structure: ATP synthase consists of two primary components:

  • F1 Component: Catalyzes the synthesis of ATP.

  • F0 Component: Contains the c-ring whose rotation is powered by the proton gradient, facilitating conformational changes in the F1 component.

• P/O Ratio: Can be calculated, indicating ATP yield per oxygen atom utilized.

• Uncouplers: Molecules that disrupt the proton gradient and uncouple electron transport from ATP synthesis.

Page 7: Coupling Electron Transport and ATP Synthesis

• Mechanism: Protons cannot freely move across the IMM, maintaining a gradient critical for ATP production.

• pH Effect: At low pH (high proton concentration), electron transport occurs more effectively.

• Final Reactions in Matrix: Protons flow back through ATP synthase to generate ATP from ADP and Pi, with water being produced as a byproduct.

Page 8: Subunits of ATP Synthase

• F1FO-ATPase Structure:

  • Anticipated subunits include:

    • 3 α and 3 β subunits in the F1 region.

    • A central stalk (γ) connects the c-ring with stator (b) subunits.

    • Assembly into a functional ATP synthase is critically dependent on these components.

Page 9: Visual Representation of ATP Synthase

• Diagrams highlight the spatial arrangement of subunits and the flow of protons through the ATP synthase machinery, emphasizing structural relationships.

Page 10: Central Stalk Mechanism

• Structure Dynamics: The central stalk of ATP synthase is coiled, facilitating rotational motions crucial for ATP synthesis.

Page 11: Binding Change Mechanism for ATP Synthase

• Mechanisms of Action: Rotation allows transitions between different states of active sites leading to ATP synthesis. Each full rotation corresponds to ATP production.

Page 12: Energy Transformation

• Conversion of Energy Forms:

  • Electrochemical gradient derived from nutrient fuels corresponds to free energy used by ATP synthase to produce mechanical energy (rotation), resulting in the chemical energy form of ATP.

Page 13: Visual Summary of F1FO-ATPase

• Structural Diagrams: Continuation of visual representation detailing flow and synthesis of ATP via ATP synthase.

Page 14: c Subunits of F1FO-ATPase

• Arrangement and Function: Illustrations show how c subunits interact with protons and facilitate rotation, which is essential for ATP generation.

Page 15: URL Reference

• Link provided for additional information relating to biochemistry and mechanisms discussed.

Page 16: Mechanism of c Subunit Proton Grabbing

• Proton Grabbing Process: A negatively charged residue grabs a proton, transforming into a less polar variant, indicating the mechanistic action leading to the rotation of c subunits.

• Efficiency: Human ATP synthesis yields 3 ATP molecules per full rotation of the c subunits, correlating to the movement of 10 protons.