21a-Biochemistry-Lecture21a | Week 11 - Lecture 2

Oxidative Phosphorylation and Electron Transport Chain

Introduction to Oxidative Phosphorylation

  • Final Stages of Cellular Respiration: Produces ATP through the metabolism of carbohydrates, lipids, and amino acids, resulting in the synthesis and utilization of ATP in cells.

  • Key Players: NAD+ and FAD act as oxidized cofactors that accept electrons from substrates, converting to NADH and FADH2, which then donate electrons to the electron transport chain (ETC) leading to ATP formation.

Energy Flow in Cellular Respiration

  • Three Main Stages:

    1. Acetyl-CoA Production: Oxidation of fatty acids, glucose, and some amino acids.

    2. Citric Acid Cycle: Acetyl groups oxidized; electrons captured in NADH and FADH2.

    3. ETC & Oxidative Phosphorylation: Electrons from NADH and FADH2 are transferred through a series of proteins, culminating in ATP synthesis.

Electron Transport and Proton Translocation

  • Process:

    • Transfer of Electrons: Electrons flow through membrane-bound carriers, driving proton transport from the mitochondrial matrix to the intermembrane space, creating an electrochemical gradient.

    • Proton Gradients: The driving force for ATP synthesis through ATP synthase when protons flow back into the mitochondrial matrix down their concentration gradient (chemiosmosis).

Chemiosmotic Theory

  • Key Concept: An electrochemical gradient of protons across the inner mitochondrial membrane is created through electron transport.

  • Mechanism: The downhill flow of electrons through carriers like NADH and FADH2 couples to the uphill transport of protons against the gradient, enabling ATP formation (ADP + Pi → ATP).

Structure and Function of Mitochondrion

  • Four Compartments:

    1. Outer Membrane: Porous; allows molecules up to 5000 Da to pass.

    2. Intermembrane Space (IMS): Higher proton concentration.

    3. Inner Membrane: Impermeable; contains the ETC; cristae increase surface area for ATP production.

    4. Matrix: Where the citric acid cycle and some metabolism occur, with a lower proton concentration.

Components of the Electron Transport Chain

  • Major Protein Complexes:

    • Complex I (NADH:Ubiquinone Oxidoreductase): Transfers electrons from NADH to ubiquinone (Q); pumps protons into IMS.

    • Complex II (Succinate Dehydrogenase): Transfers electrons from succinate to Q; does not pump protons.

    • Complex III (Ubiquinone:Cytochrome c Oxidoreductase): Transfers electrons from QH2 to cytochrome c; pumps protons into the IMS.

    • Complex IV (Cytochrome Oxidase): Completes the electron transport chain by transferring electrons to oxygen, reducing it to water and pumping protons.

Proton Pumping and Electrochemical Potential

  • Electron Transport and Protone Transport: Each pair of electrons from NADH transports 10 protons, while FADH2 results in 6 protons being translocated across the inner membrane into the IMS, affecting the ATP yield.

  • Free Energy Changes: The transfer of electrons through the ETC is exergonic, driving the protons against their gradient, facilitating ATP synthesis.

Role of Reactive Oxygen Species (ROS)

  • Superoxide Production: A mismatch in electron entry and transfer rates can lead to superoxide formation, causing cellular damage. Protective mechanisms involve enzymes like glutathione utilizing NADPH to counteract ROS effects.

Summary of Key Points

  • Fundamental for ATP Production: The flow of electrons through the ETC ultimately drives ATP synthesis via the establishment of a proton gradient, facilitated by the chemiosmotic mechanism.

  • Health Implications: Understanding these processes is crucial for insights into metabolic disorders and conditions related to oxidative stress.