11. Mitochondrial Oxidation. Structure of Electron Transfer Chain (Respiratory Chain). The Coupling of processes of Oxidation and Phosphorylation. Regulation of Electron Transfer Chain: Inhibitors, Uncoupling agents. Thermogenesis.

Mitochondrial Oxidation

1. Overview

• Mitochondrial oxidation refers to the process by which reduced coenzymes (NADH and FADH₂), produced during metabolism, are oxidized to generate energy in the form of ATP.
• This occurs through the Electron Transport Chain (ETC) and Oxidative Phosphorylation, located in the inner mitochondrial membrane.
• It is the final stage of cellular respiration, where the energy from food oxidation is converted into a usable chemical form.

2. Structure of the Electron Transport Chain (Respiratory Chain)

a. Location

• Found in the inner mitochondrial membrane, arranged in four large enzyme complexes (I–IV) plus ATP synthase (Complex V).
• The inner membrane is impermeable to ions, ensuring a proton gradient can be established.

b. Components

• Complex I – NADH: Ubiquinone Oxidoreductase (NADH dehydrogenase)
• Accepts electrons from NADH, transferring them to coenzyme Q (ubiquinone).
• Pumps 4 protons (H⁺) into the intermembrane space.
• Complex II – Succinate Dehydrogenase
• Part of the TCA cycle.
• Transfers electrons from succinate (via FADH₂) to coenzyme Q, but does not pump protons.
• Coenzyme Q (Ubiquinone)
• A mobile electron carrier that transports electrons from Complex I and II to Complex III.
• Complex III – Cytochrome bc₁ Complex
• Transfers electrons from ubiquinol (reduced coenzyme Q) to cytochrome c.
• Pumps 4 protons (H⁺) across the membrane.
• Cytochrome c
• A small soluble protein that carries electrons one at a time from Complex III to Complex IV.
• Complex IV – Cytochrome c Oxidase
• Receives electrons from cytochrome c and passes them to molecular oxygen (O₂), the final electron acceptor.
• O₂ is reduced to water (H₂O).
• Pumps 2 protons (H⁺) across the membrane.
• Complex V – ATP Synthase (F₀F₁ complex)
• Uses the proton motive force generated by the ETC to synthesize ATP from ADP and inorganic phosphate (Pi).

3. The Coupling of Oxidation and Phosphorylation (Oxidative Phosphorylation)

a. Chemiosmotic Theory

• Proposed by Peter Mitchell.
• Describes how electron transport (oxidation) and ATP synthesis (phosphorylation) are coupled through a proton gradient.
• As electrons move through the ETC, protons are pumped from the matrix into the intermembrane space, creating an electrochemical gradient (proton motive force).
• ATP synthase then allows protons to flow back into the matrix, using the released energy to form ATP.

b. ATP Yield

• NADH oxidation yields approximately 3 ATP molecules.
• FADH₂ oxidation yields approximately 2 ATP molecules.

4. Regulation of the Electron Transport Chain

• By Energy Demand (Respiratory Control):
• ETC activity depends on the availability of ADP and Pi.