U2L4 - Oxidative Phosphorylation

Oxidative Phosphorylation

• Overview of Oxidative Phosphorylation

  • Key players: Electrons, NADH, FADH2

• Mitochondrial Structure

  • Outer mitochondrial membrane: Comprised of phospholipid bilayer.

  • Inner mitochondrial membrane: Site for the electron transport chain.

  • Inner membrane space: Space between inner and outer membranes.

  • Mitochondrial matrix: Area inside the inner membrane.

  • Cristae: Folds of the inner mitochondrial membrane that increase surface area for reactions.

Oxidative Phosphorylation Details

• Electrons: Oxidized NADH and FADH2 lose electrons leading to the synthesis of vast amounts of ATP.

• Key processes involved:

  • Oxidative Decarboxylation

  • Citric Acid Cycle (CAC)

  • Focus on coenzyme complexes within the Electron Transport Chain (ETC).

The Electron Transport Chain

• Electron Flow

  • NADH loses two electrons (and two hydrogens), producing NAD+ which is recyclable in glycolysis, oxidative decarboxylation (OD), and citric acid cycle (CAC).

  • The two electrons move into Flavin Mononucleotide (FMN), which becomes reduced. FMN swiftly transfers the electrons to Coenzyme Q, leading to FMN being oxidized and Coenzyme Q being reduced.

• Continuing Electron Transfer:

  • Coenzyme Q passes electrons to Cytochrome b/c1, where Coenzyme Q is oxidized and Cytochrome b/c1 is reduced.

  • Cytochrome b/c1 then transfers electrons to Cytochrome c, oxidizing Cytochrome b/c1 while reducing Cytochrome c.

  • Cytochrome c moves along the phospholipid bilayer to combine with Cytochrome a/a3, transferring electrons and completing a similar oxidation-reduction process.

• Redox Reactions: The process is characterized by a series of alternating oxidations and reductions, culminating with oxygen as the final electron acceptor—reacting with electrons and protons to form water, as follows:

  • Final reaction: O2 + 4e^- + 4H^+ → 2H2O

Hydrogen Ion Dynamics in ATP Production

• Total hydrogens accounted: 20 hydrogens are derived from NADH and FADH2 during the oxidation process linked with the Citric Acid Cycle (CAC).

  • Reaction illustrated:

  • $2C<em>6H</em>{12}O<em>6 + 6O</em>2 + 6H<em>2O ightarrow 6CO</em>2 + 12H_2O$

ATP Production Mechanism

• Peter Mitchell's Discovery (1961)

  • The intermembrane space exhibits a low pH, making it acidic compared to the mitochondrial matrix.

• In terms of hydrogen ions (H^+):

  • The accumulation of H^+ in the intermembrane space leads to a high electric potential gradient across the inner mitochondrial membrane, necessitating energy input (active transport).

• Use of Energy from NADH and FADH2:

  • As NADH donates electrons to FMN, FMN becomes energized and facilitates the active pumping of H+ ions against the concentration gradient into the intermembrane space.

  • Similarly, Cytochrome b/c1 and Cytochrome a/a3 also contribute to pumping H+ ions into the intermembrane space.

• Hydrogen Ion Pumping Summary:

  • Each oxidation of NADH results in 3 pairs of H^+ ions being pumped into the intermembrane space, leading to a net of 30 H^+ ions from 10 NADH.

  • For FADH2, each results in 2 pairs, totaling 4 pairs of H^+ ions from 2 FADH2.

  • In total, from both NADH and FADH2, there are 34 pairs of H^+ ions pumped into the intermembrane space.

ATP Synthase and Energy Conversion

• The ATP synthase enzyme plays a crucial role in ATP production:

  • H^+ ions flow through ATP synthase from high concentration (intermembrane space) to low concentration (matrix).

  • During this process, potential energy is released, which is harnessed for the phosphorylation of ADP to form ATP.

• Total ATP Calculation:

  • With 34 pairs of H^+ ions, up to 34 molecules of ATP can be synthesized through this process.

Chemiosmotic Theory

• Theoretical Framework (Peter Mitchell, 1961):

  • ATP synthesis is indirectly linked to the oxidation of NADH and FADH2.

  • Energy generated from the electron transport chain is exploited to pump H^+ ions into the intermembrane space, creating a concentration gradient that stores potential energy.

  • As H^+ ions return to the mitochondrial matrix via ATP synthase, this energy is utilized to phosphorylate ADP, achieving a maximum production of 34 ATP.