Electron Transport Chain Notes

Electron Transport Chain

• The electron transport chain (ETC) is the final common pathway that uses harvested electrons from various fuels to generate ATP.
• The proton gradient, not the flow of electrons, is what ultimately produces ATP.
• Aerobic metabolism, which occurs in the mitochondria in eukaryotes, is the most efficient way to generate energy.
• Anaerobic processes like glycolysis and fermentation occur in the cytosol.

Mitochondrial Components

• The citric acid cycle occurs in the mitochondrial matrix.
• Oxidative phosphorylation occurs in the inner mitochondrial membrane.
• The inner mitochondrial membrane is folded into cristae to maximize surface area.
• The inner mitochondrial membrane generates ATP using the proton motive force, an electrochemical proton gradient.

Electron Transport and ATP Generation

• The final step in aerobic respiration involves electron transport and ATP generation (ADP phosphorylation), which are coupled processes.
• NADH and FADH2 transfer electrons to carrier proteins in the inner mitochondrial membrane.
• Electrons are passed to oxygen, forming water.
• Energy released during electron transport facilitates proton transport from the mitochondrial matrix to the intermembrane space creating a proton gradient.

Coupling Electron Transport to ATP production

• ATP formation is endergonic, while electron transport is exergonic.
• Coupling these reactions allows the energy from electron transport to fuel ATP formation.
• Proteins in the inner membrane transfer electrons donated by NADH and FADH2 in a specific order based on reduction potential.
• The molecule with the higher reduction potential is reduced, while the other is oxidized.
• NADH is a good electron donor, and oxygen is the final electron acceptor.

Complexes of the Electron Transport Chain

• Complex I: NADH-CoQ Oxidoreductase
  • Transfers electrons from NADH to coenzyme Q (CoQ).
  • Contains a flavoprotein with flavin mononucleotide (FMN, similar to FAD).
  • Process:
    • NADH transfers electrons to FMN, becoming oxidized to NAD^+, while FMN is reduced to FMNH_2.
    • The flavoprotein is reoxidized as the iron-sulfur subunit is reduced.
    • The reduced iron-sulfur subunit donates electrons to CoQ, forming CoQH_2.
  • Equation:
    • NADH + H^+ + FMN \rightarrow NAD^+ + FMNH_2
    • FMNH2 + 2FeS{ox} \rightarrow FMN + 2FeS_{red} + 2H^+
    • 2FeS{red} + CoQ + 2H^+ \rightarrow 2FeS{ox} + CoQH_2
    • Net: NADH + H^+ + CoQ \rightarrow NAD^+ + CoQH_2
  • Pumps four protons into the intermembrane space.
• Complex II: Succinate-CoQ Oxidoreductase
  • Transfers electrons from succinate to coenzyme Q.
  • FAD is covalently bonded to complex II and is reduced to FADH2 when succinate is oxidized to fumarate. The FADH2 then transfers its electrons to CoQ.
  • Succinate dehydrogenase (citric acid cycle enzyme) is part of complex II.
  • No proton pumping occurs here.
  • Equation:
    • Succinate + FAD \rightarrow Fumarate + FADH_2
    • FADH2 + FeS{ox} \rightarrow FAD + FeS_{red}
    • FeS{red} + CoQ + 2H^+ \rightarrow FeS{ox} + CoQH_2
    • Net: Succinate + CoQ + 2H^+ \rightarrow Fumarate + CoQH_2
• Complex III: CoQH2-Cytochrome c Oxidoreductase (Cytochrome Reductase)
  • Transfers electrons from coenzyme Q to cytochrome c.
  • Involves oxidation and reduction of cytochromes (proteins with heme groups containing iron).
  • Coenzyme Q has two electrons to transfer, so two cytochrome c molecules are needed.
  • Equation:
    • CoQH_2 + 2Cytochrome \ c \ (Fe^{3+}) \rightarrow CoQ + 2Cytochrome \ c \ (Fe^{2+}) + 2H^+
  • Q cycle: transfers two electrons from CoQH_2 near the intermembrane space to CoQ near the mitochondrial matrix, while also reducing two molecules of cytochrome c and displacing four protons to the intermembrane space.
  • Increases the proton gradient.
• Complex IV: Cytochrome c Oxidase
  • Transfers electrons from cytochrome c to oxygen (the final electron acceptor), forming water.
  • Includes subunits of cytochrome a, cytochrome a3, and Cu^{2+} ions; cytochromes a and a3 form cytochrome oxidase.
  • Proton pumping occurs (two protons are moved across the membrane).
  • Equation:
    • 4 \ Cytochrome \ c \ (Fe^{2+}) + 4H^+ + O2 \rightarrow 4 \ Cytochrome \ c \ (Fe^{3+}) + 2H2O

Proton Motive Force

• As H^+ increases in the intermembrane space:
  • pH decreases (becomes more acidic).
  • Voltage difference increases (more positive charge).
• These changes create an electrochemical gradient called the proton motive force.
• ATP synthase harnesses this energy to form ATP from ADP and inorganic phosphate.

NADH Shuttles

• Net ATP yield per glucose ranges from 30 to 32 due to variable efficiency of aerobic respiration in cells.

• Cytosolic NADH from glycolysis cannot directly cross into the mitochondrial matrix; it uses shuttle mechanisms.

• Shuttle mechanisms transfer high-energy electrons of NADH to a carrier that can cross the inner mitochondrial membrane.

• Depending on the shuttle mechanism 1.5 or 2.5 ATP are produced per NADH.

• Glycerol 3-Phosphate Shuttle

  • Cytosolic glycerol 3-phosphate dehydrogenase oxidizes cytosolic NADH to NAD^+, forming glycerol 3-phosphate from dihydroxyacetone phosphate (DHAP).
  • A different isoform of glycerol 3-phosphate dehydrogenase on the outer face of the inner mitochondrial membrane is FAD-dependent and reduces FAD to FADH_2.
  • FADH_2 transfers electrons to the ETC via complex II, generating 1.5 ATP per cytosolic NADH.

• Malate-Aspartate Shuttle

  • Cytosolic oxaloacetate (impermeable to the inner mitochondrial membrane) is reduced to malate (permeable) by cytosolic malate dehydrogenase, oxidizing cytosolic NADH to NAD^+.
  • Malate crosses into the matrix, and mitochondrial malate dehydrogenase reverses the reaction to form mitochondrial NADH.
  • NADH passes electrons to the ETC via complex I, generating 2.5 ATP per molecule of NADH.
  • Malate is recycled by oxidation to oxaloacetate, which is transaminated to form aspartate.
  • Aspartate crosses into the cytosol and is converted back to oxaloacetate to restart the cycle.