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.