Electron Transport Chain Components

Why This Matters

The electron transport chain (ETC) isn't just a series of proteins to memorize—it's the molecular machinery that explains how cells convert food into usable energy. You're being tested on your understanding of redox chemistry, proton gradients, and chemiosmotic coupling, all working together in a precise sequence. Every complex has a specific role: accepting electrons, passing them along, and (in most cases) pumping protons to build the gradient that ultimately drives ATP synthesis.

When you encounter ETC questions, examiners want to see that you understand the flow of electrons from high to low energy, why some entry points yield more ATP than others, and how the proton-motive force connects electron transfer to phosphorylation. Don't just memorize which complex does what—know why electron carriers are arranged in order of increasing reduction potential, and how disrupting any component affects the entire system.

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Electron Entry Points

The ETC has two main entry points for electrons, and understanding the difference is crucial for calculating ATP yield and predicting the effects of metabolic inhibitors.

NADH

• Primary electron donor from glycolysis, pyruvate oxidation, and the citric acid cycle—delivers electrons at the highest energy level in the chain
• Feeds electrons to Complex I, initiating proton pumping at the first of three pumping sites
• Yields ~2.5 ATP per molecule because electrons enter early and pass through all three proton-pumping complexes

$FADH_2$

• Secondary electron donor produced primarily during succinate oxidation in the citric acid cycle
• Enters at Complex II, bypassing Complex I entirely and missing one proton-pumping site
• Yields ~1.5 ATP per molecule—this lower yield explains why $FADH_2$-producing reactions contribute less to total ATP output

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Proton-Pumping Complexes

These three complexes do the heavy lifting of building the proton gradient. Each one couples electron transfer to proton translocation across the inner mitochondrial membrane.

Complex I (NADH Dehydrogenase)

• Largest ETC complex—oxidizes NADH and transfers electrons to ubiquinone while pumping 4 $H^+$ per NADH
• Contains FMN and iron-sulfur clusters that facilitate the multi-step electron transfer through the complex
• First coupling site in the chain; inhibitors like rotenone block here, halting NADH-dependent respiration entirely

Complex III (Cytochrome $bc_1$ Complex)

• Transfers electrons from ubiquinol to cytochrome c while pumping 4 $H^+$ via the Q-cycle mechanism
• Contains heme groups and iron-sulfur clusters—the Rieske iron-sulfur protein is essential for electron bifurcation
• Q-cycle doubles proton pumping efficiency by oxidizing two ubiquinol molecules per pair of electrons delivered to cytochrome c

Complex IV (Cytochrome c Oxidase)

• Terminal oxidase—transfers electrons to $O_2$, the final electron acceptor, forming $H_2O$
• Pumps 2 $H^+$ while consuming 4 additional protons to reduce oxygen: $4e^- + 4H^+ + O_2 \rightarrow 2H_2O$
• Contains copper centers ($Cu_A$, $Cu_B$) and heme groups that coordinate the four-electron reduction of oxygen without releasing reactive intermediates

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Non-Pumping Complex

Not every ETC component contributes to the proton gradient directly—understanding this exception is essential for ATP yield calculations.

Complex II (Succinate Dehydrogenase)

• Dual function enzyme—catalyzes succinate → fumarate in the citric acid cycle and feeds electrons into the ETC
• Does NOT pump protons, which is why $FADH_2$ yields less ATP than NADH
• Contains FAD covalently bound to the enzyme, plus iron-sulfur clusters and heme b that prevent electron leak to oxygen

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Mobile Electron Carriers

These small molecules shuttle electrons between the large complexes, providing flexibility and allowing multiple complexes to feed into common carriers.

Coenzyme Q (Ubiquinone)

• Lipid-soluble carrier embedded in the inner mitochondrial membrane—collects electrons from Complexes I and II
• Exists in three redox states: ubiquinone (oxidized), semiquinone (radical), and ubiquinol (fully reduced, $QH_2$)
• Pool behavior allows it to integrate electrons from multiple sources, including glycerol-3-phosphate dehydrogenase and electron-transferring flavoprotein

Cytochrome c

• Water-soluble heme protein located in the intermembrane space—shuttles electrons from Complex III to Complex IV
• Single-electron carrier due to its single heme group, requiring two cytochrome c molecules per electron pair
• Moonlights in apoptosis—release into the cytosol triggers caspase activation, linking mitochondrial damage to programmed cell death

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Energy Coupling Components

The proton gradient is useless without a mechanism to harness it—these components complete the chemiosmotic circuit.

Proton Gradient (Proton-Motive Force)

• Electrochemical gradient across the inner mitochondrial membrane—combines $\Delta pH$ (~0.5-1.0 units) and $\Delta \psi$ (~140-180 mV)
• Stores ~20 kJ/mol per proton—this potential energy drives ATP synthesis when protons flow back through ATP synthase
• Created by Complexes I, III, and IV—approximately 10 $H^+$ pumped per NADH oxidized, establishing the gradient that powers phosphorylation

ATP Synthase (Complex V)

• Molecular turbine that couples proton flow to ATP synthesis via a rotary catalytic mechanism
• $F_O$ subunit spans the membrane and forms the proton channel; $F_1$ subunit projects into the matrix and contains catalytic sites
• ~3-4 $H^+$ required per ATP synthesized—the c-ring rotation drives conformational changes in the $\beta$ subunits through binding change mechanism

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Quick Reference Table

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Self-Check Questions

1. Why does $FADH_2$ oxidation yield fewer ATP molecules than NADH oxidation, even though both donate two electrons to the ETC?

2. Which two complexes both transfer electrons to ubiquinone, and what key difference between them affects ATP yield?

3. Compare the roles of Coenzyme Q and cytochrome c: how do their physical properties (solubility, electron capacity) relate to their locations and functions in the ETC?

4. If cyanide inhibits Complex IV, what happens to the proton gradient and why does electron flow through the entire chain stop?

5. Explain how ATP synthase couples proton flow to ATP synthesis—what would happen if the $F_O$ and $F_1$ subunits were physically disconnected?