Question
Explain the electron transport chain (Complexes I-IV) and ATP synthase. How does oxidative phosphorylation produce ATP?
Solution — Step by Step
flowchart LR
A[NADH] --> B[Complex I - NADH dehydrogenase]
B -->|e- via UQ| C[Complex III - Cyt bc1]
C -->|e- via Cyt c| D[Complex IV - Cyt c oxidase]
D --> E[O2 + H+ = H2O]
F[FADH2] --> G[Complex II - Succinate dehydrogenase]
G -->|e- via UQ| C
B -->|H+ pumped| H[Intermembrane Space]
C -->|H+ pumped| H
D -->|H+ pumped| H
H -->|H+ gradient| I[ATP Synthase - Complex V]
I --> J[ATP]
NADH donates 2 electrons to Complex I on the inner mitochondrial membrane. The electrons pass through FMN and iron-sulphur clusters. As electrons move through, 4 H ions are pumped from the matrix to the intermembrane space. Electrons are passed to ubiquinone (CoQ).
FADH (from the Krebs cycle) donates electrons to Complex II. This complex does NOT pump H ions — which is why FADH produces fewer ATP than NADH. Electrons are also passed to ubiquinone.
Ubiquinone carries electrons to Complex III. Electrons pass through cytochrome b and cytochrome c. 4 H ions are pumped across. Electrons are transferred to the mobile carrier cytochrome c.
Cytochrome c delivers electrons to Complex IV. Here, electrons are finally transferred to molecular oxygen (O) — the terminal electron acceptor. O combines with electrons and H to form HO. 2 H are pumped. This is why we breathe — to provide the O that accepts electrons at the end of the chain.
The H gradient (high concentration in intermembrane space, low in matrix) drives H back through ATP synthase (a molecular turbine). The flow of H through the F channel rotates the F head, which catalyses: . This is chemiosmotic coupling (Peter Mitchell’s chemiosmotic hypothesis). Each NADH produces about 2.5 ATP; each FADH produces about 1.5 ATP.
Why This Works
Oxidative phosphorylation couples electron transport (an exergonic process) with ATP synthesis (an endergonic process) through a proton gradient. The energy released as electrons flow “downhill” through the chain is used to pump H, creating potential energy. This energy is then harnessed by ATP synthase. About 34 of the 36-38 ATP from glucose oxidation come from oxidative phosphorylation.
Common Mistake
Students assume NADH and FADH produce the same amount of ATP. They do NOT. NADH enters at Complex I (3 proton-pumping sites), yielding ~2.5 ATP. FADH enters at Complex II (bypasses Complex I, only 2 pumping sites), yielding ~1.5 ATP. This 1 ATP difference per molecule adds up significantly.
Remember the terminal electron acceptor is O. If O is absent, the ETC stops completely — electrons cannot flow, NADH and FADH cannot be reoxidised, and the Krebs cycle also halts. This is why cyanide (which blocks Complex IV) is lethal — it stops the entire respiratory chain.