Electron Transport Chain
On this page
Direct answer
The electron transport chain (respiratory chain) is the set of four enzyme complexes (I–IV) plus ATP synthase (Complex V) on the inner mitochondrial membrane that transfers electrons from NADH and FADH2 to oxygen, pumping protons into the intermembrane space. The proton gradient so created drives ATP synthase — chemiosmotic oxidative phosphorylation. By the modern convention one NADH yields about 2.5 ATP and one FADH2 about 1.5 ATP.
What you must remember
- Complex I (NADH dehydrogenase, contains FMN and iron-sulphur proteins) and Complex III (cytochrome bc1) each pump four protons; Complex IV (cytochrome c oxidase, cytochromes a and a3 with copper) pumps two and transfers electrons to oxygen, forming water.
- Complex II is succinate dehydrogenase; it accepts electrons from FADH2 and feeds them to ubiquinone without pumping protons — the reason FADH2 yields less ATP than NADH.
- Ubiquinone (coenzyme Q) and cytochrome c are the mobile carriers that shuttle electrons between the complexes.
- Inhibitors: rotenone and amobarbital block Complex I; antimycin A blocks Complex III; cyanide, carbon monoxide, hydrogen sulphide and azide block Complex IV; oligomycin blocks the Fo portion of ATP synthase; atractyloside blocks the adenine nucleotide translocase.
- Uncouplers — 2,4-dinitrophenol and the physiological thermogenin (UCP-1) of brown adipose tissue — carry protons back across the membrane, so electron transport and heat production rise while ATP synthesis falls.
- Yields: NADH about 2.5 ATP and FADH2 about 1.5 ATP (older texts say three and two); complete oxidation of one glucose yields roughly 30–32 ATP.
- Cytosolic NADH enters through shuttles — the malate-aspartate shuttle preserves NADH (2.5 ATP), while the glycerol-3-phosphate shuttle converts it to FADH2 (1.5 ATP).
Common confusion
The classic error is mixing up inhibitors with uncouplers. Oligomycin stops ATP synthesis and, secondarily, electron transport, because the gradient cannot be discharged; 2,4-dinitrophenol stops ATP synthesis while electron transport speeds up, since protons leak back without passing through ATP synthase. If a question says oxygen consumption increases but ATP falls, the answer is an uncoupler, not an inhibitor.
Exam-focused takeaway
In theory answers, draw the chain with complexes, proton-pumping sites, mobile carriers, the inhibitors and the P/O ratio, and explain the chemiosmotic mechanism of Peter Mitchell. Viva questions centre on cyanide poisoning (histotoxic hypoxia from cytochrome oxidase blockade) and why FADH2 yields fewer ATP than NADH. MCQs love inhibitor–site matching, thermogenin in brown fat of neonates, oligomycin versus dinitrophenol, and the two shuttles with their different ATP yields.
Frequently asked questions
Why does FADH2 yield less ATP than NADH?
FADH2 enters at Complex II through ubiquinone, bypassing Complex I, so fewer protons are pumped across the inner membrane.
How does cyanide poisoning kill?
Cyanide binds cytochrome c oxidase (cytochrome aa3) and stops electron transfer to oxygen; tissues cannot use oxygen despite adequate delivery, causing histotoxic hypoxia.
What is the P/O ratio?
The number of ATP molecules formed per atom of oxygen reduced — about 2.5 for NADH-linked substrates and 1.5 for FADH2-linked substrates.
What are uncouplers, with examples?
Agents that short-circuit the proton gradient so oxidation proceeds without phosphorylation — 2,4-dinitrophenol, and thermogenin, which generates heat in brown adipose tissue of neonates.
Which shuttle carries cytosolic NADH more efficiently?
The malate-aspartate shuttle, yielding 2.5 ATP per NADH, compared with 1.5 ATP through the glycerol-3-phosphate shuttle.