[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Electron transport chain and oxidative phosphorylation [Biochemistry](https://durgical.com/en/biochemistry/) · Metabolic pathway # Electron transport chain and oxidative phosphorylation The respiratory chain passes electrons from NADH and FADH₂ to oxygen; the energy pumps protons, and ATP synthase uses them to make most of the cell's ATP. Updated 2026-11-01 ## Interactive map ## Key facts - It runs in the inner mitochondrial membrane: complexes I, III and IV pump protons as they pass electrons towards O₂, the final acceptor. - Two doors to ubiquinone: NADH enters at complex I and FADH₂ at complex II (succinate dehydrogenase), which pumps no protons. - Approximate yield: about 2.5 ATP per NADH and 1.5 ATP per FADH₂; about 30–32 ATP per fully oxidised glucose. - Protons pumped per electron pair from NADH: 4 (complex I) + 4 (complex III) + 2 (complex IV) = 10; each ATP costs about 4 H⁺ including phosphate transport. - Without O₂, or with cyanide or CO, the chain stops: NADH is not reoxidised, the Krebs cycle slows and pyruvate ends up as lactate. ## Memory aid Inhibitors by complex: “Rotenone-I, Antimycin-III, Cyanide and CO-IV, Oligomycin-V”. **Also called** Respiratory chain, Mitochondrial electron transport chain ## Regulation - Respiratory control: electron flow depends on ADP; if the cell does not spend ATP, the high gradient slows the chain. - Uncouplers (UCP1, 2,4-dinitrophenol) let protons return without passing through ATP synthase: the chain speeds up and the energy leaves as heat. - ATP demand and the Ca²⁺ of contracting muscle activate the dehydrogenases that feed NADH to the chain. ## The steps, one by one - **Step 1 · [Complex I (NADH:ubiquinone oxidoreductase)](https://durgical.com/en/biochemistry/enzymes/complex-i/)** irreversible NADH + [Ubiquinone](https://durgical.com/en/biochemistry/molecules/ubiquinone/) → Ubiquinol (QH₂) + [NAD⁺](https://durgical.com/en/biochemistry/molecules/nad/) Takes 2 electrons from NADH, passes them through FMN and a row of Fe-S clusters to ubiquinone, and pumps 4 H⁺ into the intermembrane space. **If it fails:** Variants in the MT-ND genes cause Leber hereditary optic neuropathy; complex I defects are the most common cause of Leigh syndrome. [Leber hereditary optic neuropathy (LHON) →](https://durgical.com/en/conditions/leber-hereditary-optic-neuropathy/) - **Step 2 · [Complex III (cytochrome bc₁)](https://durgical.com/en/biochemistry/enzymes/complex-iii/)** irreversible Ubiquinol (QH₂) + Cytochrome c (Fe³⁺) → Cytochrome c (Fe²⁺) + [Ubiquinone](https://durgical.com/en/biochemistry/molecules/ubiquinone/) Q cycle: each ubiquinol gives one electron to cytochrome c through the Rieske centre and sends the other back to ubiquinone through the b hemes; 4 H⁺ are released per pair. **If it fails:** Variants in MT-CYB and in assembly genes such as BCS1L cause myopathy with exercise intolerance and, sometimes, Leigh syndrome. - **Step 3 · [Complex IV (cytochrome c oxidase)](https://durgical.com/en/biochemistry/enzymes/cytochrome-c-oxidase/)** irreversible Cytochrome c (Fe²⁺) + o2 → H⁺ gradient + H₂O Takes 4 electrons from 4 cytochrome c molecules, reduces one O₂ to 2 H₂O and pumps 2 H⁺ per pair: with complexes I and III it completes the gradient. **If it fails:** Cyanide and CO block it: the cell cannot use O₂ even when it arrives. Variants in SURF1, which assembles the complex, are a classic cause of Leigh syndrome. [Cyanide poisoning →](https://durgical.com/en/conditions/cyanide-poisoning/) - **Step 4 · [ATP synthase (complex V)](https://durgical.com/en/biochemistry/enzymes/atp-synthase/)** H⁺ gradient + ADP + phosphate (Pi) ⇌ ATP in the matrix + H₂O H⁺ flow back into the matrix through the Fo channel and spin it; the rotation changes the shape of the F1 β subunits, which bind ADP and phosphate and release ATP. **If it fails:** MT-ATP6 variants cause NARP (neuropathy, ataxia and retinitis pigmentosa) and maternally inherited Leigh syndrome. [Leigh syndrome →](https://durgical.com/en/conditions/leigh-syndrome/) - **Step 5 · Adenine nucleotide translocase (ANT)** irreversible ATP in the matrix + ADP → ATP in the cytosol Exports newly made ATP to the cytosol in exchange for an incoming ADP; the swap uses part of the membrane potential. Phosphate enters on its own carrier. **If it fails:** SLC25A4 (ANT1) variants cause progressive external ophthalmoplegia and cardiomyopathy with myopathy. ## Clinical notes - Cyanide and carbon monoxide block complex IV: tissue hypoxia with lactic acidosis even though the blood carries oxygen. - Mitochondrial diseases (MELAS, LHON, Leigh syndrome) hit the brain, retina, muscle and heart hardest, the tissues that spend the most ATP. - Complexes I and III are the cell's main source of superoxide; antioxidant defences keep it in check. - Mitochondrial DNA is inherited from the mother, and each cell can carry a mix of normal and mutant copies (heteroplasmy). ## Pathways - [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/) - [Glycolysis](https://durgical.com/en/biochemistry/pathways/glycolysis/) ## Related conditions - [Cyanide poisoning](https://durgical.com/en/conditions/cyanide-poisoning/) - [Carbon monoxide poisoning](https://durgical.com/en/conditions/carbon-monoxide-poisoning/) - [MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes)](https://durgical.com/en/conditions/melas/) - [Leber hereditary optic neuropathy (LHON)](https://durgical.com/en/conditions/leber-hereditary-optic-neuropathy/) - [Leigh syndrome](https://durgical.com/en/conditions/leigh-syndrome/) - [Lactic acidosis](https://durgical.com/en/conditions/lactic-acidosis/) - [Hereditary paraganglioma and pheochromocytoma (SDH)](https://durgical.com/en/conditions/hereditary-paraganglioma-and-pheochromocytoma/) ## Related - [Complex I (NADH dehydrogenase)](https://durgical.com/en/biochemistry/enzymes/complex-i/) - [Complex III (cytochrome bc₁)](https://durgical.com/en/biochemistry/enzymes/complex-iii/) - [Cytochrome c oxidase (complex IV)](https://durgical.com/en/biochemistry/enzymes/cytochrome-c-oxidase/) - [ATP synthase (complex V)](https://durgical.com/en/biochemistry/enzymes/atp-synthase/) - [Succinate dehydrogenase (complex II)](https://durgical.com/en/biochemistry/enzymes/succinate-dehydrogenase/) - [Ubiquinone (coenzyme Q₁₀)](https://durgical.com/en/biochemistry/molecules/ubiquinone/) - [Cytochrome c](https://durgical.com/en/biochemistry/enzymes/cytochrome-c/) - [NAD⁺ (nicotinamide adenine dinucleotide)](https://durgical.com/en/biochemistry/molecules/nad/) - [FAD (flavin adenine dinucleotide)](https://durgical.com/en/biochemistry/molecules/fad/) - [ATP (adenosine triphosphate)](https://durgical.com/en/biochemistry/molecules/atp/) - [UCP1 (thermogenin)](https://durgical.com/en/biochemistry/enzymes/ucp1/) - [Chemiosmosis and the proton gradient](https://durgical.com/en/biochemistry/topics/chemiosmosis-and-the-proton-gradient/) - [Uncouplers of oxidative phosphorylation](https://durgical.com/en/biochemistry/topics/uncouplers-of-oxidative-phosphorylation/) - [Mitochondrial NADH shuttles](https://durgical.com/en/biochemistry/topics/mitochondrial-nadh-shuttles/) - [Reactive oxygen species and antioxidants](https://durgical.com/en/biochemistry/topics/reactive-oxygen-species-and-antioxidants/) - [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/) - [Glycolysis](https://durgical.com/en/biochemistry/pathways/glycolysis/) ## Test yourself Think of the answer, then tap the question to see it. ## About how much ATP do one NADH and one FADH₂ yield in the respiratory chain? About 2.5 per NADH and 1.5 per FADH₂: FADH₂ enters at complex II, which pumps no protons, and skips complex I. ## Which complex of the chain pumps no protons? Complex II (succinate dehydrogenase): it passes FADH₂'s electrons to ubiquinone without moving H⁺. ## What is the final electron acceptor of the respiratory chain? Oxygen: complex IV reduces it to water with 4 electrons and 4 protons. ## Which classic inhibitor acts on each complex? Rotenone on I, antimycin A on III, cyanide, CO and azide on IV, and oligomycin on ATP synthase. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/pathways/electron-transport-chain-and-oxidative-phosphorylation/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Respiratory electron transport](https://reactome.org/PathwayBrowser/#/R-HSA-611105) (Reactome, 2026); [Formation of ATP by chemiosmotic coupling](https://reactome.org/PathwayBrowser/#/R-HSA-163210) (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011). [← All of biochemistry](https://durgical.com/en/biochemistry/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/biochemistry/pathways/electron-transport-chain-and-oxidative-phosphorylation/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/pathways/electron-transport-chain-and-oxidative-phosphorylation/