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Electron transport chain and oxidative phosphorylation

Last updated: January 22, 2021

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Oxidative phosphorylation is a metabolic pathway through which cells release the energy stored in carbohydrates, fats, and proteins to produce adenosine triphosphate (ATP), the main source of energy for intracellular reactions. The process takes place within the mitochondria and involves oxidation-reduction reactions and the generation of an electrochemical gradient by the electron transport chain. The electron transport chain (mitochondrial respiratory chain) is embedded in the inner mitochondrial membrane and consists of four electron carrier complexes (complexes I–IV) that transfer electrons from nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) to oxygen, thereby generating water (H2O). The electron carrier complexes not only transfer electrons, but also pump protons out of the mitochondrial matrix into the mitochondrial intermembrane space, thereby creating an electrochemical gradient. Re-entry of these protons through ATP-synthase (complex V) into the mitochondrial matrix results in the phosphorylation of adenosine diphosphate (ADP) into ATP. Uncoupling agents, such as aspirin and 2,4-dinitrophenol, dissociate the electron transport chain from ATP synthesis by reducing the electrochemical gradient across the mitochondrial membrane. Oligomycin inhibits ATP synthesis by blocking the reflux of protons through ATP-synthase. In states of prolonged hypoxia (e.g., cardiac ischemia), the electron transport chain will stop running, ATP will no longer be produced, and cells may die.

Overview of ATP synthesis [1]

Sources of ATP synthesis

Sources of ATP synthesis and their caloric value
Source Breakdown Storage form Characteristics Caloric value (kcal/g)
  • 4 kcal/g
  • See “Lipids and fat metabolism”
  • 9 kcal/g
Ketone bodies
  • Usually not stored
  • Constantly produced in small amounts by the liver
  • 4 kcal/g [2]

Pathways of ATP synthesis

  • Storage of ATP is very limited and requires constant reproduction.
  • The mechanism by which ATP is produced depends on the type of activity (i.e., the energy demand) and the oxygen supply.
ATP synthesis
Type of metabolism Type of activity Pathway
Aerobic metabolism
  • Resting and nonstrenuous exercise states (e.g., walking)
Anaerobic metabolism
  • Sustained strenuous exercise
  • Sudden, short bursts of rapid movement
Protein metabolism

Overview of oxidative phosphorylation and the electron transport chain

Oxidative phosphorylation and the electron transport chain
Electron transport chain Oxidative phosphorylation
  • Production of ATP, which provides energy for intracellular reactions
ATP produced

Overview of the phosphagen system [3]

Phosphagen reactions
Adenylate kinase reaction Creatine kinase reaction
Location of enzyme
Transfer of phosphate

ATP and phosphocreatine are both important short-term energy stores in muscle cells.

Protein complexes of electron transport chain and oxidative phosphorylation
Reactions Equation
Electron transport chain
Complex I (NADH dehydrogenase)
  • Transfers two protons (H+) and two electrons (e-) to coenzyme Q
  • Pumps four protons into the intermembrane space
Complex II (contains succinate dehydrogenase )
  • Transfers two protons (H+) and two electrons (e-) to coenzyme Q
  • Does not pump protons into the intermembrane space
Complex III (coenzyme Q-cytochrome c reductase)
  • Transfers two electrons (e-) from coenzyme Q to two molecules cytochrome c
  • Transfers 4 protons (H+) into the intermembrane space
Complex IV (cytochrome c oxidase)
Oxidative phosphorylation
Complex V (ATP synthase)
  • Acts as proton channel, works like a turbine → flow of protons allows generation of ATP
  • For every 4 protons, one ATP is generated
  • ADP + Pi → ATP
  • Yield
    • 1 NADH transport of 10 H+ 2.5 ATP
    • 1 FADH2 transport of 6 H+ 1.5 ATP

To remember complex 1 (rotenone) and 3 (antimycin) inhibitors, think: “one rotten carrot, three antsy (anti) mice.”

  1. Feher JJ. Quantitative Human Physiology. Academic Press ; 2017
  2. Reichard GA Jr, Owen OE, Haff AC, Paul P, Bortz WM. Ketone-body production and oxidation in fasting obese humans.. J Clin Invest. 1974; 53 (2): p.508-15. doi: 10.1172/JCI107584 . | Open in Read by QxMD
  3. Baker JS, McCormick MC, Robergs RA. Interaction among Skeletal Muscle Metabolic Energy Systems during Intense Exercise.. J Nutr Metab. 2010; 2010 : p.905612. doi: 10.1155/2010/905612 . | Open in Read by QxMD
  4. Kaplan. USMLE Step 1 Lecture Notes 2018: Biochemistry and Medical Genetics. Kaplan ; 2017
  5. Chatterjea M, Shinde R. Textbook of Medical Biochemistry. JP Medical Ltd ; 2011