Biochemistry - Lesson 15: Oxidative Phosphorylation and Electron Transport Chain
Oxidative phosphorylation couples electron transport along the mitochondrial inner membrane to ATP synthesis via chemiosmosis. NADH and FADH2 feed electrons into the electron transport chain (ETC), releasing energy that pumps protons from the matrix to the intermembrane space, establishing a proton gradient. ATP synthase then uses the resulting proton-motive force to drive ATP production. This stage of aerobic respiration generates the bulk of ATP in most cells.
Electron Transport Chain Overview
The ETC consists of four major complexes (I–IV) embedded in the inner mitochondrial membrane, plus small mobile carriers (coenzyme Q and cytochrome c). Each complex operates at progressively higher redox potential, transferring electrons to oxygen (which is reduced to water).
As electrons flow through these complexes, protons are translocated from the matrix to the intermembrane space (except at complex II), creating a voltage difference and a pH gradient.
Chemiosmosis and ATP Synthase
ATP synthase harnesses the proton gradient to phosphorylate ADP. Protons re-enter the matrix through the enzyme’s rotor section, driving conformational changes in the catalytic head that combine ADP with Pi. This chemiosmotic mechanism is the heart of oxidative phosphorylation.
High H+]) -->|Proton Flow| B((Rotor Complex)) B --> C((Catalytic Head
ATP Synthesis)) C --> D([Matrix
Low H+])
Typically, each NADH yields ~2.5 ATP, while each FADH2 yields ~1.5 ATP, though actual numbers vary depending on shuttle systems and proton leak. This step is central to fueling most aerobic cells.
Uncouplers and Heat Generation
Some substances disrupt the proton gradient by allowing protons to leak into the matrix without producing ATP, releasing energy as heat. Classic uncouplers (like dinitrophenol) collapse the gradient, while brown adipose tissue uses an uncoupling protein (UCP1) to produce heat—especially crucial for newborn thermoregulation.
Regulation and Control
- Respiratory Control: Rate of O2 consumption is governed by ADP availability (energy demand). Higher ADP accelerates electron flow and ATP formation.
- Inhibitors: Compounds like rotenone (complex I), antimycin A (III), or cyanide (IV) block electron flow, halting ATP synthesis.
- Substrate Supply: NADH, FADH2, and O2 availability set the maximum ATP output. When TCA flux or oxygen is limited, oxidative phosphorylation slows.
ATP Yield and Efficiency
Oxidative phosphorylation supplies the majority of ATP under aerobic conditions, often cited around 30–32 ATP per glucose in eukaryotes (though exact yields differ based on conditions and shuttle usage). The process effectively captures free energy from fuel oxidation, supporting a wide array of cellular functions.
Summary
Oxidative phosphorylation integrates the electron transport chain’s proton pumping with ATP synthase–driven phosphorylation. NADH and FADH2 transfer electrons to complexes I–IV, creating a proton gradient across the mitochondrial inner membrane. ATP synthase taps this gradient to drive ATP formation, sustaining most of the cell’s energy under aerobic conditions. Regulation aligns with energy needs (ADP) and oxygen availability, while uncoupling modulates heat generation. This mechanism underpins efficient ATP production, vital to cellular and organismal homeostasis.
Suggested Reading:
Lehninger Principles of Biochemistry (chapters on electron transport and oxidative phosphorylation)
Biochemistry by Berg, Tymoczko, and Stryer (sections covering ETC complexes, ATP synthase mechanism, regulation)
