The Electron Transport Chain

Electrons from NADH and FADH2 pass through a series of protein complexes, losing energy at each step. At complex I, NADH donates electrons that reduce ubiquinone to QH2. These electrons continue through electron transport chain complex III and IV, where oxygen finally accepts them and combines with protons to produce water.

As electrons move through complexes I, III, and IV, energy released pumps protons into the intermembrane space, creating a concentration gradient. Protons flow back through ATP synthase down this gradient, activating the enzyme to convert ADP and inorganic phosphate into ATP, producing approximately 32 ATP molecules per glucose molecule.

Ubiquinone, or Q, acts as a mobile electron carrier between complexes. At complex I, NADH reduces Q to QH2. At complex II, FADH2 also transfers electrons to Q. The QH2 then diffuses to complex III, where it participates in the Q cycle to transfer electrons to cytochrome c.

Inhibitors like rotenone block electron transfer and cause reactive oxygen species accumulation, damaging mitochondrial DNA and cellular components. Carbon monoxide inhibits complex IV by competing for oxygen-binding sites, causing electron accumulation and superoxide radical generation. These effects disrupt ATP production and can lead to cell death.

Rotenone, a pesticide, blocks the Q-binding site at complex I, preventing electron transfer from the Fe-S cluster to ubiquinone. This inhibition halts the electron transport chain and increases reactive oxygen species production, which damages mitochondrial components and can ultimately cause cell death.

The Q cycle is a series of reactions at complex III where reduced cytochrome c receives electrons from QH2. This process involves electron transfer between cytochrome b and cytochrome c subunits. Antimycin A, an antibiotic, blocks this cycle by interfering with the ubiquinone binding site, halting electron transport.

Oligomycin, an antibiotic, binds to and blocks the proton channel of ATP synthase, preventing protons from flowing through the enzyme. Without proton flow, the rotary motion needed for ATP synthesis cannot occur, stopping the conversion of ADP to ATP despite an active electron transport chain.