19.9:
The Electron Transport Chain
The electron transport chain or ETC is the final stage of cellular respiration, where NADH and FADH2 begin a series of redox reactions.
At complex I, NADH donates two electrons across different electron acceptors, reducing Q to QH2.
At complex II, FADH2 transfers electrons via Fe-S to a Q-molecule, forming another QH2.
The QH2 generated in these reactions then diffuse to complex III and transfer electrons to cytochrome c via a series of reactions called the Q cycle.
The reduced cytochrome c moves to complex IV, where after a series of electron transfers, oxygen accepts electrons and combines with protons to produce water.
As electrons pass through complexes I, III, and IV, the energy released is used to pump protons into the intermembrane space.
The pumped protons can then flow down their concentration gradient and activate complex V or ATP synthase to produce ATP from ADP and inorganic phosphate.
Overall, the ETC produces 32 ATP molecules from one molecule of glucose, making it the major energy contributing stage of cellular respiration.
19.9:
The Electron Transport Chain
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in complex I by blocking the Q-binding site. Inhibition of complex I function results in the increased production of reactive oxygen species or ROS. This rotenone-induced ROS production can be detrimental to mitochondrial components, including mitochondrial DNA, and can eventually lead to cell death.
Another competitive inhibitor of ubiquinone is carboxin, a potent fungicide that interferes with the Q-binding site on complex II. The binding of carboxin inhibits the transfer of electrons from FADH2 to ubiquinone, thus blocking the respiratory chain.
Certain antibiotics are also known to inhibit the respiratory chain complexes. For instance, antimycin A, an antibiotic produced by Streptomyces species, interferes with the ubiquinone binding site of complex III, thereby blocking the Q-cycle. The absence of Q-cycle prevents electron transfer between complex III subunits, cytochrome b and cytochrome c, thus inhibiting the electron transport chain.
Sometimes, toxins generated during metabolic activities of the cell can act as an inhibitor of mitochondrial function. For example, carbon monoxide, a by-product of heme catabolism, inhibits complex IV by competing with oxygen for the oxygen-binding sites. This leads to electron accumulation at complex III and results in the generation of superoxide radicals.
The mitochondrial ATP synthase, or complex V, is inhibited by oligomycin, an antibiotic that binds and inhibits its proton channel. This inhibition prevents proton flow through the ATP synthase, thus preventing the rotary motion of the complex needed for catalytic conversion of ADP to ATP.
While these toxins are potent inhibitors of respiratory functions, they can also act as valuable agents in studying individual complexes and enzyme kinetic research.
Suggested Reading
- Ahmad, Maria, Adam Wolberg, and Chadi I. Kahwaji. "Biochemistry, electron transport chain." In StatPearls [Internet]. StatPearls Publishing, 2020.
- Ramsay, Rona R. "Electron carriers and energy conservation in mitochondrial respiration." ChemTexts 5, no. 2 (2019): 1-14.