Inhibitors
There are several well-known drugs and toxins that inhibit oxidative phosphorylation. Although any one of these toxins inhibits only one enzyme in the electron transport chain, inhibition of any step in this process will halt the rest of the process. For example, if oligomycin inhibits ATP synthase, protons cannot pass back into the mitochondrion. As a result, the proton pumps are unable to operate, as the gradient becomes too strong for them to overcome. NADH is then no longer oxidized and the citric acid cycle ceases to operate because the concentration of NAD+ falls below the concentration that these enzymes can use.
| Compounds | Use | Effect on oxidative phosphorylation |
|---|---|---|
| Cyanide Carbon monoxide Azide |
Poisons | Inhibit the electron transport chain by binding more strongly than oxygen to the Fe–Cu center in cytochrome c oxidase, preventing the reduction of oxygen. |
| Oligomycin | Antibiotic | Inhibits ATP synthase by blocking the flow of protons through the Fo subunit. |
| CCCP 2,4-Dinitrophenol |
Poisons | Ionophores that disrupt the proton gradient by carrying protons across a membrane. This ionophore uncouples proton pumping from ATP synthesis because it carries protons across the inner mitochondrial membrane. |
| Rotenone | Pesticide | Prevents the transfer of electrons from complex I to ubiquinone by blocking the ubiquinone-binding site. |
| Malonate and oxaloacetate | Competitive inhibitors of succinate dehydrogenase (complex II). |
Not all inhibitors of oxidative phosphorylation are toxins. In brown adipose tissue, regulated proton channels called uncoupling proteins can uncouple respiration from ATP synthesis. This rapid respiration produces heat, and is particularly important as a way of maintaining body temperature for hibernating animals, although these proteins may also have a more general function in cells' responses to stress.
Read more about this topic: Oxidative Phosphorylation