How much do you know about the Electron Transport Chain and its inhibitors?

Study Notes

Class materials are for exclusive use of students in the Jerry M. Wallace School of Osteopathic Medicine and have conditions for access and use.
The Electron Transport Chain (ETC) is a series of oxidation reactions that yield CO2 and H2O and ultimately transfer energy to NADH and FADH2.
The ETC is present on the inner mitochondrial membrane and is the common pathway by which different fuels of the body flow to oxygen.
The ETC is composed of five separate protein complexes, and each complex accepts or donates electrons to relatively mobile electron carriers such as coenzyme Q and cytochrome c.
The transfer of electrons down the ETC is driven because NADH is a strong electron donor, and O2 is a strong electron acceptor.
The chemiosmotic hypothesis states that the reaction is coupled to the pumping of protons across the inner mitochondrial membrane to the intermembrane space, creating an electrical and pH gradient that drives ATP synthesis.
ATP synthase catalyzes ATP synthesis by allowing protons to flow back through its Fo domain driven by the gradient, which drives the rotation of the F1 domain.
ETC inhibitors will prevent the flow of electrons through the ETC, causing anaerobic glycolysis in tissues that are affected.
Amytal and rotenone interfere with Complex I of the ETC, while antimycin A interferes with Complex III.
Defects in mitochondrial DNA affect the ETC, and tissues that are highly aerobic (heart, brain) will be affected the most severely.
The Electron Transport Chain (ETC) is a series of proteins in the inner mitochondrial membrane that generates ATP.
ETC inhibitors such as rotenone, antimycin A, cyanide, carbon monoxide, sodium azide, and oligomycin can disrupt ATP synthesis.
Uncoupling proteins (UCPs) allow protons to flow back into the matrix without forming ATP, releasing energy as heat.
Synthetic uncouplers, such as 2,4-dinitrophenol and aspirin, can also uncouple the ETC from ATP synthesis.
Mutations in mitochondrial DNA can cause oxidative phosphorylation defects, affecting highly aerobic tissues such as the nerves and muscles.
Diseases caused by mitochondrial DNA mutations include Leber Hereditary Optic Neuropathy, Myoclonic Epilepsy with Ragged Red Fibers, and Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes.
Leigh syndrome can also result from mutations in mtDNA or nuclear DNA.
The mtDNA has a high mutation rate compared to nuclear DNA due to the generation of ROS in the mitochondria.
Oligomycin is used mainly as a tool to study electron transport in the lab, and the “o” from Fo was named based on this drug.
Brown fat, which contains UCP1, is only found in significant levels in humans in newborns.