MCAT Biochemistry
Oxidative phosphorylation is the metabolic process of making ATP using energy obtained from the transfer of electrons in the electron transport chain. This process takes place in the mitochondria and consists of several components, including complex 1, complex 2, CoQ, complex 3, cytochrome c, complex 4, and ATP synthase. NADH and FADH2 electrons move along the electron transport chain while protons are transported to the intermembrane space, creating an electrochemical gradient. ATP synthase harnesses the energy from the gradient to make ATP in a process called chemiosmosis. Molecular oxygen serves as the final destination for electrons and is converted to water in this process.
There are various toxic agents that can disrupt oxidative phosphorylation and ATP synthesis. Electron transport chain inhibitors block ATP synthesis by reducing the electrochemical gradient, such as rotenone, antimycin A, carbon monoxide, cyanide, and azide drugs. Oligomycin directly inhibits ATP synthase. On the other hand, uncoupling agents increase the permeability of the inner mitochondrial membrane, allowing protons to prematurely travel down their gradient. This reduces the gradient, ATP synthesis, and generates heat while increasing oxygen consumption. Examples of uncoupling agents include 2,4-dinitrophenol, aspirin, and thermogenin.
Lesson Outline
<ul> <li>Oxidative phosphorylation & electron transport chain introduction <ul> <li>Metabolic process of making ATP using energy from electron transport</li> <li>Takes place in mitochondria</li> </ul> </li> <li>Electron transport chain <ul> <li>Consists of complex 1, complex 2, CoQ, complex 3, cytochrome c, complex 4, and ATP synthase</li> <li>NADH and FADH2 electrons move along the chain</li> <li>Protons are transported to the intermembrane space, creating an electrochemical gradient</li> </ul> </li> <li>Oxidative phosphorylation <ul> <li>ATP synthase uses energy from protons traveling down their gradient to make ATP</li> <li>Oxygen accepts electrons to make water</li> </ul> <li>Electron transport chain inhibitors <ul> <li>Block ATP synthesis by preventing electron flow across the electron transport chain</li> <li>Examples: rotenone (inhibits complex I), antimycin A (inhibits complex III), carbon monoxide (inhibits complex IV), cyanide (inhibits complex IV), and azide (inhibits complex IV) drugs</li> </ul> </li> <li>Oligomycin <ul> <li>Directly inhibits ATP synthase</li> </ul> </li> <li>Uncoupling agents <ul> <li>Make the inner mitochondrial membrane more permeable</li> <li>Reduce gradient, reduce ATP synthesis, generate heat, and increase oxygen consumption</li> <li>Examples: 2,4-dinitrophenol, aspirin, and thermogenin</li> </ul> </li> </ul>
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FAQs
The electron transport chain (ETC) is a series of protein complexes and electron carriers located in the mitochondrial membrane. It plays a crucial role in aerobic metabolism, as it facilitates the transfer of electrons from the reduced molecules NADH and FADH2 to oxygen. This process releases energy which is used to pump protons across the mitochondrial membrane, creating a proton gradient. Oxidative phosphorylation then uses the energy from this proton gradient to drive the phosphorylation of ADP to ATP by ATP synthase. The ETC and oxidative phosphorylation together constitute the final stages of aerobic metabolism, and are responsible for the majority of ATP generation in cells.
The electron transport chain consists of four protein complexes (Complex I-IV) and two electron carriers (coenzyme Q and cytochrome c) embedded in the mitochondrial membrane. The main steps in the ETC include: (1) Transfer of electrons from NADH to Complex I, or from FADH2 to Complex II. (2) Transfer of electrons through the complexes, which releases energy used to pump protons across the mitochondrial membrane from the matrix to the intermembrane space. (3) Transfer of electrons to oxygen which forms water, with the help of Complex IV. (4) Establishment of a proton gradient using the energy from the prior steps. The proton gradient is then used to drive protons back into the matrix through the ATP synthase complex, driving ATP production in a process called chemiosmosis.
ATP synthase is a large enzyme complex located in the mitochondrial membrane. It harnesses the proton gradient created by the electron transport chain to synthesize ATP. As protons flow down the gradient, back into the mitochondrial matrix, they pass through a channel in ATP synthase, causing it to rotate. This rotational energy leads to conformational changes in the complex, allowing it to catalyze the phosphorylation of ADP to form ATP. This process of utilizing the proton gradient to generate ATP is called chemiosmosis.
Oxygen plays a crucial role in the electron transport chain as the final electron acceptor. Electrons are passed through the protein complexes, finally reaching Complex IV where they are transferred to molecular oxygen. Oxygen then accepts the electrons and combines with protons to form water. This final transfer ensures the continuous flow of electrons through the ETC, which maintains the proton gradient that drives ATP synthesis through oxidative phosphorylation.
Uncoupling agents are molecules or compounds that disrupt the coupling between the electron transport chain and oxidative phosphorylation. They increase the permeability of the mitochondrial membrane to protons, allowing them to flow back into the mitochondrial matrix without passing through ATP synthase. This uncoupling of the proton gradient from ATP synthesis reduces the efficiency of oxidative phosphorylation, resulting in less ATP production. However, the electron transport chain continues to function, and the energy that would have been used for ATP synthesis is instead released as heat.
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