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Oxidative Phosphorylation

Oxidative phosphorylation (OXPHOS) is an essential part of cellular respiration and is the primary metabolic pathway through which cells produce ATP, their main energy molecule. In the mitochondria, OXPHOS utilizes an electron transport chain and a proton gradient to convert ADP into ATP.

Oxidative Phosphorylation

Pathway Summary

Oxidative phosphorylation is the production of ATP using energy derived from the transfer of electrons in an electron transport system and occurs by chemiosmosis. The process is accomplished though oxidation-reduction reactions in the mitochondria. During oxidative phosphorylation, electrons are transferred from electron donors to electron acceptors, referred to as the electron transport chain. The flow of electrons from NADH to O2 through protein complexes located in the mitochondrial inner membrane leads to the pumping of protons out of the mitochondrial matrix. The resulting uneven distribution of protons generates a pH gradient and a transmembrane electrical potential that creates a proton-motive force. ATP is synthesized when protons flow back to the mitochondrial matrix through an enzyme complex (Complex V). The oxidation of fuels and the phosphorylation of ADP are coupled by the proton gradient across the inner mitochondrial membrane.Oxidative phosphorylation consists of five protein-lipid enzyme complexes (Complex I - V) located in the mitochondrial inner membrane that contain flavins (FMN, FAD), quinoid compounds (coenzyme Q10, CoQ10) and transition metal compounds (iron-sulfur clusters, hemes, protein-bound copper). These enzymes are designated complex I (NADH:ubiquinone oxidoreductase, EC 1.6. 5.3), complex II (succinate:ubiquinone oxidoreductase, EC 1.3.5.1), complex III (ubiquinol:ferrocytochrome c oxidoreductase, EC 1.10.2.2), complex IV (ferrocytochrome c:oxygen oxidoreductase or cytochrome c oxidase, EC 1.9.3.1), and complex V (ATP synthase, EC 3.6.1.34). Complex I transports electrons from NADH to ubiquinone. Complex II catalyzes the oxidation of succinate to fumarate and transfers electrons to ubiquinone pool of respiratory chain. Complex III transfers electrons from ubiquinol to cytochrome c coupled with the transfer of electrons across inner mitochondrial membrane. Complex IV, the final step in the electron transport chain, is the reduction of molecular oxygen by electrons derived from cytochrome c. Complex V, the final enzyme in the oxidative phosphorylation pathway, couples a proton gradient generated by respiratory chain to ATP synthesis where protons flow from intermembrane mitochondrial space to the matrix.

Oxidative Phosphorylation Genes list

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Frequently Asked Questions

What is oxidative phosphorylation (OXPHOS)?

Oxidative phosphorylation, often abbreviated as OXPHOS, is a vital metabolic process that occurs in the mitochondria. It's responsible for producing ATP (adenosine triphosphate), the primary energy molecule for cells, by using an electron transport chain and a proton gradient.

Where does oxidative phosphorylation take place in the cell?
Oxidative phosphorylation primarily takes place in the mitochondria, specifically within the inner mitochondrial membrane. The mitochondria are often referred to as the powerhouses of the cell due to their role in energy production.
How is oxidative phosphorylation related to cellular respiration?
Oxidative phosphorylation is the final stage of cellular respiration. It follows the processes of glycolysis and the citric acid cycle, converting the energy from nutrient molecules into ATP.
What is the role of the electron transport chain in oxidative phosphorylation?
The electron transport chain is a series of protein complexes that transfer electrons from donors to acceptors. This transfer creates a proton gradient across the inner mitochondrial membrane, which is essential for ATP synthesis.
How does the proton gradient contribute to ATP production?
The proton gradient that is established by the electron transport chain provides the necessary energy for a protein called ATP synthase. As protons flow back into the mitochondrial matrix, ATP synthase uses this energy to convert ADP (adenosine diphosphate) and inorganic phosphate into ATP.
Why is oxygen crucial for oxidative phosphorylation?
Oxygen serves as the final electron acceptor in the electron transport chain. It accepts electrons and combines with protons to form water. This step is essential because it ensures that electrons move efficiently through the chain instead of building up and disrupting the energy production process.
How is oxidative phosphorylation regulated within the cell?
Oxidative phosphorylation is intricately regulated by multiple mechanisms to ensure optimal energy production. Feedback loops play a crucial role, where the abundance or scarcity of certain molecules can either promote or inhibit parts of the OXPHOS pathway. In addition, the availability of substrates like NADH (nicotinamide adenine dinucleotide) and FADH2 (flavin adenine dinucleotide) can influence the rate of ATP production. Furthermore, post-translational modifications can activate or deactivate specific components of the OXPHOS system.
Which diseases or conditions are associated with oxidative phosphorylation dysfunction?
Oxidative phosphorylation dysfunction is connected to a variety of health challenges. When the process doesn’t function optimally, cells struggle to produce the energy they require, leading to cellular distress and potential damage. This is evident in neurodegenerative diseases like Parkinson's and Alzheimer's, where the energy-intensive brain cells are compromised. Metabolic disorders, such as mitochondrial myopathies, emerge when muscle cells can't generate enough energy. Furthermore, certain cancers have been found to exhibit changes in OXPHOS activity, which can impact tumor growth and resistance to treatments.
How do cancer cells utilize oxidative phosphorylation?
Many cancer cells, such as those in aggressive forms like glioblastoma or pancreatic cancer, are characterized by increased glycolysis (known as the Warburg effect), but they don't abandon oxidative phosphorylation entirely. Certain cancers, including breast and ovarian cancers, have been observed to retain or even enhance their OXPHOS capabilities under specific conditions. This metabolic flexibility allows them to adapt and thrive in various tumor microenvironments, providing them with a distinct metabolic advantage.
How is oxidative phosphorylation linked to other metabolic pathways?
Oxidative phosphorylation is closely intertwined with metabolic pathways like glycolysis and the citric acid cycle. Glycolysis breaks down glucose to pyruvate, which feeds into the citric acid cycle, generating electron carriers for OXPHOS. Additionally, during low carbohydrate conditions, the body breaks down fats via fatty acid oxidation, producing molecules that also support the citric acid cycle. These integrated pathways ensure consistent energy supply for the cell, adapting to different nutrient sources.

Energy Generation through Oxidative Phosphorylation