7.4 Oxidative Phosphorylation

3 min readjune 14, 2024

The and are crucial processes in cellular energy production. They involve the movement of electrons through protein complexes, creating a across the .

This gradient drives ATP synthesis through , a process explained by Mitchell's theory. The coupling of electron transport to proton pumping and ATP production allows cells to efficiently convert energy from nutrients into usable ATP molecules.

Electron Transport Chain and Oxidative Phosphorylation

Movement of electrons in transport chain

  • Electrons enter electron transport chain (ETC) from and produced during and
  • ETC consists of protein complexes (I, II, III, IV) embedded in inner mitochondrial membrane
    • () accepts electrons from NADH passes them to (Q)
    • () accepts electrons from FADH2 also passes them to
    • Ubiquinone carries electrons to ()
    • Complex III passes electrons to , mobile electron carrier
    • Cytochrome c transfers electrons to ()
  • As electrons move through ETC, they lose energy in stepwise manner
    • Energy used to pump protons (H+) from into creating proton gradient
  • At Complex IV, electrons finally transferred to oxygen (O2), terminal electron acceptor forming water (H2O)
  • ETC involves a series of , where electrons are transferred from one molecule to another

Creation of proton gradient

  • Proton gradient established by pumping protons (H+) from mitochondrial matrix into intermembrane space
  • Complexes I, III, IV of ETC actively transport protons across inner mitochondrial membrane (acting as proton pumps)
    • Complex I pumps 4 H+ for every 2 electrons transferred from NADH
    • Complex III pumps 4 H+ for every 2 electrons transferred from ubiquinone
    • Complex IV pumps 2 H+ for every 2 electrons transferred from cytochrome c
  • Inner mitochondrial membrane impermeable to protons allowing gradient to be maintained
  • Proton gradient creates electrochemical potential known as consisting of:
    • Chemical gradient (higher concentration of H+ in intermembrane space)
    • Electrical gradient (intermembrane space becomes positively charged relative to matrix)
  • Proton motive force used to drive ATP synthesis through chemiosmosis

ATP production through chemiosmosis

  • enzyme complex located in inner mitochondrial membrane
  • Consists of two main components:
    • (proton channel): allows protons to flow down electrochemical gradient from intermembrane space to matrix
    • (catalytic unit): catalyzes synthesis of ATP from and inorganic phosphate (Pi)
  • Protons flow through F0 component driven by proton motive force
  • Flow of protons causes rotation of in F0 component connected to of F1 component
  • Rotation of γ-subunit induces conformational changes in of F1 component
    • Conformational changes cycle β-subunits through three states: open, loose, tight
      1. In open state, ADP and Pi bind to β-subunit
      2. In tight state, ADP and Pi condensed to form ATP
      3. In loose state, ATP released from β-subunit
  • For each complete rotation of γ-subunit (360°), 3 ATP molecules synthesized
  • Process of using proton gradient to drive ATP synthesis called chemiosmosis

Chemiosmotic Theory and Coupling

  • explains how the proton gradient is used to drive ATP synthesis
  • refers to the link between electron transport and ATP production
    • Electron transport in the ETC is coupled to proton pumping
    • Proton flow through ATP synthase is coupled to ATP synthesis

Key Terms to Review (38)

ADP: ADP, or adenosine diphosphate, is a nucleotide that plays a crucial role in cellular energy transfer. It is formed when ATP (adenosine triphosphate) loses one of its phosphate groups, releasing energy that can be used for various biological processes. This transformation links ADP to the concepts of energy production, metabolism, and the regulation of biochemical pathways.
ATP synthase: ATP synthase is an essential enzyme complex located in the inner mitochondrial membrane and thylakoid membranes of chloroplasts, responsible for synthesizing adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate (Pi). It connects the processes of cellular respiration and photosynthesis by using the proton gradient generated from electron transport chains to drive ATP production, which is vital for energy transfer in living organisms.
C-ring: The c-ring is a component of ATP synthase, an enzyme complex crucial for oxidative phosphorylation. This ring structure is embedded within the inner mitochondrial membrane and plays a vital role in the production of adenosine triphosphate (ATP) by utilizing the proton gradient generated by the electron transport chain. The rotation of the c-ring, driven by protons flowing through it, leads to conformational changes in ATP synthase that ultimately facilitate ATP synthesis.
Chemiosmosis: Chemiosmosis is the process by which ions, particularly protons (H+), are transported across a selectively permeable membrane, generating ATP through ATP synthase in both cellular respiration and photosynthesis. This mechanism is crucial for energy production as it harnesses the energy from the movement of protons down their electrochemical gradient, driving the synthesis of adenosine triphosphate (ATP). It links the electron transport chain to ATP production in mitochondria during cellular respiration and thylakoid membranes during photosynthesis.
Citric acid cycle: The citric acid cycle, also known as the Krebs cycle or TCA cycle, is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. It takes place in the mitochondria and produces high-energy molecules such as NADH and FADH2.
Citric acid cycle: The citric acid cycle, also known as the Krebs cycle or TCA cycle, is a crucial metabolic pathway that plays a key role in the cellular respiration process by converting acetyl-CoA into carbon dioxide while generating energy-rich molecules like ATP, NADH, and FADH2. This cycle is essential for energy production in aerobic organisms and connects various metabolic pathways, including carbohydrate, protein, and lipid metabolism.
Complex I: Complex I, also known as NADH:ubiquinone oxidoreductase, is the first enzyme complex in the electron transport chain of cellular respiration, responsible for transferring electrons from NADH to ubiquinone (coenzyme Q). This transfer is coupled with the pumping of protons from the mitochondrial matrix into the intermembrane space, contributing to the proton gradient essential for ATP synthesis during oxidative phosphorylation.
Complex II: Complex II, also known as succinate dehydrogenase, is a crucial component of the electron transport chain located in the inner mitochondrial membrane. It plays a dual role in cellular respiration by participating in both the citric acid cycle and oxidative phosphorylation, facilitating the transfer of electrons from succinate to coenzyme Q (ubiquinone). This process contributes to the generation of a proton gradient across the membrane, which is essential for ATP synthesis.
Complex III: Complex III, also known as the cytochrome bc1 complex, is a crucial component of the electron transport chain located in the inner mitochondrial membrane. It plays a vital role in oxidative phosphorylation by facilitating the transfer of electrons from ubiquinol (QH2) to cytochrome c, while simultaneously pumping protons (H+) across the membrane to create a proton gradient. This gradient is essential for ATP synthesis during cellular respiration.
Complex IV: Complex IV, also known as cytochrome c oxidase, is the final enzyme in the electron transport chain of cellular respiration. It plays a crucial role in oxidative phosphorylation by catalyzing the transfer of electrons from cytochrome c to molecular oxygen, resulting in the reduction of oxygen to water. This complex not only facilitates the final steps of electron transport but also contributes to the proton gradient that drives ATP synthesis.
Cytochrome bc1 complex: The cytochrome bc1 complex is a crucial protein complex located in the inner mitochondrial membrane, playing a key role in cellular respiration and energy production. This complex functions as an electron transport chain component, facilitating the transfer of electrons from ubiquinol to cytochrome c while simultaneously pumping protons across the membrane to create an electrochemical gradient. This gradient is essential for ATP synthesis, linking electron transport to oxidative phosphorylation.
Cytochrome c: Cytochrome c is a small heme protein found loosely associated with the inner membrane of the mitochondria, playing a crucial role in the electron transport chain during cellular respiration. It acts as an electron carrier, transferring electrons between complexes III and IV, which is essential for the production of ATP through oxidative phosphorylation. Additionally, cytochrome c is involved in apoptotic signaling pathways, linking cellular respiration with cell death mechanisms.
Cytochrome c oxidase: Cytochrome c oxidase is an essential enzyme in the electron transport chain that catalyzes the transfer of electrons from cytochrome c to molecular oxygen, leading to the reduction of oxygen to water. This process plays a crucial role in cellular respiration by driving the synthesis of ATP through oxidative phosphorylation, linking electron transport to proton gradient formation across the inner mitochondrial membrane.
Electron transport chain: The electron transport chain (ETC) is a series of protein complexes and other molecules located in the inner mitochondrial membrane that transfer electrons from electron donors to electron acceptors via redox reactions, ultimately generating adenosine triphosphate (ATP) through oxidative phosphorylation. It plays a critical role in energy metabolism and cellular respiration, connecting various metabolic processes.
F0: F0 is a protein complex found in the inner mitochondrial membrane that plays a crucial role in ATP synthesis during oxidative phosphorylation. It functions as a part of the ATP synthase enzyme, where protons flow through F0 to drive the conversion of ADP and inorganic phosphate into ATP. This process is vital for cellular energy production and is tightly coupled with electron transport and proton gradient generation.
F1: F1 refers to the ATP synthase enzyme's F1 component, which is responsible for synthesizing ATP from ADP and inorganic phosphate during oxidative phosphorylation. This process takes place in the mitochondria and is crucial for energy production in cells, linking the electron transport chain to ATP generation.
FADH2: FADH2 is a reduced form of flavin adenine dinucleotide, a crucial electron carrier in cellular respiration. It plays a key role in transferring electrons from metabolic substrates to the electron transport chain, contributing to ATP production through oxidative phosphorylation. This process is integral for energy metabolism, linking the breakdown of carbohydrates, proteins, and lipids to energy generation.
Glycolysis: Glycolysis is the metabolic pathway that converts glucose into pyruvate, releasing energy and producing ATP. It takes place in the cytoplasm of the cell and does not require oxygen.
Glycolysis: Glycolysis is a metabolic pathway that converts glucose into pyruvate, generating small amounts of energy in the form of ATP and NADH. This process occurs in the cytoplasm of cells and serves as a fundamental step in cellular respiration, connecting carbohydrate metabolism with energy production.
Inner mitochondrial membrane: The inner mitochondrial membrane is a highly specialized lipid bilayer that encloses the mitochondrion's matrix, playing a crucial role in cellular respiration and energy production. It contains a variety of proteins essential for the electron transport chain and ATP synthesis, making it a vital component in the process of oxidative phosphorylation. Its unique structure, including numerous folds called cristae, increases the surface area available for these biochemical processes.
Intermembrane space: The intermembrane space is the region between the inner and outer membranes of mitochondria. This space plays a crucial role in cellular respiration, particularly during oxidative phosphorylation, where it becomes a key area for proton accumulation and electrochemical gradients that drive ATP production.
Mitchell's chemiosmotic theory: Mitchell's chemiosmotic theory proposes that ATP (adenosine triphosphate) is generated through the movement of protons across a membrane, creating a proton gradient that drives the synthesis of ATP via ATP synthase. This process is fundamental in cellular respiration and photosynthesis, highlighting the importance of membrane potential in energy conversion.
Mitochondrial matrix: The mitochondrial matrix is the innermost compartment of a mitochondrion, enclosed by the inner mitochondrial membrane. It plays a crucial role in cellular respiration, containing enzymes for the citric acid cycle, as well as the mitochondrial DNA and ribosomes necessary for protein synthesis. This environment is essential for the oxidation of pyruvate and the production of ATP through oxidative phosphorylation.
NADH: NADH, or nicotinamide adenine dinucleotide (reduced form), is a crucial coenzyme in cellular metabolism that carries electrons and plays a key role in energy production. It acts as an electron donor in various metabolic pathways, enabling the conversion of food into energy and facilitating oxidative phosphorylation, glycolysis, and the citric acid cycle.
NADH dehydrogenase: NADH dehydrogenase is an enzyme that plays a crucial role in the electron transport chain by facilitating the transfer of electrons from NADH to ubiquinone (coenzyme Q). This process not only helps in regenerating NAD+ for glycolysis and the citric acid cycle but also contributes to the creation of a proton gradient across the inner mitochondrial membrane, which is essential for ATP synthesis during oxidative phosphorylation.
Oxidative phosphorylation: Oxidative phosphorylation is the final stage of cellular respiration where ATP is produced through the electron transport chain and chemiosmosis. This process involves the transfer of electrons from NADH and FADH2 to oxygen, creating a proton gradient that drives ATP synthesis in mitochondria.
Oxidative Phosphorylation Coupling: Oxidative phosphorylation coupling refers to the process where the energy released from the electron transport chain is used to drive the synthesis of ATP through chemiosmosis in mitochondria. This coupling is vital for cellular respiration, as it links the oxidation of nutrients with the phosphorylation of ADP to produce ATP, essentially functioning as the final step in energy production within cells.
Prosthetic group: A prosthetic group is a non-protein molecule that is tightly and permanently attached to a protein, aiding its function. These groups are essential for the biological activity of certain proteins, particularly enzymes.
Proton gradient: A proton gradient is an electrochemical gradient formed by the difference in proton concentration across a membrane, which is essential for energy production in cells. This gradient is created during processes like cellular respiration and photosynthesis, where protons are pumped from one side of a membrane to another, generating potential energy that drives ATP synthesis through ATP synthase.
Proton Motive Force: Proton motive force (PMF) refers to the electrochemical gradient generated across a membrane, driven by the movement of protons (H\^+) from one side of the membrane to the other. This force is crucial in oxidative phosphorylation as it provides the energy needed for ATP synthesis, linking electron transport with ATP production in cellular respiration.
Proton Pump: A proton pump is a type of active transport mechanism found in cell membranes that moves protons (H+ ions) across the membrane against their concentration gradient, using energy from ATP hydrolysis. This process is essential for various cellular functions, including generating a proton gradient that drives ATP synthesis in cellular respiration and maintaining pH balance in cells.
Redox reactions: Redox reactions, or oxidation-reduction reactions, involve the transfer of electrons between molecules. These reactions are crucial for energy transfer in biological systems.
Redox reactions: Redox reactions, or reduction-oxidation reactions, are chemical processes that involve the transfer of electrons between two substances. In these reactions, one substance is oxidized, losing electrons, while the other is reduced, gaining electrons. This electron transfer is essential for energy production in living systems, playing a critical role in metabolic pathways and energy conversion processes.
Succinate dehydrogenase: Succinate dehydrogenase is an enzyme that plays a crucial role in the citric acid cycle by catalyzing the conversion of succinate to fumarate, while simultaneously reducing flavin adenine dinucleotide (FAD) to FADH2. This enzyme is unique as it is the only one that participates in both the citric acid cycle and the electron transport chain, bridging these critical metabolic pathways.
Ubiquinone: Ubiquinone, also known as coenzyme Q10, is a lipid-soluble molecule that plays a crucial role in the electron transport chain within mitochondria. It facilitates the transfer of electrons between complex I and complex III, and between complex II and complex III.
Ubiquinone: Ubiquinone, also known as coenzyme Q10, is a vital component of the electron transport chain found in the inner mitochondrial membrane. It serves as a mobile electron carrier that transfers electrons from complex I and complex II to complex III, playing a crucial role in oxidative phosphorylation. By facilitating this transfer, ubiquinone helps create a proton gradient across the mitochondrial membrane, which is essential for ATP synthesis during cellular respiration.
β-subunits: β-subunits are integral components of the ATP synthase complex, playing a critical role in the process of oxidative phosphorylation. These subunits are essential for catalyzing the production of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate (Pi) as protons flow through the ATP synthase enzyme, driven by the proton gradient generated during electron transport.
γ-subunit: The γ-subunit is a crucial component of ATP synthase, an enzyme that plays a key role in oxidative phosphorylation. It acts as a rotational element within the enzyme complex, connecting the catalytic sites where ATP is produced to the proton gradient generated by the electron transport chain. This rotation is essential for synthesizing ATP from ADP and inorganic phosphate.
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