Metabolic: lecture 25
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Questions and Answers

What is necessary for ATP synthesis to occur according to the chemiosmotic hypothesis?

  • A proton gradient across the inner mitochondrial membrane (correct)
  • High concentrations of ATP in the matrix
  • The presence of oxygen
  • An increase in the temperature of the mitochondrial environment

    • Which component is directly involved in the phosphorylation of ADP to form ATP?

  • NADH
  • ATP synthase (correct)
  • Complex I
  • Proton gradient

    • What role do protons play in ATP synthesis according to the chemiosmotic model?

  • They are pumped out of the mitochondrial matrix to create a gradient. (correct)
  • They directly bind to ADP to form ATP.
  • They inhibit ATP synthase and reduce ATP production.
  • They combine with oxygen to release energy.

    • Which of the following is a product of the reaction catalyzed by ATP synthase?

    <p>ATP</p> Signup and view all the answers

    The proton-motive force generated by electron transport is crucial for which of the following?

    <p>Driving the synthesis of ATP</p> Signup and view all the answers

    What is the role of Arg 210 in the mechanism of ATP synthesis?

    <p>It transfers H+ to or from Asp61.</p> Signup and view all the answers

    Which conformational state of the β subunit has the strongest binding to ATP?

    <p>Tight</p> Signup and view all the answers

    Which is the hardest step in ATP synthesis according to the content?

    <p>Forcing the T conformation to release ATP.</p> Signup and view all the answers

    What happens when H+ enters the first half-channel of subunit a?

    <p>It binds to Asp61 of the c subunits.</p> Signup and view all the answers

    How is the ATPase activity characterized in the ATP synthase structure?

    <p>It is localized to the β subunits.</p> Signup and view all the answers

    What does the ‘binding-change’ model for ATP synthase explain?

    <p>How conformational changes facilitate ATP release.</p> Signup and view all the answers

    What is the significance of the asymmetric γ subunit in ATP synthase?

    <p>It applies force to the β subunits as it rotates.</p> Signup and view all the answers

    What is the purpose of the microscopy technique mentioned in the evidence for rotation?

    <p>To monitor the movement of actin filaments.</p> Signup and view all the answers

    Study Notes

    Electron Flow in the Respiratory Chain

    • The respiratory chain is a series of protein complexes embedded in the inner mitochondrial membrane.
    • Electrons are passed from NADH and FADH₂ to oxygen, releasing energy.
    • This energy is used to pump protons (H⁺) from the matrix to the intermembrane space, creating a proton gradient.
    • The proton gradient drives ATP synthesis.
    • Complex I accepts electrons from NADH and pumps protons across the membrane.
    • Complex II accepts electrons from FADH₂ and does not pump protons across the membrane.
    • Complex III accepts electrons from coenzyme Q and pumps protons across the membrane.
    • Complex IV accepts electrons from cytochrome c and pumps protons across the membrane.
    • Oxygen accepts electrons at complex IV to form water.
    • ATP synthesis is coupled to the flow of protons back into the matrix through ATP synthase.

    The Chemiosmotic Hypothesis

    • Proposed by Peter Mitchell in the 1960s.
    • Theory: Electron transport and ATP synthesis are coupled by a proton gradient across the inner mitochondrial membrane.
    • Mitchell's postulates:
      • Intact inner mitochondrial membrane is required.
      • Electron transport through the ETC generates a proton gradient.
      • ATP synthase catalyses phosphorylation of ADP.
      • The reaction is driven by the movement of H⁺ across the IMM into the matrix.

    ATP Hydrolysis and Synthesis

    • ATP hydrolysis is highly favorable (ΔG = -40 to -50 kJ/mol).
    • ATP synthesis requires energy (ΔG = +40 to +50 kJ/mol).
    • The energy for ATP synthesis comes from the proton gradient.
    • Anisotropic distribution of H₂O is essential to drive reaction in the "wrong" direction.
    • Protons must be pumped, creating a gradient.

    Chemiosmotic Model for ATP Synthesis

    • Electron transport sets up a proton-motive force.
    • Energy of the proton-motive force drives ATP synthesis.
    • The proton-motive force is a combination of proton gradient (ΔpH) and membrane potential (Δψ).

    ATP Synthase (Complex V)

    • A large protein complex composed of two parts:
      • F₀: Embedded in the inner mitochondrial membrane. Forms a proton channel.
      • F₁: Projects into the mitochondrial matrix. Catalyses ATP synthesis.
    • ATP synthase is similar to bacterial and plant ATPase.
    • Oligomycin blocks the flow of H⁺ through the Fo channel, inhibiting ATP synthesis.

    Structure and Function of ATP Synthase

    • The components: Stator, rotor, and catalytic subunits (a, b, c, α, ß, γ, δ, ε).
    • F₀ is a hydrophobic H⁺ channel embedded in the inner mitochondrial membrane (subunits a and c).
    • The c-ring of the rotor rotates by the proton flow.
    • 1 H⁺ per c subunit, stoichiometry of H⁺ needed per ATP varies between species.

    Fo Proposed Mechanism

    • Rotation of the c-ring involves coordinated swiveling movements of the c-subunit helix (protonation/deprotonation of Asp61).
    • Arg 210 transfers H⁺ to or from Asp61. .
    • Protons are passed from or to each half-channel of subunit a.

    F₁ Catalyzes ADP+Pi to ATP

    • F₁ catalyzes the synthesis of ATP from ADP and Pi.
    • It has three β-subunits, each in different conformations:
      • Loose: binds ADP and Pi
      • Open: releases ATP
      • Tight: catalyzes ATP formation
    • The conformation changes are driven by rotation of the y subunit.

    The Binding Change Model for ATP Synthase

    • The rotating γ subunit forces the conformational shift of the β-subunits, driving ATP synthesis.
      • L → T → O
    • The "hardest step" is forcing the T conformation to release ATP.
    • The binding pocket drives ATP release.

    Coupling Proton Translocation to ATP Synthesis

    • Proton translocation leads to rotation of the Fo subunit and the central shaft (γ).
    • This induces conformational changes in the F₁ subunits, driving ATP synthesis.

    Transport of ADP and Pi to the Matrix

    • Adenine nucleotide translocase (antiporter) moves ADP into and ATP out of the mitochondrial matrix.
    • Phosphate translocase (symporter) moves Pi into the matrix and H⁺ into the matrix.

    ATP Synthesis Can Be Uncoupled From ETC

    • Uncoupling protein 1 (UCP-1) found in brown adipose tissue (babies and hibernating animals) uncouples proton translocation from ATP synthesis, generating heat instead of ATP.

    Alternative Oxidase (AOX)

    • A CN-resistant respiration, generating heat rather than ATP.

    Thermogenesis

    • Thermogenesis is the production of heat.
    • The Arum spadix flower uses thermogenesis to attract pollinators.

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    ATP Synthase Lecture 25 PDF

    Description

    Test your knowledge on the chemiosmotic hypothesis related to ATP synthesis. This quiz covers the mechanisms of ATP synthase, the role of protons, and the importance of the proton-motive force in cellular respiration. Perfect for students studying biochemistry or cellular biology.

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