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Oxidative Phosphorylation

Oxidative Phosphorylation. General Considerations. How do we define oxidative phosphorylation? formation of ATP using the energy released by the transfer of electrons from NADH and FADH 2 through a series of electron carriers What couples the formation of ATP to the transfer of electrons?

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Oxidative Phosphorylation

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  1. Oxidative Phosphorylation

  2. General Considerations • How do we define oxidative phosphorylation? • formation of ATP using the energy released by the transfer of electrons from NADH and FADH2 through a series of electron carriers • What couples the formation of ATP to the transfer of electrons? • a proton gradient

  3. General Considerations • Where in the cell does oxidative phosphorylation take place? • inner mitocondrial membrane • What do we know about the mitocondrial membranes? • outer membrane – reasonably permeable • contains porins – VDAC • inner membrane – relatively impermeable

  4. Origin of Mitocondria • What is the believed origin of mitocondria? • endosymbiosis • What evidence supports this idea? • mitcondrial DNA • machinery for transcription and translation • similarity of genome to bacteria

  5. Redox Potentials and Free Energy Changes • How does one determine the redox potential of a substance? standard reference half-cell sample half-cell

  6. Redox Potentials and Free Energy Changes • What is the relationship between change in redox potential and change in free energy? • G01 = -nF E10 • n = number of electrons transferred • F =faraday (constant, 23.06 kcal/mole/volt) • Can calculate free energy change from reduction potentials of the reactants • By knowing the electron transfer potential of NADH relative to O2 one can calculate the amount of free energy released when O2 is reduced by NADH.

  7. Redox Potentials and Free Energy Changes • One can also quantify the energy associated with a proton gradient. • G = RTln(c2/c1) + ZF V • c2 = concentration on one side of membrane • c1 = concenetration on other side of membrane • Z = electrical charge of transported material • F = Faraday constant (23.06 kcal/mole/volt)

  8. Electron Transport • What determines the rate of electron transport? • distance between donor and acceptor

  9. Electron Transport • driving force or free energy change

  10. Electron Transport • What are the complexes making up the respiratory chain? • three proton pumps • one link to citric acid cycle

  11. Electron Transport • What is the role of ubiquinone or coenzyme Q?

  12. Electron Transport • What happens to the electrons from NADH? • enter ETS at NADH-Q oxidoreductase

  13. Electron Transport • Initial step is transfer of electrons to FMN a prosthetic group of the enzyme

  14. Electron Transport • Electrons are then transferred to iron-sulfur clusters another prosthetic group

  15. Electron Transport • Electrons from clusters transferred to coenzyme Q • as a result of electron transfer four protons are pumped out of mitocondrial matrix • Reaction summarized: • NADH + Q + 5H+matrix  NAD+ + QH2 + 4H+cytosol

  16. Electron Transport • Coenzyme Q also serves as entry point for electrons from FADH2 from oxidation of succinate • succinate-Q reductase complex • inner mitocondrial membrane • FADH2 transfers electrons to iron-sulfur clusters then to Q • no protons are pumped

  17. Electron Transport • Q-cytochrome c oxidoreductase catalyzes the transfer of electrons from Q to cytochrome c • What is a cytochrome? • electron transferring protein with heme prosthetic group • transfers only electrons • iron in heme goes between Fe+2 and Fe+3

  18. Electron Transport • Q-cytochrome c oxidoreductase contains 3 hemes and a iron-sulfur cluster

  19. Electron Transport • What is the Q cycle? • mechanism of coupling of electron transfer from Q to cytochrome c to proton transport

  20. Electron Transport • What is the function of cytochrome c oxidase? • reduction of oxygen to water • What are the major prosthetic groups of this complex? • CuA/CuA • heme a • heme a3-Cub

  21. Cytochrome c Oxidase

  22. Cytochrome c Oxidase • Mechanism of action

  23. Cytochrome c Oxidase • cytochrome c oxidase pumps four additional protons from matrix for a total of eight protons removed from matrix

  24. Electron Transport System

  25. Electron Transport System

  26. Electron Transport • Toxic derivatives of molecular oxygen may be formed by partial reduction O2 O2_  O2_2 superoxide anion peroxide

  27. Electron Transport • How does the cell protect itself against these reactive oxygen species? • makes use of superoxide dismutase and catalase • 2O2_ + 2H+  O 2 + H2O2 • 2H2O2  O2 + 2H2O

  28. ATP Synthesis • What is the chemiosmotic hypothesis? • ATP synthesis and electron transport are coupled by proton gradient across mitocondrial membrane

  29. ATP Synthesis • What is ATP synthase and what do we know about its structure? • consists of F1 and F0 • F1 has 5 types of polypeptide chains • 3,3,,, • F0 contains proton channel • 10-14 c subunits • a,b2 subunits

  30. ATP Synthesis • How is ATP synthesized?

  31. ATP Synthesis • What is the role of the proton gradient in ATP synthesis? • part of binding-change mechansm • 3  subunits promote ADP & P binding, ATP synthesis, ATP release

  32. ATP Synthesis • How does proton flow through F0 drive the rotation of the  subunit? • each c subunits consists of 2  helices with one helix containing an aspartic acid residue • a subunit contains two proton half channels

  33. ATP Synthesis • Proton enters half-channel, neutralizes charge on aspartate • c can rotate clockwise • proton can move into matrix

  34. ATP Synthesis • Since c ring is linked to  and  subunits, as c turns these subunits rotate • rotation protmotes synthesis of ATP via binding-change mechanism • each 3600 rotation of  subunit leads to synthesis of 3 ATP’s • 10 protons generate 3 ATP’s • each ATP requires transport of about 3 protons

  35. Mitocondrial Shuttles • Reoxidation of cytosolic NADH requires shuttle mechanism • glycerol 3-phosphate shuttle • found in muscle

  36. Mitocondrial Shuttles • malate-aspartate shuttle • heart and liver

  37. Mitocondrial Shuttles • What is an ATP-ADP translocase? • transport protein allowing ATP to exit mitocondrion and ADP to enter • result in moving one negative charge out of matrix • decreases proton motive force

  38. Mitocondrial Shuttles • Other mitocondrial transport proteins act as shuttles

  39. Regulation of Respiration • Energy formed from oxidation of glucose • 3 protons = 1 ATP • 1 proton used to move ATP • one pair of electons from NADH = 2.5 molecules of ATP

  40. Regulation of Respiration • What controls rate of electron transport?

  41. Regulation of Respiration • Oxidative phosphorylation can be inhibited by many substances

  42. Regulation of Respiration • What are uncoupling agents? • transport protons across mitocondrial membrane

  43. Regulation of Respiration • Does uncoupling serve any useful purpose? • body heat generation

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