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Electron Transport and Oxidative Phosphorylation

Electron Transport and Oxidative Phosphorylation. Dr.sadia haroon Department of biochemistry Peshawar medical college. Mitochondria. outer membrane relatively permeable inner membrane permeable only to those things with specific transporters Impermeable to NADH and FADH 2

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Electron Transport and Oxidative Phosphorylation

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  1. Electron Transport and Oxidative Phosphorylation Dr.sadia haroon Department of biochemistry Peshawar medical college.

  2. Mitochondria • outer membrane relatively permeable • inner membrane permeable only to those things with specific transporters • Impermeable to NADH and FADH2 • Permeable to pyruvate • Compartmentalization • Kreb's and β-oxidation in matrix • Glycolysis in cytosol

  3. Most energy from Redox • electrons during metabolic reactions sent to NAD and FAD • Glycolysis • In cytosol • produces 2 NADH • Pyruvate dehydrogenase reaction • In mitochondrial matrix • 2 NADH / glucose • Krebs • In mitochondrial matrix • 6 NADH and 2 FADH2 / glucose

  4. Electron Transport Chain • Groups of redox proteins • On inner mitochondrial membrane • Binding sites for NADH and FADH2 • On matrix side of membrane • Electrons transferred to redox proteins • NADH reoxidized to NAD+ • FADH2 reoxidized to FAD

  5. 4 Complexes • proteins in specific order • Transfers 2 electrons in specific order • Proteins localized in complexes • Embedded in membrane • Ease of electron transfer • Electrons ultimately reduce oxygen to water • 2 H+ + 2 e- + ½ O2 -- H2O

  6. Electron Transport Chain

  7. Complex 1 • Has NADH binding site • NADH reductase activity • NADH - NAD+ • NADH ---> FMN--->FeS---> ubiquinone • ubiquinone ---> ubiquinone H2 • 4 H+ pumped/NADH

  8. Electron Transport Chain

  9. Complex II • succinate ---FAD—ubiquinone • Contains coenzyme Q • FADH2 binding site • FAD reductase activity • FADH2 -- FAD

  10. Electron Transport Chain

  11. Complex III • ubiquinone - ubiquinone ox • while cyt C gets reduced • Also contains cytochromes b • proton pump 4H+ • Adds to gradient • 8 H+ / NADH • 4 H+ / FADH2

  12. Electron Transport Chain

  13. Complex IV • reduction of oxygen • cytochrome oxidase • cyt a+a3 red ---> oxidized state • oxygen ---> water • 2 H+ + 2 e- + ½ O2 -- 2 H2O • transfers e- one at a time to oxygen • Pumps 2H+ out • Total of 10 H+ / NADH • Total of 6 H+ / FADH2

  14. Totals • Proton gradient created as electrons transferred to oxygen forming water • 10 H+ / NADH • 6 H+ / FADH2

  15. Electron Transport Chain

  16. Generation of ATP • Proton dependant ATP synthetase • Uses proton gradient to make ATP • Protons pumped through channel on enzyme • From intermembrane space into matrix • ~4 H+ / ATP • Called chemiosmotic theory

  17. Totals NADH 10 H+ X 1 ATP = 2.5 ATP 4 H+ FADH2 6 H+ X 1 ATP = 1.5 ATP 4 H+

  18. Total ATP from mitochondrial matrix • Pyruvate dehydrogenase • NADH ……………………………….2.5 ATP • Krebs • 3 NADH X 2.5 ATP/NADH ……….7.5 ATP • FADH2 X 1.5 ATP / FADH2……….1.5 ATP • GTP X 1 ATP / GTP ……………..1.0 ATP (from a separate reaction) Total …………….12.5 ATP (Per glucose = X 2 = 25 ATP)

  19. What about NADH from glycolysis? • NADH made in cytosol • Can’t get into matrix of mitochondrion • 2 mechanisms • In muscle and brain • Glycerol phosphate shuttle • In liver and heart • Malate / aspartate shuttle

  20. Glycerol Phosphate shuttle • http://courses.cm.utexas.edu/jrobertus/ch339k/overheads-3/ch19_glycerol-shuttle.jpg

  21. Glycerol phosphate shuttle • In muscle and brain • Each NADH converted to FADH2 inside mitochondrion • FADH2 enters later in the electron transport chain • Produces 1.5 ATP

  22. Total ATP per glucose in muscle and brain • Gycerol phosphate shuttle • 2 NADH per glucose - 2 FADH2 • 2 FADH2 X 1.5 ATP / FADH2……….3.0 ATP • 2 ATP in glycoysis ……………………2.0 ATP • From pyruvate and Krebs • 12.5 ATP X 2 per glucose ……………..25.0 ATP Total = 30.0 ATP/ glucose

  23. Malate – Aspartate Shuttle • http://courses.cm.utexas.edu/emarcotte/ch339k/fall2005/Lecture-Ch19-2/Slide14.JPG

  24. Malate – Aspartate Shuttlein cytosol • In liver and heart • NADH oxidized while reducing oxaloacetate to malate • Malated dehydrogenase • Malate crosses membrane

  25. Malate – Aspartate Shuttlein matrix • Malate reoxidized to oxaloacetate • Malate dehydrogenase • NAD+ reduced to NADH • NADH via electron transport yields 2.5 ATP Mlate – Aspartate Shuttlein cytosol

  26. Total ATP per glucose in liver and heart • Malate – Aspartate Shuttle • 2 NADH per glucose - 2 NADH • 2 NADH X 2.5 ATP / NADH…………5.0 ATP • 2 ATP from glycolysis………………..2.0 ATP • From pyruvate and Krebs • 12.5 ATP X 2 per glucose ……………..25.0 ATP Total = 32.0 ATP/ glucose

  27. Summary • Total ATP / glucose • Muscle and brain 30.0 ATP • Uses glycerol phosphate shuttle • Heart and liver 32.0 ATP • Uses malate aspartate shuttle

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