Mitochondria play a key role in energy production through oxidative phosphorylation. The electron transport chain located in the inner mitochondrial membrane transfers electrons from NADH and FADH2 to oxygen to create a proton gradient. ATP synthase uses this proton gradient to generate ATP from ADP and phosphate. The number of ATP produced depends on whether NADH or FADH2 donate electrons, with NADH producing more ATP. Different tissues use different shuttles like the glycerol phosphate or malate-aspartate shuttle to transport electrons from glycolysis into the mitochondria. Muscle and brain produce 30 ATP per glucose, while heart and liver produce 32 ATP per glucose.

1. Electron Transport and Oxidative Phosphorylation It all reduces down to water. www.freelivedoctor.com

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

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 FADH 2 / glucose www.freelivedoctor.com

4. Electron Transport Chain Groups of redox proteins On inner mitochondrial membrane Binding sites for NADH and FADH 2 On matrix side of membrane Electrons transferred to redox proteins NADH reoxidized to NAD + FADH 2 reoxidized to FAD www.freelivedoctor.com

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 O 2 --  H 2 O www.freelivedoctor.com

6. Electron Transport Chain www.freelivedoctor.com

7. Complex 1 Has NADH binding site NADH reductase activity NADH -  NAD + NADH ---> FMN--->FeS---> ubiquinone ubiquinone ---> ubiquinone H 2 4 H + pumped/NADH www.freelivedoctor.com

8. Electron Transport Chain www.freelivedoctor.com

9. Complex II succinate ---FAD—ubiquinone Contains coenzyme Q FADH 2 binding site FAD reductase activity FADH 2 --  FAD www.freelivedoctor.com

10. Electron Transport Chain www.freelivedoctor.com

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 + / FADH 2 www.freelivedoctor.com

12. Electron Transport Chain www.freelivedoctor.com

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

14. Totals Proton gradient created as electrons transferred to oxygen forming water 10 H + / NADH 6 H + / FADH 2 www.freelivedoctor.com

15. Electron Transport Chain www.freelivedoctor.com

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 www.freelivedoctor.com

17. Totals NADH 10 H + X 1 ATP = 2.5 ATP 4 H + FADH 2 6 H + X 1 ATP = 1.5 ATP 4 H + www.freelivedoctor.com

18. Total ATP from mitochondrial matrix Pyruvate dehydrogenase NADH ……………………………….2.5 ATP Krebs 3 NADH X 2.5 ATP/NADH ……….7.5 ATP FADH 2 X 1.5 ATP / FADH 2 ……….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) www.freelivedoctor.com

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 www.freelivedoctor.com

20. Glycerol Phosphate shuttle www.freelivedoctor.com

21. Glycerol phosphate shuttle In muscle and brain Each NADH converted to FADH 2 inside mitochondrion FADH 2 enters later in the electron transport chain Produces 1.5 ATP www.freelivedoctor.com

22. Total ATP per glucose in muscle and brain Gycerol phosphate shuttle 2 NADH per glucose -  2 FADH 2 2 FADH 2 X 1.5 ATP / FADH 2 ……….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 www.freelivedoctor.com

23. Malate – Aspartate Shuttle www.freelivedoctor.com

24. Malate – Aspartate Shuttle in cytosol In liver and heart NADH oxidized while reducing oxaloacetate to malate Malated dehydrogenase Malate crosses membrane www.freelivedoctor.com

25. Malate – Aspartate Shuttle in matrix Malate reoxidized to oxaloacetate Malate dehydrogenase NAD + reduced to NADH NADH via electron transport yields 2.5 ATP Mlate – Aspartate Shuttle in cytosol www.freelivedoctor.com

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 www.freelivedoctor.com

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 www.freelivedoctor.com