ETC oxidative phosphorylation BPHARM.pptx

Description of the Electrone transport system with formation of ATP from high energy carrying molecules

1. Electron Transport and Oxidative Phosphorylation BY KAWALYA STEVEN.

2. DESCRIPTION OF ETC WITH DISCUSSION

3. The mitochondrial system is arranged into three complexes of electron carriers . 1, Flavoproteins :  These proteins contain  flavin , a coenzyme derived from riboflavin ( Vit B12). One important flavoprotein is flavin mono nucleotide 2. Ubiquinones (coenzyme Q): These are small non protein carriers. 3. Cytochromes : These are proteins with iron containing group, capable of existing alternately as reduced (Fe2+) and oxidized form (Fe3+). Cytochromes involved in ETC include cyt (b), cyt c1, cyt c, cyt a, cyt a3.

4. The first step, in electron transport chain is the transfer of high energy electrons from NADH to FMN. This transfer actually involves the passage of hydrogen atom with 2 e− to FMN, which then picks up an additional H+ from the surrounding aqueous medium. As a result of the first transfer, NADH is oxidized to NAD+, and FMN is reduced to FMNH2.

5. In the second step, FMNH2  passes 2 H+ to the other side of the mitochondrial membrane and passes 2 e− to coenzyme Q. As a result, FMNH2 is oxidized to FMN. Coenzyme Q also picks up additional 2H+ from the surrounding aqueous and releases to other side of the membrane. In the next step, electrons are passed successively from coenzyme Q to cyt b1, cyt c1, cyt c, cyt a, cyt a3. Each cytochrome in the chain is reduced, as itside of the mitochondrial membrane and passes 2 e− to coenzyme Q. As a result, FMNH2 is oxidized to FMN. Coenzyme Q also picks up additional 2H+ from the surrounding aqueous and releases to other side of the membrane. In the next step, electrons are passed successively from coenzyme Q to cyt b1, cyt c1, cyt c, cyt a, cyt a3. Each cytochrome in the chain is reduced, as it picks up electrons and is oxidized as it gives up electrons. The last cytochrome cyt a3 passes its electrons to molecular O2 which picks up protons from the surrounding medium to form H2O. FADH2 derived from the Krebs cycle is another source of electrons. Thus at the end of ETC, NADH pumps three protons (synthesizes 3ATPs) whereas FADH2 pumps only two protons (synthesizes 2ATPs).

6. Chemiosmotic Mechanism of ATP synthesis . In ETC, when energetic electrons from NADH pass down the carriers, some of the carriers (proton pumps) in the chain pump [actively transport] protons across the membrane to inner membrane space. The mitochondrial matrix becomes polarized. Thus in addition to a concentration gradient, an electrical charge gradient is created. The resulting electro chemical gradient has potential energy called proton motive force.

7. INTRODUCTION IN PPTX 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

8. 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

9. 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

10. 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

11. Electron Transport Chain

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

13. Electron Transport Chain

14. Complex II succinate ---FAD—ubiquinone Contains coenzyme Q FADH 2 binding site FAD reductase activity FADH 2 --  FAD

15. Electron Transport Chain

16. 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

17. Electron Transport Chain

18. 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

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

20. Electron Transport Chain

21. 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 chemi -osmotic theory

22. Totals NADH 10 H + X 1 ATP = 2.5 ATP 4 H + FADH 2 6 H + X 1 ATP = 1.5 ATP 4 H +

23. 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 pyruvate = X 2 = 25 ATP)

24. 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

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

26. 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

27. 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

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

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

30. 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

31. 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

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