Cellular Respiration

1. Cellular Respiration Where did Bruce Lee get all that energy from? Chapter 3

2. What is it? O2 1 36 ATP glucose Cellular resp. • Cellular respiration • An aerobic process (requires oxygen) • Uses chemical energy from glucose to make ATP • Chemical energy is now stored in ATP for use throughout the body

3. Four Main Stages • Glycolysis • Anaerobic • In cytosol • breaks glucose (6C) into 2 pyruvate molecules (3C) • releases ATP • Transition reaction (oxidative decarboxylation) • Pyruvate converted to acetyl CoA releasing CO2 • Kreb’s Cycle • Within mitochondrial matrix • Oxidize each acetyl CoA to CO2 • Releases ATP and co-enzymes (NADH, FADH2) • Electron Transport Chain • Along the inner mitochondrial membrane • Uses high energy electrons from NADH and FADH2 to create an electrochemical proton (H+) gradient which powers ATP synthesis

4. Fermentation • When oxygen is NOT available, cells can metabolize pyruvate by the process of fermentation. Two Types (i) alcohol fermentation: pyruvate (3C) converted (reduced) to ethyl alcohol (2C) and CO2; occurs in yeast cells (ii) lactic acid fermentation: pyruvate(3C) converted (reduced) to lactic acid (3C) in muscle cells

5. Glycolysis (I) 1.Activation: Phosphate from ATP is added to glucose to form glucose-6-phosphate. [substrate-level phosphorylation] 2. Isomerization: Glucose-6-phosphate is rearranged to form fructose-6-phosphate. 3. Activation: A second phosphate from another ATP is added to form fructose-1,6-diphosphate. [substrate-level phosphorylation] 4. Cleavage: The unstable fructose-1,6-diphosphate splits into phosphoglyceraldehyde (PGAL) and dihydroxyacetone phosphate (DHAP). 5. Isomerization: The DHAP molecule is converted to PGAL. Investment

6. Glycolysis (II) 6.Activation/Redox: Each molecule of PGAL is oxidized by NAD and gains a phosphate to form 1,3-bisphosphoglycerate (PGAP). 7. Phosphorylation: Each PGAP loses a phosphate to ADP resulting in 2 ATP and two 3-phosphoglycerate molecules (3-PGA).[substrate-level phosphorylation] 8. Isomerization: Both 3-PGA molecules are rearranged to form 2-phosphoglycerate (2-PGA). [note: the text does not distinguish between 3-PGA and 2-PGA, but refers to both as PGA] 9. Dehydration: Both 2-PGA molecules are oxidized to phosphoenol pyruvate (PEP) by the removal of water. 10.Phosphorylation: Each PEP molecule loses a phosphate to ADP resulting in 2 more ATP and 2 molecules of pyruvate. [substrate-level phosphorylation] Pay-off

7. The Result 1 3 6 2 ATP 7 2 NADH 10 (high energy molecule) In Glycolysis • Used 2 ATP • Made 4 ATP Net Gain: 4 – 2 = And

8. Glycolysis: overall reaction O2 C6H12O6 + 2ADP + 2P + 2NAD  2C3H4O3 + 2NADH + 2ATP glucose (6C) pyruvate (3C) Notice: There is no oxygen used in glycolysis. It is an anaerobic process

9. The Power House! nucleus mitochondria • In the cytosol, for each glucose molecule consumed, only 2 ATP were produced • This means that 34 more ATP are made in the mitochondria! • How do we get in there and what happens inside!? cytosol ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP

10. Inside the Mitochondria

11. Inside the Mitochondria • outer membrane: contains transport protein porin, which affects permeability • inner membrane: contains the phospholipid cardiolipin that makes membrane impermeable to ions, a condition which is required for ATP production • intermembrane space: fluid-filled area containing enzymes and hydrogen ions • matrix: location of Kreb’s Cycle • cristae: folds of the inner membrane where ETC enzymes are found

12. Transition Reaction C – C – C pyruvate mitochondrion cytosol • multi-enzyme pyruvate dehydrogenase complex

13. Transition Reaction C – C – C CO2 pyruvate mitochondrion cytosol 1. Decarboxylation C – C

14. Transition Reaction mitochondrion cytosol NAD NADH 2. Oxidation C – C C – C

15. Transition Reaction mitochondrion cytosol C – C 3. Attachment CoA

16. Transition Reaction C – C CoA mitochondrion cytosol Acetyl CoA 3. Attachment

17. Transition Reaction • Decarboxylation (-CO2) of pyruvate leaving a 2C molecule • Oxidation by NAD+ forming an acetate molecule. • Attachment of coenzyme A forming acetyl coA. Steps A and B together are referred to as oxidative decarboxylation

18. Transition Reaction 1 is released CO2 1 NADH is prodcued • In the transition reaction, for each molecule of pyruvate: and

19. Transition Reaction 1 2 is released are released CO2 CO2 1 2 and NADH NADH is produced and are prodcued • Remember: There are 2 pyruvates produced for each glucose. Therefore, for each glucose: X2

20. Krebs Cycle 1. Acetyl coA breaks into coenzyme A, which is recycled, and an acetyl group (2C) which joins to oxaloacetate (4C) forming citrate (6C). 2. Citrate (6C) converts to isocitrate (6C). 3. Isocitrate (6C) loses CO2 and is then oxidized by NAD forming alpha-ketoglutarate (5C). [oxidative decarboxylation] 4. Alpha-ketoglutarate (5C) is converted to succinyl-coA (4C) in 3 steps: (i) loss of CO2 (ii) oxidation by NAD+ (iii) attachment of coenzyme A

21. Krebs Cycle 5. Succinyl coA (4C) is converted to succinate (4C) in the following way: - coenzyme A breaks off and is recycled; phosphate attaches temporarily to succinate and is then transferred to GDP forming GTP; GTP transfers phosphate to ADP forming ATP (substrate level phosphorylation). 6. Succinate (4C) is oxidized by FAD to form fumarate (4C). 7. Water is added to fumarate (4C) to form malate (4C). 8. Malate (4C) is oxidized by NAD+ to form oxaloacetate, which is regenerated to begin the cycle again.

22. Krebs Cycle Transition reaction Krebs Cycle

23. Krebs Cycle 2 are released CO2 3 NADH 1 ATP 1 FADH2 • In the Krebs Cycle for each molecule of pyruvate: and are produced

24. Krebs Cycle 2 4 are released are released CO2 CO2 6 3 and NADH NADH 1 ATP and 1 FADH2 2 ATP 2 FADH2 are prodcued are produced • Remember: There are 2 pyruvates produced for each glucose. Therefore, for each glucose: X2

25. The Story So Far 1 glucose 2 6 C – C – C CO2 pyruvate Tracking carbon: (6C) (1C) (3C)

26. The Story So Far 4 2 2 ATP ATP ATP in cytosol 2 2 6 2 2 NADH NADH NADH FADH2 FADH2 10 NADH Tracking High Energy Molecules

27. Using the High Energy Molecules • NADH and FADH2 have high energy electrons • These electrons are donated to electron carrier proteins in the ETC • The energy from these electrons is then used to pump protons (H+) into the intermembrane space of the mitchondria

28. Electron Transport Chain Electron Carriers: • 1. NADH reductase [protein] • 2. Coenzyme Q [non-protein] • 3. Cytochromeb1 c1 • 4. Cytochrome c • 5. Cytochromec oxidase C Cristae Q Cytochrome b1c1 Cytochrome c Cytochrome c oxidase NADH reductase Co-enzyme Q ATP Synthase [protein; contain iron]

29. Electron Transport Chain • as electrons flow along ETC, each carrier is reduced (gains electrons) then oxidized (donates electrons) • electrons come from hydrogen atoms (H atoms separate into electrons and protons) C Cristae Q

30. Electron Transport Chain • NADH donates a pair of electrons to NADH reductase • electrons continue along ETC C Cristae Q NAD+ NADH

31. Electron Transport Chain • FADH2 donates a pair of electrons to coenzyme Q • electrons also continue along ETC C Cristae Q FADH2

32. Electron Transport Chain • FADH2 donates a pair of electrons to coenzyme Q • electrons also continue along ETC C Cristae Q

33. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ For each NADH, 6 H+ are pumped across the mitochondrion inner membrane C Cristae Q NAD+ H+ H+ H+ H+ H+ H+ H+ NADH H+ H+ H+ H+ H+ H+

34. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ O2 H+ H+ H2O H+ H+ For each NADH, 6 H+ are pumped across the mitochondrion inner membrane Oxygen is the final electron acceptor and is converted to H2O C Cristae Q H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

35. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ O2 H+ H+ H2O H+ H+ For each FADH2, 4 H+ are pumped across the mitochondrion inner membrane C Cristae Q H+ H+ H+ H+ H+ H+ FADH2 H+ H+ H+ H+

36. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ High Proton Concentration H+ H+ Gradient The proton gradient C Cristae Q H+ Low Proton Concentration H+ H+ H+ H+ H+

37. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ • Using the energy stored in the proton gradient, ATP is generated using oxidative phosphorylation: formation of ATP coupled to oxygen consumption C Cristae Q ATP H+ H+ H+ H+ H+ H+ Using the electrochemial proton gradient is called chemiosmosis

38. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ 6 Pumps H+ H+ H+ H+ H+ H+ H+ H+ 1 ATP is generated for each proton pair flowing through ATP synthase. C Cristae Q ATP ATP ATP H+ H+ H+ H+ H+ H+ 3 NADH

39. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ 4 Pumps H+ H+ H+ H+ H+ H+ H+ H+ 1 ATP is generated for each proton pair flowing through ATP synthase. C Cristae Q ATP ATP H+ H+ H+ H+ H+ H+ 2 FADH2

40. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ The WHOLE process… C Cristae Q H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

41. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ The WHOLE process… C Cristae Q NAD+ H+ H+ H+ H+ H+ H+ H+ NADH H+ H+ H+ H+ H+ H+

42. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ O2 H+ H+ H2O H+ H+ C Cristae Q H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ The WHOLE process…

43. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ C Cristae Q ATP ATP ATP H+ H+ H+ H+ H+ H+ The WHOLE process…

44. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ C Cristae Q H+ H+ H+ H+ H+ H+ The WHOLE process… ATP ATP ATP

45. Summing up ATP 4 2 2 ATP ATP ATP in cytosol 2 2 6 2 2 NADH NADH NADH FADH2 FADH2 10 NADH Remember: BEFORE the ETC we had…

46. Summing up ATP 6 4 ATP ATP 2 6 2 22 2 2 ATP NADH NADH NADH FADH2 FADH2 32 ATP In the Electron Transport Chain in cytosol 10 NADH

47. Summing up ATP 6 4 2 + From Glycolysis ATP ATP ATP 6 2 2 22 2 2 ATP NADH NADH NADH FADH2 FADH2 32 34 2 ATP ATP ATP IN TOTAL in cytosol 10 NADH

48. Summing up ATP 6 4 2 + From Krebs Cycle ATP ATP ATP 2 6 2 22 2 2 ATP NADH NADH NADH FADH2 FADH2 34 36 2 2 ATP ATP ATP ATP IN TOTAL in cytosol 10 NADH