Chapter 8: Cellular Respiration (Outline)

1. Chapter 8: Cellular Respiration (Outline) • NAD+ and FAD • Phases of Cellular Respiration • Glycolysis • Preparatory (prep) Reaction • Citric Acid Cycle • Electron Transport System (ETC) • Fermentation • Catabolic and Anabolic Reactions

2. Cellular Respiration • A cellular process that requires oxygen and gives off carbon dioxide • Usually involves breakdown of glucose to carbon dioxide and water • Energy extracted from glucose molecule: • Released slowly step-wise • Allows ATP to be produced efficiently • Oxidation-reduction enzymes include NAD+ and FAD as coenzymes

3. Cellular Respiration • Glucose is oxidized and thus releases energy, while oxygen is reducedto form water • The carbon atoms of the sugar molecule are released as carbon dioxide (CO2) • Glucose is high-energy molecule; CO2 and H2O are low-energy molecules thus energy is released

4. Cellular Respiration • Cells carry out cellular respiration in order to build up ATP molecules • Energy is released slowly, step-wise, through many enzymatic reactions in different parts of the cell, why? • Breakdown of glucose realizes a maximum yield of 36 or 38 ATP; this preserves 39% of energy available in glucose

5. NAD+ and FAD • Each metabolic reaction in cellular respiration is catalyzed by its own enzyme • NAD+ is a redox coenzyme that can • Oxidize a metabolite by accepting two electrons and a hydrogen ion; results in NADH • Reduce a metabolite by giving up electrons • FAD is another redox coenzyme • Sometimes used instead of NAD+ • Accepts two electrons and two hydrogen ions (H+) to become FADH2

6. NAD+ and FAD • Electrons received by NAD+ and FAD are high-energy electrons and are usually carried to the electron transport system • Only a small amount of NAD+ is needed in cells, because each NAD+ molecule is used over & over again

7. Phases of Cellular Respiration • Cellular respiration involves four phases • Glycolysis: • Occurs in the cytoplasm • Does not require oxygen; occurs under aerobic or anaerobic conditions • Glucose broken down into two 3-carbon molecules of pyruvate • Enough energy is released for immediate buildup of two ATP molecules

8. Phases of Cellular Respiration • Preparatory (Prep) reaction: • Takes place inside the mitochondrion • Pyruvate is oxidized to a 2-carbon (C2) acetyl group • Electron energy is stored in NADH • CO2 is released as waste product • Occurs twice per glucose molecule

9. Phases of Cellular Respiration • Citric acid cycle: • Series of oxidation reactions occurring in the matrix of mitochondrion (i.e. aerobic) • Electron energy is stored in NADH and FADH2 • Produces two immediate ATP molecules per glucose molecule • Four carbons are released as CO2 • The cycle turns twice per glucose molecule

10. Phases of Cellular Respiration • Electron transport chain: • A series of carriers on the cristae of the mitochondria • Extracts energy from NADH & FADH2 • Electrons pass from higher to lower energy states, energy is released and stored for ATP production, how? • Produces 32 or 34 molecules of ATP per glucose molecule

11. Glucose Breakdown:Overview of the Four Phases

12. Pyruvate • Pyruvate is a pivotal metabolite in cellular respiration • If O2 is not available to the cell, fermentation, an aerobic process, occurs • During fermentation, glucose is incompletely metabolized to lactate or CO2 and alcohol • Fermentation results in a net gain of only two ATP per glucose molecule

13. Glucose Breakdown:Glycolysis • Proceeds in the cytosol • Occurs universally in organisms (i.e. most likely evolved before the citric acid cycle and the electron transport system) • Energy Investment Steps: • The addition of two phosphate groups from ATP to activate glucose in 2 separate reactions • Glucose splits into two (C3) G3P molecules, each with a phosphate group glucose + 2 ATP → 2 G3P + 2 ADP

14. Glycolysis • Energy Harvesting Steps: • In duplicated reactions, NAD+ accepts two electrons and one H+ ion resulting in two NADH • Four ATP molecules are formed by substrate-level ATP synthesis • Net gain of two ATP from glycolysis, why? • Both G3Ps are oxidized to pyruvates • Pyruvate enters mitochondria if oxygen is available and aerobic respiration follows • If oxygen is not available, glycolysis becomes a part of fermentation and pyruvate is reduced

15. Inputs and Outputs of Glycolysis

16. Glycolysis:Substrate-level ATP synthesis • A phosphate group is transferred to ADP giving one ATP molecule • During glycolysis, the C3 substrate BPG gives up a phosphate group to ADP • Occurs twice per glucose molecule

17. Glycolysis

18. Inside the Mitochondria • Aerobic Respiration – involves the preparatory reaction, the citric acid cycle and the electron transport system • Mitochondrion Structure and Function • Double membrane with an intermembrane space between the outer and inner membrane • Cristae - inner folds of membrane • Matrix - the innermost compartment filled with a gel-like fluid • Produces most of the ATP from cellular respiration (i.e. powerhouse of the cell)

19. Mitochondrion:Structure and Function

20. Glucose Breakdown:The Preparatory (Prep) Reaction • Preparatory reaction connects glycolysis to the citric acid cycle • End product of glycolysis (i.e. pyruvate) enters the mitochondrial matrix • Pyruvate is converted to a C2 acetyl group • Attached to CoA to form acetyl CoA • Electrons picked up by 2 NAD+ to give 2 NADH • CO2 is released and transported out of mitochondria into the cytoplasm • Reaction occurs twice per glucose molecule

21. Preparatory Reaction

22. Glucose Breakdown:Citric Acid Cycle • Also known as the Krebs cycle; a cyclic pathway occurring in the matrix of mitochondria • Both (C2) acetyl-CoA groups from the prep reaction: • Joins with a C4 molecule to give citrate (C6) • Each acetyl group is oxidized to two CO2 molecules • Electrons are accepted by NAD+ in three instances (forming 3 NADH) and by FAD in one instance (forming FADH2) • ATP is formed (per acetyl group) by substrate-level ATP synthesis

23. Citric Acid Cycle

24. Inputs and Outputs of The Citric Acid Cycle • Krebs cycle turns twice per glucose molecule

25. Electron Transport Chain (ETC) Location: Eukaryotes – cristae of the mitochondria Aerobic Prokaryotes – plasma membrane Series of carrier molecules: Pass energy rich electrons along Protein carriers such as cytochrome molecules Cytochromes - proteins with a central iron (heme) group; the group is the one being oxidized & reduced Receives electrons from NADH and FADH2

26. ETC (cont.) Oxygen is the final electron acceptor in the ETC Lack of oxygen blocks the entire ETC – no additional ATP is produced leading to death Some poisons also inhibit normal activity of cytochromes Example: Cyanide binds to iron in cytochrome, blocking ATP production

27. Cycling of Carries The fate of the hydrogens: H+ from NADH deliver enough energy to make 3 ATPs Those from FADH2 have only enough for 2 ATPs Recycling of coenzymes increases efficiency Once NADH delivers H+, it returns (as NAD+) to pick up more H+ However, hydrogen atoms must be combined with oxygen to make water If O2 is not present, NADH cannot release H+ No longer recycled back to NAD+

28. ETC

29. Carriers on Cristae of a Mitochondrion The ETC consists of 3 protein complexes and 2 carriers The 3 protein complexes include: NADH-Q reductase complex Cytochrome reductase complex Cytochrome oxidase complex The other 2 carriers are coenzyme Q and cytochrome c H+ carried by NADH and FADH2 are pumped by the protein complexes into the intermembrane space; thus creating H+ gradient

30. Organization and Function of Cristae

31. ATP Production ATP synthase complex –channel protein (in cristae) that serves as an enzyme for ATP synthesis Protons diffuse from the intermembrane space (high conc.) to the matrix (low conc.) through the enzyme complex ATP synthase This catalyzes the phosphorylation of ADP to form ATP – Chemiosmosis ATP molecules them move out of the mitochondria to perform cellular work

32. Mitochondria in Active Tissue ATP production must be constant in order to sustain life Active tissues (e.g. muscles) require greater amounts of ATP and contain more mitochondria than less active cells Example – Dark meat of chickens contains more mitochondria than the white meat of the breast

33. Energy Yield from Glucose Metabolism Complete breakdown of glucose to CO2 and H2O yields 36 to 38 ATPs Substrate-level ATP synthesis 2 ATP from glycolysis 2 AP from the citric acid cycle Total of four ATP are formed outside of the electron transport system 32 to 34 ATP from the electron transport chain and chemiosmosis

34. Energy Yield from Glucose Metabolism (cont.) ETC and Chemiosmosis Per glucose molecule, 10 NADH and two FADH2 provide electrons and H+ ions to electron transport system For each NADH formed within the mitochondrion, 3 ATP are produced For each FADH2 formed by Krebs cycle, 2 ATP result since FADH2 delivers electrons after NADH For each NADH formed in the cytoplasm, 2 ATP are formed as electrons are “shuttled” across the mitochondrial membrane and delivered to FAD

35. Energy Yield from Glucose Breakdown Total NADH = 8 x 3 ATP = 24 ATP Total FADH2 = 2 x 2 ATP = 4 ATP ETC yields 28 ATP 28 (ETC) + 4 (substrate level) = 32 ATP Other 4 ATP comes from NADH produced by glycolysis which transport electrons via shuttle molecule to 2 FADH2, thus 2 x 2ATP = 4 ATP Now we have 32 + 4 = 36 ATP molecules

36. Efficiency of Cellular Respiration Energy difference (∆G) = 686 kcal One ATP phosphate bond has an energy content of 7.3 kcal 36 ATP produced during glucose breakdown (36 x 7.3) = 263 kcal Efficiency is 263/686 x 100 = 39% of available energy from glucose The rest of the energy is lost as heat

37. Overall Energy Yielded per Glucose Molecule

38. Fermentation When oxygen is limited: Spent hydrogens have no final acceptor NADH can’t recycle back to NAD+ Glycolysis stops because NAD+ is required Fermentation: “Anaerobic” pathway Can provide rapid burst of ATP in the absence of O2 Provides NAD+ for glycolysis NADH combines with pyruvate to yield NAD+ NAD+ is then free to return and pick up more e- during earlier reactions of glycolysis

39. Fermentation

40. Fermentation (cont.) • Pyruvate is reduced by NADH to: • Lactate (Animals & anaerobic bacteria) • In muscles, pyruvate is reduced to lactate when it is produced faster than it can be oxidized by Krebs cycle • Cheese & yogurt • Industrial chemicals (i.e. isoprpanol, butyric acid, propionic acid & acetic acid) • Ethanol &carbon dioxide (Yeasts) • Bread & alcoholic beverages

41. Advantages and Disadvantages of Fermentation • Despite the low yield of 2 ATP, it provides a quick burst of energy for muscular activity • Allows glycolysis to proceed faster than O2 can be obtained • Anaerobic exercise • Lactic acid accumulates (toxic to cells) • Causes cramping and oxygen debt • When O2 restored, lactate is broken down to pyruvate; then respired or converted into glucose

42. Efficiency of Fermentation Two ATP produced per glucose molecule during fermentation gives (2 x 7.3)= 14.6 kcal Complete glucose breakdown to CO2 and H2O during cellular respiration = 686 kcal of energy Efficiency is 14.6/686 x 100 = 2.1% Much less efficient than complete breakdown of glucose

43. Catabolic and Anabolic Reactions • Metabolism – sum of all chemical reactions within a living organism • Catabolism – chemical reactions that result in the breakdown of complex organic compounds into simpler substances; thus releases energy • Example: Cellular Respiration • Anabolism – chemical reactions that build new molecules from simpler substances; thus requires energy • Example: Photosynthesis