1. Chapter 9 Cellular Respiration: Harvesting Chemical Energy

2. Overview: Life Is Work Living cells require energy from outside sources Some animals, such as the giant panda, obtain energy by eating plants, and some animals feed on other organisms that eat plants Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

3. Fig. 9-1

4. Energy flows into an ecosystem as sunlight and leaves as heat Photosynthesis generates O 2 and organic molecules, which are used in cellular respiration Cells use chemical energy stored in organic molecules to regenerate ATP, which powers work Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

5. Fig. 9-2 Light energy ECOSYSTEM Photosynthesis in chloroplasts CO 2 + H 2 O Cellular respiration in mitochondria Organic molecules + O 2 ATP powers most cellular work Heat energy ATP

6. Concept 9.1: Catabolic pathways yield energy by oxidizing organic fuels Several processes are central to cellular respiration and related pathways Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

7. Catabolic Pathways and Production of ATP The breakdown of organic molecules is exergonic Fermentation is a partial degradation of sugars that occurs without O 2 Aerobic respiration consumes organic molecules and O 2 and yields ATP Anaerobic respiration is similar to aerobic respiration but consumes compounds other than O 2 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

8. Cellular respiration includes both aerobic and anaerobic respiration but is often used to refer to aerobic respiration Although carbohydrates, fats, and proteins are all consumed as fuel, it is helpful to trace cellular respiration with the sugar glucose: C 6 H 12 O 6 + 6 O 2  6 CO 2 + 6 H 2 O + Energy (ATP + heat) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

9. Redox Reactions: Oxidation and Reduction The transfer of electrons during chemical reactions releases energy stored in organic molecules This released energy is ultimately used to synthesize ATP Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

10. The Principle of Redox Chemical reactions that transfer electrons between reactants are called oxidation-reduction reactions, or redox reactions In oxidation, a substance loses electrons, or is oxidized In reduction, a substance gains electrons, or is reduced (the amount of positive charge is reduced) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

11. Fig. 9-UN1 becomes oxidized (loses electron) becomes reduced (gains electron)

12. Fig. 9-UN2 becomes oxidized becomes reduced

13. The electron donor is called the reducing agent The electron receptor is called the oxidizing agent Some redox reactions do not transfer electrons but change the electron sharing in covalent bonds An example is the reaction between methane and O 2 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

14. Fig. 9-UN4 Dehydrogenase

15. Fig. 9-4 Dehydrogenase Reduction of NAD + Oxidation of NADH 2 e – + 2 H + 2 e – + H + NAD + + 2[H] NADH + H+H+ H+H+ Nicotinamide (oxidized form) Nicotinamide (reduced form)

16. The Stages of Cellular Respiration: A Preview Cellular respiration has three stages: – Glycolysis (breaks down glucose into two molecules of pyruvate) – The citric acid cycle (completes the breakdown of glucose) – Oxidative phosphorylation (accounts for most of the ATP synthesis) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

17. Cellular Respiration C 6 H 12 O 6 + 6O 2 + 36ADP + 36P i  6CO 2 + 6H 2 O + 36ATP

18. Basic Steps Involved Glycolysis Krebs Cycle Electron Transport System Acetyl CoA Formation 1 2 3 4

19. Overview of Glycolysis

20. Other Metabolic Pathways Fats Glycogen Protein

22. Fig. 9-6-1 Substrate-level phosphorylation ATP Cytosol Glucose Pyruvate Glycolysis Electrons carried via NADH

23. Fig. 9-6-2 Mitochondrion Substrate-level phosphorylation ATP Cytosol Glucose Pyruvate Glycolysis Electrons carried via NADH Substrate-level phosphorylation ATP Electrons carried via NADH and FADH 2 Citric acid cycle

24. Fig. 9-6-3 Mitochondrion Substrate-level phosphorylation ATP Cytosol Glucose Pyruvate Glycolysis Electrons carried via NADH Substrate-level phosphorylation ATP Electrons carried via NADH and FADH 2 Oxidative phosphorylation ATP Citric acid cycle Oxidative phosphorylation: electron transport and chemiosmosis

25. Fig. 9-8 Energy investment phase Glucose 2 ADP + 2 P 2 ATPused formed 4 ATP Energy payoff phase 4 ADP + 4 P 2 NAD + + 4 e – + 4 H + 2 NADH + 2 H + 2 Pyruvate + 2 H 2 O Glucose Net 4 ATP formed – 2 ATP used2 ATP 2 NAD + + 4 e – + 4 H + 2 NADH + 2 H +

26. Fig. 9-9-1 ATP ADP Hexokinase 1 ATP ADP Hexokinase 1 Glucose Glucose-6-phosphate Glucose Glucose-6-phosphate

27. Fig. 9-9-2 Hexokinase ATP ADP 1 Phosphoglucoisomerase 2 Phosphogluco- isomerase 2 Glucose Glucose-6-phosphate Fructose-6-phosphate Glucose-6-phosphate Fructose-6-phosphate

28. 1 Fig. 9-9-3 Hexokinase ATP ADP Phosphoglucoisomerase Phosphofructokinase ATP ADP 2 3 ATP ADP Phosphofructo- kinase Fructose- 1, 6-bisphosphate Glucose Glucose-6-phosphate Fructose-6-phosphate Fructose- 1, 6-bisphosphate 1 2 3 Fructose-6-phosphate 3

29. Fig. 9-9-4 Glucose ATP ADP Hexokinase Glucose-6-phosphate Phosphoglucoisomerase Fructose-6-phosphate ATP ADP Phosphofructokinase Fructose- 1, 6-bisphosphate Aldolase Isomerase Dihydroxyacetone phosphate Glyceraldehyde- 3-phosphate 1 2 3 4 5 Aldolase Isomerase Fructose- 1, 6-bisphosphate Dihydroxyacetone phosphate Glyceraldehyde- 3-phosphate 4 5

30. Fig. 9-9-5 2 NAD + NADH 2 + 2 H + 2 2P i Triose phosphate dehydrogenase 1, 3-Bisphosphoglycerate 6 2 NAD + Glyceraldehyde- 3-phosphate Triose phosphate dehydrogenase NADH2 + 2 H + 2 P i 1, 3-Bisphosphoglycerate 6 2 2

31. Fig. 9-9-6 2 NAD + NADH 2 Triose phosphate dehydrogenase + 2 H + 2 P i 2 2 ADP 1, 3-Bisphosphoglycerate Phosphoglycerokinase 2 ATP 2 3-Phosphoglycerate 6 7 2 2 ADP 2 ATP 1, 3-Bisphosphoglycerate 3-Phosphoglycerate Phosphoglycero- kinase 2 7

32. Fig. 9-9-7 3-Phosphoglycerate Triose phosphate dehydrogenase 2 NAD + 2 NADH + 2 H + 2 P i 2 2 ADP Phosphoglycerokinase 1, 3-Bisphosphoglycerate 2 ATP 3-Phosphoglycerate 2 Phosphoglyceromutase 2-Phosphoglycerate 2 2 2 Phosphoglycero- mutase 6 7 8 8

33. Fig. 9-9-8 2 NAD + NADH2 2 2 2 2 + 2 H + Triose phosphate dehydrogenase 2 P i 1, 3-Bisphosphoglycerate Phosphoglycerokinase 2 ADP 2 ATP 3-Phosphoglycerate Phosphoglyceromutase Enolase 2-Phosphoglycerate 2 H 2 O Phosphoenolpyruvate 9 8 7 6 2 2-Phosphoglycerate Enolase 2 2 H 2 O Phosphoenolpyruvate 9

34. Fig. 9-9-9 Triose phosphate dehydrogenase 2 NAD + NADH 2 2 2 2 2 2 2 ADP 2 ATP Pyruvate Pyruvate kinase Phosphoenolpyruvate Enolase 2 H 2 O 2-Phosphoglycerate Phosphoglyceromutase 3-Phosphoglycerate Phosphoglycerokinase 2 ATP 2 ADP 1, 3-Bisphosphoglycerate + 2 H + 6 7 8 9 10 2 2 ADP 2 ATP Phosphoenolpyruvate Pyruvate kinase 2 Pyruvate 10 2 P i

35. Fig. 9-10 CYTOSOLMITOCHONDRION NAD + NADH+ H + 2 1 3 Pyruvate Transport protein CO 2 Coenzyme A Acetyl CoA

36. The citric acid cycle, also called the Krebs cycle, takes place within the mitochondrial matrix The cycle oxidizes organic fuel derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH 2 per turn Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

37. Fig. 9-11 Pyruvate NAD + NADH + H + Acetyl CoA CO 2 CoA Citric acid cycle FADH 2 FAD CO 2 2 3 3 NAD + + 3 H + ADP +P i ATP NADH

38. The citric acid cycle has eight steps, each catalyzed by a specific enzyme The acetyl group of acetyl CoA joins the cycle by combining with oxaloacetate, forming citrate The next seven steps decompose the citrate back to oxaloacetate, making the process a cycle The NADH and FADH 2 produced by the cycle relay electrons extracted from food to the electron transport chain Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

39. Krebs Cycle (Citric Acid Cycle)

40. Fig. 9-12-1 Acetyl CoA Oxaloacetate CoA—SH 1 Citrate Citric acid cycle

41. Fig. 9-12-2 Acetyl CoA Oxaloacetate Citrate CoA—SH Citric acid cycle 1 2 H2OH2O Isocitrate

42. Fig. 9-12-3 Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Citric acid cycle Isocitrate 1 2 3 NAD + NADH + H +  -Keto- glutarate CO2CO2

43. Fig. 9-12-4 Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + Citric acid cycle  -Keto- glutarate CoA—SH 1 2 3 4 NAD + NADH + H + Succinyl CoA CO2CO2 CO2CO2

44. Fig. 9-12-5 Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2 Citric acid cycle CoA—SH  -Keto- glutarate CO2CO2 NAD + NADH + H + Succinyl CoA 1 2 3 4 5 CoA—SH GTP GDP ADP P i Succinate ATP

45. Fig. 9-12-6 Acetyl CoA CoA—SH Oxaloacetate H2OH2O Citrate Isocitrate NAD + NADH + H + CO2CO2 Citric acid cycle CoA—SH  -Keto- glutarate CO2CO2 NAD + NADH + H + CoA—SH P Succinyl CoA i GTP GDP ADP ATP Succinate FAD FADH 2 Fumarate 1 2 3 4 5 6

46. Fig. 9-12-7 Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2  -Keto- glutarate CoA—SH NAD + NADH Succinyl CoA CoA—SH PP GDP GTP ADP ATP Succinate FAD FADH 2 Fumarate Citric acid cycle H2OH2O Malate 1 2 5 6 7 i CO2CO2 + H + 3 4

47. Fig. 9-12-8 Acetyl CoA CoA—SH Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2  -Keto- glutarate CoA—SH CO2CO2 NAD + NADH + H + Succinyl CoA CoA—SH P i GTP GDP ADP ATP Succinate FAD FADH 2 Fumarate Citric acid cycle H2OH2O Malate Oxaloacetate NADH +H + NAD + 1 2 3 4 5 6 7 8

48. Balance Sheet for the Transition Reaction and Krebs Cycle Input 2 Pyruvate 2 ADP + 2 P i 8 NAD + 2 FAD Output 6 CO 2 2 ATP 8 NADH 2 FADH 2

49. Oxidative Phosphorylation Chemiosmosis Electrons are transferred from complex to complex and some of their energy is used to pump protons (H + ) into the intermembrane space, creating a proton gradient. ATP synthesis is powered by the flow of H + back across the inner mitochondrial membrane through ATP synthase.

50. Each Glucose Molecule CO 2 6 NADH10 FADH 2 2 ATP4

51. Concept 9.3: The citric acid cycle completes the energy-yielding oxidation of organic molecules In the presence of O 2, pyruvate enters the mitochondrion Before the citric acid cycle can begin, pyruvate must be converted to acetyl CoA, which links the cycle to glycolysis Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

52. The Pathway of Electron Transport The electron transport chain is in the cristae of the mitochondrion Most of the chain’s components are proteins, which exist in multiprotein complexes The carriers alternate reduced and oxidized states as they accept and donate electrons Electrons drop in free energy as they go down the chain and are finally passed to O 2, forming H 2 O Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

53. Fig. 9-13 NADH NAD + 2 FADH 2 2 FAD Multiprotein complexes FAD FeS FMN FeS Q  Cyt b   Cyt c 1 Cyt c Cyt a Cyt a 3 IVIV Free energy (G) relative to O 2 (kcal/mol) 50 40 30 20 10 2 (from NADH or FADH 2 ) 0 2 H + + 1 / 2 O2O2 H2OH2O e–e– e–e– e–e–

54. Electrons are transferred from NADH or FADH 2 to the electron transport chain Electrons are passed through a number of proteins including cytochromes (each with an iron atom) to O 2 The electron transport chain generates no ATP The chain’s function is to break the large free- energy drop from food to O 2 into smaller steps that release energy in manageable amounts Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

55. Chemiosmosis: The Energy-Coupling Mechanism Electron transfer in the electron transport chain causes proteins to pump H + from the mitochondrial matrix to the intermembrane space H + then moves back across the membrane, passing through channels in ATP synthase ATP synthase uses the exergonic flow of H + to drive phosphorylation of ATP This is an example of chemiosmosis, the use of energy in a H + gradient to drive cellular work Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

56. Electron Transport System CO 2 6 NADH10 FADH 2 2 ATP4 used to make ATP

57. Electron Transport System 4

59. +Pi

60. Electron Transport Chain and Oxidative Phosphorylation Electrons are delivered to O, forming O – O – attracts H + to form H 2 O

61. Figure 24.9 Glycolysis Krebs cycle Electron trans- port chain and oxidative phosphorylation Enzyme Complex I Enzyme Complex III Enzyme Complex IV Enzyme Complex II NADH+H + FADH 2 Free energy relative to O 2 (kcal/mol)

62. Electronic Energy Gradient Transfer of energy from NADH + H + and FADH 2 to oxygen releases large amounts of energy This energy is released in a stepwise manner through the electron transport chain

63. ATP Synthase Two major parts connected by a rod 1.Rotor in the inner mitochondrial membrane 2.Knob in the matrix Works like an ion pump in reverse

64. Fig. 9-UN7 INTER- MEMBRANE SPACE H+H+ ATP synthase ATPADP + P i H+H+ MITO- CHONDRIAL MATRIX

65. Figure 24.11 Mitochondrial matrix Intermembrane space ADP + A stator anchored in the membrane holds the knob stationary. As the rotor spins, a rod connecting the cylindrical rotor and knob also spins. The protruding, stationary knob contains three catalytic sites that join inorganic phosphate to ADP to make ATP when the rod is spinning. A rotor in the membrane spins clockwise when H + flows through it down the H + gradient.

66. Net ATP Yield 34 to 36 molecules ATP for every glucose molecule about 40% efficiency ATP

67. Transition cycle

68. Overall ATP Production Electron Transport System34 Citric Acid Cycle2 Glycolysis2 SUBTOTAL38 NADH Transport into Mitochondrion* -2 TOTAL36

69. The energy stored in a H + gradient across a membrane couples the redox reactions of the electron transport chain to ATP synthesis The H + gradient is referred to as a proton- motive force, emphasizing its capacity to do work

70. Fig. 9-16 Protein complex of electron carriers H+H+ H+H+ H+H+ Cyt c Q    VV FADH 2 FAD NAD + NADH (carrying electrons from food) Electron transport chain 2 H + + 1 / 2 O 2 H2OH2O ADP + P i Chemiosmosis Oxidative phosphorylation H+H+ H+H+ ATP synthase ATP 21

71. An Accounting of ATP Production by Cellular Respiration During cellular respiration, most energy flows in this sequence: glucose  NADH  electron transport chain  proton-motive force  ATP About 40% of the energy in a glucose molecule is transferred to ATP during cellular respiration, making about 38 ATP

72. Fig. 9-17 Maximum per glucose: About 36 or 38 ATP + 2 ATP + about 32 or 34 ATP Oxidative phosphorylation: electron transport and chemiosmosis Citric acid cycle 2 Acetyl CoA Glycolysis Glucose 2 Pyruvate 2 NADH 6 NADH2 FADH 2 2 NADH CYTOSOL Electron shuttles span membrane or MITOCHONDRION

73. Fermentation (Anaerobic Respiration)

74. Fig. 9-18a 2 ADP + 2 P i 2 ATP GlucoseGlycolysis 2 Pyruvate 2 NADH2 NAD + + 2 H + CO 2 2 Acetaldehyde 2 Ethanol (a) Alcohol fermentation 2

75. Fig. 9-18b Glucose 2 ADP + 2 P i 2 ATP Glycolysis 2 NAD + 2 NADH + 2 H + 2 Pyruvate 2 Lactate (b) Lactic acid fermentation

76. Fermentation and Aerobic Respiration Compared Both processes use glycolysis to oxidize glucose and other organic fuels to pyruvate The processes have different final electron acceptors: an organic molecule (such as pyruvate or acetaldehyde) in fermentation and O 2 in cellular respiration Cellular respiration produces 38 ATP per glucose molecule; fermentation produces 2 ATP per glucose molecule

77. Obligate anaerobes carry out fermentation or anaerobic respiration and cannot survive in the presence of O 2 Yeast and many bacteria are facultative anaerobes, meaning that they can survive using either fermentation or cellular respiration In a facultative anaerobe, pyruvate is a fork in the metabolic road that leads to two alternative catabolic routes

78. Fig. 9-19 Glucose Glycolysis Pyruvate CYTOSOL No O 2 present: Fermentation O 2 present: Aerobic cellular respiration MITOCHONDRION Acetyl CoA Ethanol or lactate Citric acid cycle

79. The Evolutionary Significance of Glycolysis Glycolysis occurs in nearly all organisms Glycolysis probably evolved in ancient prokaryotes before there was oxygen in the atmosphere

80. Concept 9.6: Glycolysis and the citric acid cycle connect to many other metabolic pathways Gycolysis and the citric acid cycle are major intersections to various catabolic and anabolic pathways

81. The Versatility of Catabolism Catabolic pathways funnel electrons from many kinds of organic molecules into cellular respiration Glycolysis accepts a wide range of carbohydrates Proteins must be digested to amino acids; amino groups can feed glycolysis or the citric acid cycle

82. Fats are digested to glycerol (used in glycolysis) and fatty acids (used in generating acetyl CoA) Fatty acids are broken down by beta oxidation and yield acetyl CoA An oxidized gram of fat produces more than twice as much ATP as an oxidized gram of carbohydrate

83. Fig. 9-20 Proteins Carbohydrates Amino acids Sugars Fats GlycerolFatty acids Glycolysis Glucose Glyceraldehyde-3- Pyruvate P NH 3 Acetyl CoA Citric acid cycle Oxidative phosphorylation

84. Biosynthesis (Anabolic Pathways) The body uses small molecules to build other substances These small molecules may come directly from food, from glycolysis, or from the citric acid cycle

85. Regulation of Cellular Respiration via Feedback Mechanisms Feedback inhibition is the most common mechanism for control If ATP concentration begins to drop, respiration speeds up; when there is plenty of ATP, respiration slows down Control of catabolism is based mainly on regulating the activity of enzymes at strategic points in the catabolic pathway

86. You should now be able to: 1.Explain in general terms how redox reactions are involved in energy exchanges 2.Name the three stages of cellular respiration; for each, state the region of the eukaryotic cell where it occurs and the products that result 3.In general terms, explain the role of the electron transport chain in cellular respiration

87. 4.Explain where and how the respiratory electron transport chain creates a proton gradient 5.Distinguish between fermentation and anaerobic respiration 6.Distinguish between obligate and facultative anaerobes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

88. INQUIRY 1.What is the end product in glycolysis? 2.What substance is produced by the oxidation of pyruvate and feeds into the citric acid cycle? 3.Name a product of fermentation. 4.What role does O 2 play in aerobic respiration? 5.What stage during cellular respiration is the most ATP synthesized? 6.What is chemiosmosis? 7.When NAD + and FAD + are reduced what do they form? 8.What are they used for?