1. Chapter 9 Cellular Respiration: Harvesting Chemical Energy

2. Figure 9.1 • Overview: Life Is Work • Living cells • Require energy from outside sources to perform their many tasks • Obtain energy for cells by eating food

3. Light energy ECOSYSTEM Photosynthesisin chloroplasts Organicmolecules CO2 + H2O + O2 Cellular respirationin mitochondria ATP powers most cellular work Heatenergy Figure 9.2 • Energy • Flows into an ecosystem as sunlight and leaves as heat

4. Catabolic Pathways and Production of ATP • The breakdown of organic molecules (catabolism) is exergonic • Fermentation • Is a partial degradation of sugars that occurs without oxygen • Cellular respiration • Is the most prevalent and efficient catabolic pathway • Consumes oxygen and organic molecules such as glucose • Yields ATP

5. To keep working cells must regenerate ATP • How? • Catabolic pathways yield energy due to the transfer of electrons.

6. The Principle of Redox • Redox reactions • Transfer electrons from one reactant to another by oxidation and reduction

7. In oxidation • A substance loses electrons, or is oxidized • In reduction • A substance gains electrons, or is reduced • Reducing Agent • The substance that donates electrons • Oxidizing Agent • The substance that accepts electrons

8. becomes oxidized(loses electron) Na + Cl Na+ + Cl– becomes reduced(gains electron) • Na is oxidized and the reducing agent (electron donor) • Cl is reduced and is the oxidizing agent

9. Products Reactants becomes oxidized + + + Energy 2O2 CO2 2 H2O CH4 becomes reduced H C C O O O O H O H H H H Oxygen(oxidizingagent) Methane(reducingagent) Carbon dioxide Water Figure 9.3 • Some redox reactions • Do not completely exchange electrons • Change the degree of electron sharing in covalent bonds

10. becomes oxidized C6H12O6 + 6O2 6CO2 + 6H2O + Energy becomes reduced Oxidation of Organic Fuel Molecules During Cellular Respiration • During cellular respiration • Glucose is oxidized and oxygen is reduced

11. Stepwise Energy Harvest via NAD+ and the Electron Transport Chain • Why are organic compounds excellent sources of energy? • C-H bonds are a source of “hill top” electrons, whose energy may be released as these electrons “fall” down an energy gradient when they are transferred to oxygen

12. 2 e– + 2 H+ 2 e– + H+ NAD+ NADH H Dehydrogenase O O H H Reduction of NAD+ + + 2[H] C NH2 NH2 C (from food) Oxidation of NADH N N+ Nicotinamide(reduced form) Nicotinamide(oxidized form) CH2 O O O O– P O H H OH O O– HO P NH2 HO CH2 O N N H N H N O H H HO OH Figure 9.4 • Electrons from organic compounds • Are usually first transferred to NAD+, a coenzyme H+ H+

13. NADH, the reduced form of NAD+ • Passes the electrons to the electron transport chain

14. H2 + 1/2 O2 Explosiverelease ofheat and lightenergy (a) Uncontrolled reaction Free energy, G Figure 9.5 A H2O • Cellular respiration oxidizes glucose in a series of steps • If electron transfer is not stepwise • A large release of energy occurs • As in the reaction of hydrogen and oxygen to form water

15. The electron transport chain • Passes electrons in a series of steps instead of in one explosive reaction • Uses the energy from the electron transfer to form ATP

16. 2 H + 1/2 O2 (from food via NADH) Controlled release of energy for synthesis ofATP 2 H+ + 2 e– ATP ATP Free energy, G Electron transport chain ATP 2 e– 1/2 O2 2 H+ H2O Figure 9.5 B (b) Cellular respiration

17. The Stages of Cellular Respiration: A Preview • Respiration is a cumulative function of three metabolic stages • Glycolysis • The citric acid cycle • Oxidative phosphorylation

18. Glycolysis • Breaks down glucose into two molecules of pyruvate • The citric acid cycle • Completes the breakdown of glucose • Oxidative phosphorylation • Is driven by the electron transport chain • Generates ATP

19. Electrons carried via NADH and FADH2 Electrons carried via NADH Oxidativephosphorylation:electron transport andchemiosmosis Citric acid cycle Glycolsis Pyruvate Glucose Cytosol Mitochondrion ATP ATP ATP Substrate-level phosphorylation Oxidative phosphorylation Substrate-level phosphorylation Figure 9.6 • An overview of cellular respiration

20. Enzyme Enzyme ADP P Substrate + ATP Product Figure 9.7 • Both glycolysis and the citric acid cycle • Can generate ATP by substrate-level phosphorylation

21. 1. Glycolysis • Glycolysis • Means “splitting of sugar” • Breaks down glucose into pyruvate • Occurs in the cytoplasm of the cell

22. Glycolysis Oxidativephosphorylation Citricacidcycle ATP ATP ATP Energy investment phase Glucose P 2 ATP + 2 used 2 ATP Energy payoff phase formed P 4 ATP 4 ADP + 4 2 NAD+ + 4 e- + 4 H + + 2 H+ 2 NADH 2 Pyruvate + 2 H2O Glucose 2 Pyruvate + 2 H2O 4 ATP formed – 2 ATP used 2 ATP + 2 H+ 2 NADH 2 NAD+ + 4 e– + 4 H + Figure 9.8 • Glycolysis consists of two major phases • Energy investment phase • Energy payoff phase

23. CH2OH Citric acid cycle H H Oxidative phosphorylation H Glycolysis H HO HO OH H OH Glucose 1 2 3 5 4 ATP Hexokinase ADP CH2OH P O H H H H OH HO H OH Glucose-6-phosphate Phosphoglucoisomerase CH2O P O CH2OH H HO HO H H HO Fructose-6-phosphate ATP Phosphofructokinase ADP CH2 O O CH2 P P O HO H OH H HO Fructose- 1, 6-bisphosphate Aldolase H O CH2 P Isomerase C O O C CHOH CH2OH O CH2 P Dihydroxyacetone phosphate Glyceraldehyde- 3-phosphate Figure 9.9 A Energy Investment Phase of Glycolysis

24. 2 NAD+ Triose phosphate dehydrogenase P i 2 2 NADH + 2 H+ 10 7 9 8 6 2 O C O P CHOH P CH2 O 1, 3-Bisphosphoglycerate 2 ADP Phosphoglycerokinase 2 ATP O– 2 C CHOH O P CH2 3-Phosphoglycerate Phosphoglyceromutase O– 2 C O P C H O CH2OH 2-Phosphoglycerate Enolase 2 H2O O– 2 C O P C O CH2 Phosphoenolpyruvate 2 ADP Pyruvate kinase 2 ATP O– 2 C O C O CH3 Figure 9.8 B Pyruvate Energy Payoff Phase of Glycolysis

25. Citric Acid Cycle • The citric acid cycle • Takes place in the matrix of the mitochondrion

26. CYTOSOL MITOCHONDRION + H+ NAD+ NADH O– CoA S 2 C O C O C O CH3 1 3 CH3 Acetyle CoA Pyruvate CO2 Coenzyme A Transport protein Figure 9.10 • Before the citric acid cycle can begin • Pyruvate must first be converted to acetyl CoA, which links the cycle to glycolysis

27. Pyruvate(from glycolysis,2 molecules per glucose) Oxidativephosphorylation Glycolysis Citricacidcycle ATP ATP ATP CO2 CoA NADH + 3 H+ Acetyle CoA CoA CoA Citricacidcycle 2 CO2 3 NAD+ FADH2 FAD 3 NADH + 3 H+ ADP + Pi ATP Figure 9.11 • An overview of the citric acid cycle

28. Citric acid cycle Oxidative phosphorylation Glycolysis S CoA C O CH3 Acetyl CoA CoA SH H2O O C COO– NADH 1 COO– CH2 + H+ COO– CH2 COO– NAD+ Oxaloacetate 8 C COO– HO CH2 2 CH2 HC COO– COO– COO– HO CH HO CH Malate Citrate COO– CH2 Isocitrate COO– CO2 Citric acid cycle 3 H2O 7 NAD+ COO– NADH COO– CH + H+ Fumarate CH2 CoA SH HC a-Ketoglutarate CH2 COO– C O 4 6 SH CoA COO– COO– COO– CH2 5 CH2 FADH2 CO2 CH2 CH2 NAD+ FAD C O COO– Succinate NADH CoA S P i + H+ Succinyl CoA GDP GTP ADP ATP Figure 9.12 Figure 9.12

29. NADH and FADH2 • Donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation • FADH2 – Flavin adenine dinucleotide • In the electron transport chain • Electrons from NADH and FADH2 lose energy in several steps

30. The Totals So Far…

31. At the end of the chain Electrons are passed to oxygen, forming water NADH 50 FADH2 Multiproteincomplexes I 40 FAD FMN II Fe•S Fe•S O III Cyt b 30 Fe•S Cyt c1 IV Free energy (G) relative to O2 (kcl/mol) Cyt c Cyt a Cyt a3 20 10 0 O2 2 H + + 12 Figure 9.13 H2O The Pathway of Electron Transport • At the end of the chain • Electrons are passed to oxygen, forming water Notice: FADH2 enters the chain at a lower energy than NADH.

32. A rotor within the membrane spins clockwise whenH+ flows past it down the H+ gradient. INTERMEMBRANE SPACE H+ H+ H+ H+ H+ H+ H+ A stator anchoredin the membraneholds the knobstationary. A rod (for “stalk”)extending into the knob alsospins, activatingcatalytic sites inthe knob. H+ Three catalytic sites in the stationary knobjoin inorganic Phosphate to ADPto make ATP. ADP + ATP P i MITOCHONDRIAL MATRIX Figure 9.14 Chemiosmosis: The Energy-Coupling Mechanism • ATP synthase • Is the enzyme that actually makes ATP

33. At certain steps along the electron transport chain • Electron transfer causes protein complexes to pump H+ from the mitochondrial matrix to the intermembrane space • Therefore, it is the electron carriers (cytochromes) that set up the H+ electrochemical gradient.

34. The resulting H+ gradient • Stores energy • Drives chemiosmosis in ATP synthase • Is referred to as a proton-motive force

35. Chemiosmosis • Is an energy-coupling mechanism that uses energy in the form of a H+ gradient across a membrane to drive cellular work

36. Inner Mitochondrial membrane Oxidative phosphorylation. electron transport and chemiosmosis Glycolysis ATP ATP ATP H+ H+ H+ H+ Cyt c Protein complex of electron carners Intermembrane space Q IV I III ATP synthase Inner mitochondrial membrane II H2O FADH2 2 H+ + 1/2 O2 FAD+ NADH+ NAD+ ATP ADP + P i (Carrying electrons from, food) H+ Mitochondrial matrix Chemiosmosis ATP synthesis powered by the flow Of H+ back across the membrane Electron transport chain Electron transport and pumping of protons (H+), which create an H+ gradient across the membrane Figure 9.15 Oxidative phosphorylation • Chemiosmosis and the electron transport chain

37. An Accounting of ATP Production by Cellular Respiration • During respiration, most energy flows in this sequence • Glucose to NADH to electron transport chain to proton-motive force to ATP

38. Electron shuttles span membrane MITOCHONDRION CYTOSOL 2 NADH or 2 FADH2 2 FADH2 2 NADH 2 NADH 6 NADH Glycolysis Oxidative phosphorylation: electron transport and chemiosmosis Citric acid cycle 2 Acetyl CoA 2 Pyruvate Glucose + 2 ATP + 2 ATP + about 32 or 34 ATP by oxidative phosphorylation, depending on which shuttle transports electrons from NADH in cytosol by substrate-level phosphorylation by substrate-level phosphorylation About 36 or 38 ATP Maximum per glucose: Figure 9.16 • There are three main processes in this metabolic enterprise

39. About 40% of the energy in a glucose molecule • Is transferred to ATP during cellular respiration, making approximately 38 ATP

40. Cellular respiration • Relies on oxygen to produce ATP • In the absence of oxygen • Cells can still produce ATP through fermentation

41. Glycolysis • Can produce ATP with or without oxygen, in aerobic or anaerobic conditions • Couples with fermentation to produce ATP

42. Types of Fermentation • Fermentation consists of • Glycolysis plus reactions that regenerate NAD+, which can be reused by glyocolysis • In alcohol fermentation • Pyruvate is converted to ethanol in two steps, one of which releases CO2 • During lactic acid fermentation • Pyruvate is reduced directly to NADH to form lactate as a waste product

43. P1 2 ATP 2 ADP + 2 O – C O C O Glucose Glycolysis CH3 2 Pyruvate 2 NADH 2 NAD+ 2 CO2 H H H C O C OH CH3 CH3 2 Ethanol 2 Acetaldehyde (a) Alcohol fermentation P1 2 ATP 2 ADP + 2 Glucose Glycolysis O– C O C O 2 NADH 2 NAD+ CH3 O C O H OH C CH3 2 Lactate (b) Lactic acid fermentation Figure 9.17

44. Glucose CYTOSOL Pyruvate No O2 present Fermentation O2 present Cellular respiration MITOCHONDRION Ethanol or lactate Acetyl CoA Citric acid cycle Figure 9.18 • Pyruvate is a key juncture in catabolism

45. Fermentation and Cellular Respiration Compared • Both fermentation and cellular respiration • Use glycolysis to oxidize glucose and other organic fuels to pyruvate • Fermentation and cellular respiration • Differ in their final electron acceptor • Cellular respiration • Produces more ATP

46. The Evolutionary Significance of Glycolysis • Glycolysis • Occurs in nearly all organisms • Probably evolved in ancient prokaryotes before there was oxygen in the atmosphere

47. The Versatility of Catabolism • Catabolic pathways • Funnel electrons from many kinds of organic molecules into cellular respiration

48. Fats Carbohydrates Proteins Amino acids Fatty acids Sugars Glycerol Glycolysis Glucose Glyceraldehyde-3- P NH3 Pyruvate Acetyl CoA Citric acid cycle Oxidative phosphorylation Figure 9.19 • The catabolism of various molecules from food

49. Regulation of Cellular Respiration via Feedback Mechanisms • Cellular respiration • Is controlled by allosteric enzymes at key points in glycolysis and the citric acid cycle

50. Glucose AMP Glycolysis Stimulates Fructose-6-phosphate + Phosphofructokinase – – Fructose-1,6-bisphosphate Inhibits Inhibits Pyruvate Citrate ATP Acetyl CoA Citric acid cycle Oxidative phosphorylation Figure 9.20 Rate-Limiting Enzyme: PFK • The control of cellular respiration