1. 1 Cellular Respiration: Harvesting Chemical Energy

2. 2 Cellular Respiration All cells can harvest energy from organic molecules to power work To do this, they break down the organic molecules and use the energy that is released to make ATP from ADP and phosphate There are different catabolic pathways used in ATP production: Fermentation - the partial degradation of sugars in the absence of oxygen. Cellular respiration - A more efficient and widespread catabolic process that consumes oxygen as a reactant to complete the breakdown of a variety of organic molecules.

3. 3 Catabolic Pathways and Production of ATP Although carbohydrates, fats, and proteins are all consumed as fuel, it is helpful to trace cellular respiration with the sugar glucose: The catabolism of glucose is exergonic with a G of −686 kcal per mole of glucose. Some of this energy is used to produce ATP, which can perform cellular work C6H12O6 + 6O2  6CO2 + 6H2O + Energy (ATP + heat)

4. 4 Redox Reactions Catabolic pathways yield energy through the transfer electrons from one reactant to another by oxidation and reduction Redox reactions In oxidation - A substance loses electrons, or is oxidized In reduction - A substance gains electrons, or is reduced Na + Cl Na + + Cl – becomes oxidized (loses electron) becomes reduced (gains electron)

5. 5 Oxidation of Organic Fuel Molecules During Cellular Respiration Cellular respiration provides the energy for the cell using the exergonic reaction: During cellular respiration glucose is oxidized and oxygen is reduced Glucose oxidation is accomplished in a series of steps C 6 H 12 O 6 + 6O 2 6CO 2 + 6H 2 O + Energy ~686kcal/mole becomes oxidized becomes reduced

6. 6 Glucose Oxidation If electron transfer is not stepwise A large release of energy occurs As in the reaction of hydrogen and oxygen to form water (a) Uncontrolled reaction Free energy, G H2OH2O Explosive release of heat and light energy Figure 9.5 A H 2 + 1 / 2 O 2

7. 7 Glucose catabolism is a series of redox reactions that release energy by repositioning electrons closer to oxygen atoms. The high energy electrons are stripped from glucose and picked up by NAD + and FAD. Glucose Catabolism NAD + H O O OO–O– O O O–O– O O O P P CH 2 HO OH H H HOOH HO H H N+N+ C NH 2 H N H N N Nicotinamide (oxidized form) NH 2 + 2[H] (from food) Dehydrogenase Reduction of NAD + Oxidation of NADH 2 e – + 2 H + 2 e – + H + NADH O H H N C + Nicotinamide (reduced form) N Figure 9.4 H

8. 8 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 Eventually, the electrons, along with H+, are passed to a final acceptor. 2 H 1 / 2 O 2 (from food via NADH ) 2 H + + 2 e – 2 H + 2 e – H2OH2O 1 / 2 O 2 Controlled release of energy for synthesis of ATP ATP Electron transport chain Free energy, G + NADH 50 FADH 2 40 FMN FeS I FAD FeS II III Q FeS Cyt b 30 20 Cyt c Cyt c 1 Cyt a Cyt a 3 IV 10 0 Multiprotein complexes Free energy (G) relative to O2 (kcal/mol) H2OH2O O2O2 2 H + + 1 / 2

9. 9 If molecular oxygen (O 2 ) is the final electron acceptor, the process is called aerobic respiration. If some other inorganic molecule is the final electron acceptor, the process is called anaerobic respiration. If an organic molecule is the final electron acceptor, the process is called fermentation. Glucose Catabolism

10. 10 The Stages of Cellular Respiration Respiration is a cumulative function of three metabolic stages Glycolysis - breaks down glucose into two molecules of pyruvate The Citric Acid Cycle (Kreb’s) - completes the breakdown of glucose Oxidative phosphorylation - driven by the electron transport chain and Generates ATP

11. 11 Cellular Respiration Electrons carried via NADH Glycolsis Glucose Pyruvate ATP Substrate-level phosphorylation Electrons carried via NADH and FADH 2 Citric acid cycle Oxidative phosphorylation: electron transport and chemiosmosis ATP Substrate-level phosphorylation Oxidative phosphorylation Mitochondrion Cytosol

12. 12 Substrate Phosphorylation Both glycolysis and the citric acid cycle can generate ATP by substrate-level phosphorylation Enzyme ATP ADP Product Substrate P + P PEP Enzyme ADP Adenosine P P P ATP P P Adenosine Pyruvate

13. 13 Glycolysis Glycolysis harvests energy by oxidizing glucose to pyruvate Glycolysis Means “splitting of sugar” Breaks down glucose into pyruvate Occurs in the cytoplasm of the cell

14. 14 Glycolysis Occurs in the cytoplasm of the cell Results in the partial breakdown of glucose Anaerobic – no oxygen is used during glycolysis For each molecule of glucose that passes through glycolysis, the cell nets two ATP molecules. Glycolysis Citric acid cycle Oxidative phosphorylation ATP

15. 15 Glycolysis Energy investment phase Glucose ATP ADP Hexokinase ATP Glycolysis Oxidation phosphorylation Citric acid cycle Glucose-6-phosphate ATP/NADH Ledger - 1 ATP

16. 16 Glycolysis Total of 2 ATP invested Glucose ATP ADP Hexokinase ATP Glycolysis Oxidation phosphorylation Citric acid cycle Glucose-6-phosphate Phosphoglucoisomerase Phosphofructokinase Fructose-6-phosphate ATP ADP Fructose- 1, 6-bisphosphate Aldolase Isomerase Dihydroxyacetone phosphate Glyceraldehyde- 3-phosphate ATP/NADH Ledger - 2 ATP

17. 17 Glycolysis Energy payoff phase NAD + Triose phosphate dehydrogenase + H + NADH 1, 3-Bisphosphoglycerate ADP ATP Phosphoglycerokinase Phosphoglyceromutase 2-Phosphoglycerate 3-Phosphoglycerate NAD + Triose phosphate dehydrogenase + H + NADH 1, 3-Bisphosphoglycerate ADP ATP Phosphoglycerokinase Phosphoglyceromutase 2-Phosphoglycerate 3-Phosphoglycerate ATP/NADH Ledger - 2 ATP + 2 ATP + 2 NADH

18. 18 Glycolysis End-products of glycolysis are 2 pyruvate molecules NAD + Triose phosphate dehydrogenase + H + NADH 1, 3-Bisphosphoglycerate ADP ATP Phosphoglycerokinase Phosphoglyceromutase 2-Phosphoglycerate 3-Phosphoglycerate ADP ATP Pyruvate kinase H 2 O Enolase Phosphoenolpyruvate Pyruvate NAD + Triose phosphate dehydrogenase + H + NADH 1, 3-Bisphosphoglycerate ADP ATP Phosphoglycerokinase Phosphoglyceromutase 2-Phosphoglycerate 3-Phosphoglycerate ADP ATP Pyruvate kinase H 2 O Enolase Phosphoenolpyruvate Pyruvate ATP/NADH Ledger - 2 ATP + 4 ATP + 2 NADH

19. 19 Occurs in the cytoplasm Glucose converted to two 3-C chains Anaerobic - no oxygen 2 ATP used, 4 ATP produced Inefficient - net yield only 2 ATPs Not discarded by evolution but used as starting point for energy production If no O 2 - Fermentation occurs End products: 2 ATP Pyruvate (3 C) 2 x CO2 2 x NADH Glycolysis Summary Energy investment phase Glucose 2 ATP used 2 ADP + 2 P 4 ADP + 4 P 4 ATP formed 2 NAD + + 4 e – + 4 H + Energy payoff phase + 2 H + 2 NADH 2 Pyruvate + 2 H 2 O 2 ATP 2 NADH + 2 H + Glucose 4 ATP formed – 2 ATP used 2 NAD+ + 4 e – + 4 H + Net

20. 20 The Citric Acid (Krebs) Cycle The Krebs cycle is named after Hans Krebs and is a metabolic event that follows glycolysis. This process occurs in the fluid matrix of the mitochondrion, uses the pyruvic acid from glycolysis and is aerobic. To begin the Krebs cycle, pyruvic acid is converted to acetyl CoA.

21. 21 Oxidation of Pyruvate More energy can be extracted if oxygen is present Within mitochondria, pyruvate is decarboxylated, yielding acetyl-CoA, NADH, and CO 2 CYTOSOL Pyruvate NAD + MITOCHONDRION Transport protein NADH + H + Coenzyme ACO 2 Acetyl Co A

22. 22 The Citric Acid (Krebs) Cycle Occurs in the mitochondrial matrix Aerobic – although O2 is not used directly in this pathway, it will not occur unless enough is present in the cell. Main catabolic pathway Acetyl-CoA is oxidized in a series of nine reactions

23. 23 AcetylCoA reacts with oxaloacetate using an enzyme called citrate synthase producing citric acid. Because of this, the Krebs cycle is sometimes called the citric acid cycle. ATP Glycolysis Oxidation phosphorylation Citric acid cycle Citric acid cycle Citrate Isocitrate Oxaloacetate Acetyl CoA H2OH2O Krebs Cycle

24. 24 Krebs Cycle The next 7 steps decompose the citrate back to oxaloacetate, Citric acid is systematically decarboxylated and dehyrogenated in order to use up the acetyl groups that were attached to the oxaloacetate. This allows oxaloacetate and CoA to be used in the next cycle. ATP Glycolysis Oxidation phosphorylation Citric acid cycle Citric acid cycle Citrate Isocitrate Oxaloacetate Acetyl CoA H2OH2O CO2CO2 NAD + NADH + H +  -Ketoglutarate CO2CO2 NAD + NADH + H + Succinyl CoA Succinate GTP GDP ADP ATP FAD FADH 2 P i Fumarate

25. 25 Krebs Cycle The NADH and FADH 2 produced by the cycle relay electrons extracted from food to the electron transport chain ATP Glycolysis Oxidation phosphorylation Citric acid cycle Citric acid cycle Citrate Isocitrate Oxaloacetate Acetyl CoA H2OH2O CO2CO2 NAD + NADH + H +  -Ketoglutarate CO2CO2 NAD + NADH + H + Succinyl CoA Succinate GTP GDP ADP ATP FAD FADH 2 P i Fumarate H2OH2O Malate NAD + NADH + H + ATP/NADH Ledger + 2 ATP + 6 NADH + 2 FADH 2

26. 26 Krebs Cycle

27. 27 ETC and Oxidative Phosphorylation Occurs along the inner mitochondrial membrane (IMM) in the cristae of the mitochondrion NADH/FADH2 molecules carry electrons from glycolysis and the citric acid cycle to the inner mitochondrial membrane, where they transfer electrons to a series of membrane-associated proteins.

28. 28 The Pathway of Electron Transport 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 water NADH 50 FADH 2 40 FMN FeS I FAD FeS II III Q FeS Cyt b 30 20 Cyt c Cyt c 1 Cyt a Cyt a 3 IV 10 0 Multiprotein complexes Free energy (G) relative to O2 (kcal/mol) H2OH2O O2O2 2 H + + 1 / 2

29. 29 The Pathway of Electron Transport 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 NADH 50 FADH 2 40 FMN FeS I FAD FeS II III Q FeS Cyt b 30 20 Cyt c Cyt c 1 Cyt a Cyt a 3 IV 10 0 Multiprotein complexes Free energy (G) relative to O2 (kcal/mol) H2OH2O O2O2 2 H + + 1 / 2

30. 30 Electron Transport Phosphorylation Electron transfer in the electron transport chain causes proteins to pump H+ from the mitochondrial matrix to the intermembrane space The ETC uses energy from electrons to pump H+ across a membrane against their concentration gradient - potential energy. 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

31. 31 LE 9-15 Protein complex of electron carriers H+H+ ATP Glycolysis Oxidative phosphorylation: electron transport and chemiosmosis Citric acid cycle H+H+ Q III I II FAD FADH 2 + H + NADH NAD + (carrying electrons from food) Inner mitochondrial membrane Inner mitochondrial membrane Mitochondrial matrix Intermembrane space H+H+ H+H+ Cyt c IV 2H + + 1 / 2 O 2 H2OH2O ADP + H+H+ ATP synthase Electron transport chain Electron transport and pumping of protons (H + ), Which create an H + gradient across the membrane P i Chemiosmosis ATP synthesis powered by the flow of H + back across the membrane Oxidative phosphorylation

32. 32 ATP 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 Most of the ATP produced in cells is made by the enzyme ATP synthase The enzyme is embedded in the membrane and provides a channel through which protons can cross the membrane down their concentration gradient The energy released causes the rotor and the rod structures to rotate. This mechanical energy is converted to chemical energy with the formation of ATP H+H+ ATP ADP + P i Catalytic head Intermembrane space Mitochondrial matrix Rod Rotor H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+

33. 33 LE 9-14 INTERMEMBRANE SPACE H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ ATP MITOCHONDRAL MATRIX ADP + P i A rotor within the membrane spins as shown when H + flows past it down the H + gradient. A stator anchored in the membrane holds the knob stationary. A rod (or “stalk”) extending into the knob also spins, activating catalytic sites in the knob. Three catalytic sites in the stationary knob join inorganic phosphate to ADP to make ATP.

34. 34 Summary of Glucose Catabolism

35. 35 Theoretical ATP Yield of Aerobic Respiration

36. 36 Catabolism of Proteins and Fats Proteins are utilized by deaminating their amino acids, and then metabolizing the product. Fats are utilized by beta-oxidation.

37. 37 Regulating Aerobic Respiration Control of glucose catabolism occurs at two key points in the catabolic pathway. Glycolysis - phosphofructokinase Pyruvate Oxidation – pyruvate decarboxylase

38. 38 Recycling NADH As long as food molecules are available to be converted into glucose, a cell can produce ATP. Continual production creates NADH accumulation and NAD + depletion. NADH must be recycled into NAD +. Aerobic respiration - oxygen as electron acceptor Fermentation - organic molecule

39. 39 Lactic Acid Fermentation Used by most animal cells when O2 is not available NADH donates 2 e- and a H+ directly to the pyruvate (3C) produced during glycolysis, producing lactate (3C) and NAD+ CO O–O– 2 Lactate CHOH Glucose 2 Pyruvate GLYCOLYSISGLYCOLYSIS 2 ATP 2 ADP CO O - CO 2 NAD+ 2 NADH CH 3 CO 2 + 2 H + 2 NADH2 NAD + 2 ATP 2 ADP + 2 P i 2 Pyruvate 2 2 Lactate Lactic acid fermentation Glucose Glycolysis