Cellular Respiration and Fermentation 7 Cellular Respiration and Fermentation

Overview: Life Is Work Living cells require energy from outside sources Some animals, such as the giraffe, obtain energy by eating plants, and some animals feed on other organisms that eat plants © 2014 Pearson Education, Inc. 2

Figure 7.1 Figure 7.1 How do these leaves power the work of life for this giraffe? 3

Energy flows into an ecosystem as sunlight and leaves as heat Photosynthesis generates O2 and organic molecules, which are used as fuel for cellular respiration Cells use chemical energy stored in organic molecules to regenerate ATP, which powers work Animation: Carbon Cycle © 2014 Pearson Education, Inc. 4

Light energy ECOSYSTEM Photosynthesis in chloroplasts Organic Figure 7.2 Light energy ECOSYSTEM Photosynthesis in chloroplasts Organic molecules CO2  H2O  O2 Cellular respiration in mitochondria Figure 7.2 Energy flow and chemical recycling in ecosystems ATP powers most cellular work ATP Heat energy 5

Concept 7.1: Catabolic pathways yield energy by oxidizing organic fuels Several processes are central to cellular respiration and related pathways © 2014 Pearson Education, Inc. 6

Catabolic Pathways and Production of ATP The breakdown of organic molecules is exergonic Fermentation is a partial degradation of sugars that occurs without O2 Aerobic respiration consumes organic molecules and O2 and yields ATP Anaerobic respiration is similar to aerobic respiration but consumes compounds other than O2 © 2014 Pearson Education, Inc. 7

C6H12O6  6 O2  6 CO2  6 H2O  Energy (ATP  heat) 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 C6H12O6  6 O2  6 CO2  6 H2O  Energy (ATP  heat) © 2014 Pearson Education, Inc. 8

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 © 2014 Pearson Education, Inc. 9

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) © 2014 Pearson Education, Inc. 10

becomes oxidized (loses electron) becomes reduced (gains electron) Figure 7.UN01 becomes oxidized (loses electron) becomes reduced (gains electron) Figure 7.UN01 In-text figure, NaCl redox reaction, p. 136 11

becomes oxidized becomes reduced Figure 7.UN02 becomes oxidized becomes reduced Figure 7.UN02 In-text figure, generalized redox reaction, p. 136 12

The electron donor is called the reducing agent The electron acceptor 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 O2 © 2014 Pearson Education, Inc. 13

Reactants Products becomes oxidized becomes reduced Methane (reducing Figure 7.3 Reactants Products becomes oxidized becomes reduced Figure 7.3 Methane combustion as an energy-yielding redox reaction Methane (reducing agent) Oxygen (oxidizing agent) Carbon dioxide Water 14

Redox reactions that move electrons closer to electronegative atoms, like oxygen, release chemical energy that can be put to work © 2014 Pearson Education, Inc. 15

Oxidation of Organic Fuel Molecules During Cellular Respiration During cellular respiration, the fuel (such as glucose) is oxidized, and O2 is reduced Organic molecules with an abundance of hydrogen, like carbohydrates and fats, are excellent fuels As hydrogen (with its electron) is transferred to oxygen, energy is released that can be used in ATP sythesis © 2014 Pearson Education, Inc. 16

becomes oxidized becomes reduced Figure 7.UN03 becomes oxidized becomes reduced Figure 7.UN03 In-text figure, cellular respiration redox reaction, p. 137 17

Stepwise Energy Harvest via NAD+ and the Electron Transport Chain In cellular respiration, glucose and other organic molecules are broken down in a series of steps Electrons from organic compounds are usually first transferred to NAD, a coenzyme As an electron acceptor, NAD functions as an oxidizing agent during cellular respiration Each NADH (the reduced form of NAD) represents stored energy that is tapped to synthesize ATP © 2014 Pearson Education, Inc. 18

2 e− 2 H 2 e−  H NAD NADH H Dehydrogenase Reduction of NAD Figure 7.4 2 e− 2 H 2 e−  H NAD NADH H Dehydrogenase Reduction of NAD  2[H] (from food)  H Oxidation of NADH Nicotinamide (reduced form) Nicotinamide (oxidized form) Figure 7.4 NAD+ as an electron shuttle 19

NAD Nicotinamide (oxidized form) Figure 7.4a Figure 7.4a NAD+ as an electron shuttle (part 1: NAD+ structure) 20

2 e−  2 H 2 e−  H H NADH Dehydrogenase Reduction of NAD   2[H] Figure 7.4b 2 e−  2 H 2 e−  H H NADH Dehydrogenase Reduction of NAD  2[H] (from food)  H Oxidation of NADH Nicotinamide (reduced form) Figure 7.4b NAD+ as an electron shuttle (part 2: NAD+ reaction) 21

Figure 7.UN04 Figure 7.UN04 In-text figure, dehydrogenase reaction, p. 138 22

NADH passes the electrons to the electron transport chain Unlike an uncontrolled reaction, the electron transport chain passes electrons in a series of steps instead of one explosive reaction O2 pulls electrons down the chain in an energy-yielding tumble The energy yielded is used to regenerate ATP © 2014 Pearson Education, Inc. 23

(a) Uncontrolled reaction (b) Cellular respiration Figure 7.5 ½ ½ H2  O2 2 H  O2 Controlled release of energy 2 H  2 e− ATP ATP Explosive release Electron transport chain Free energy, G Free energy, G ATP 2 e− Figure 7.5 An introduction to electron transport chains ½ O2 2 H H2O H2O (a) Uncontrolled reaction (b) Cellular respiration 24

The Stages of Cellular Respiration: A Preview Harvesting of energy from glucose has three stages Glycolysis (breaks down glucose into two molecules of pyruvate) Pyruvate oxidation and the citric acid cycle (completes the breakdown of glucose) Oxidative phosphorylation (accounts for most of the ATP synthesis) Animation: Cellular Respiration © 2014 Pearson Education, Inc. 25

Glycolysis (color-coded teal throughout the chapter) Figure 7.UN05 1. Glycolysis (color-coded teal throughout the chapter) 2. Pyruvate oxidation and the citric acid cycle (color-coded salmon) 3. Oxidative phosphorylation: electron transport and chemiosmosis (color-coded violet) Figure 7.UN05 In-text figure, color code for stages of cellular respiration, p. 139 26

Electrons via NADH Glycolysis Glucose Pyruvate CYTOSOL MITOCHONDRION Figure 7.6-1 Electrons via NADH Glycolysis Glucose Pyruvate CYTOSOL MITOCHONDRION Figure 7.6-1 An overview of cellular respiration (step 1) ATP Substrate-level 27

Electrons via NADH and FADH2 Electrons via NADH Pyruvate oxidation Figure 7.6-2 Electrons via NADH and FADH2 Electrons via NADH Pyruvate oxidation Glycolysis Citric acid cycle Glucose Pyruvate Acetyl CoA CYTOSOL MITOCHONDRION Figure 7.6-2 An overview of cellular respiration (step 2) ATP ATP Substrate-level Substrate-level 28

Electrons via NADH and FADH2 Electrons via NADH Oxidative Figure 7.6-3 Electrons via NADH and FADH2 Electrons via NADH Oxidative phosphorylation: electron transport and chemiosmosis Pyruvate oxidation Glycolysis Citric acid cycle Glucose Pyruvate Acetyl CoA CYTOSOL MITOCHONDRION Figure 7.6-3 An overview of cellular respiration (step 3) ATP ATP ATP Substrate-level Substrate-level Oxidative 29

The process that generates most of the ATP is called oxidative phosphorylation because it is powered by redox reactions © 2014 Pearson Education, Inc. 30

Oxidative phosphorylation accounts for almost 90% of the ATP generated by cellular respiration A smaller amount of ATP is formed in glycolysis and the citric acid cycle by substrate-level phosphorylation For each molecule of glucose degraded to CO2 and water by respiration, the cell makes up to 32 molecules of ATP © 2014 Pearson Education, Inc. 31

Enzyme Enzyme ADP Substrate  ATP Product Figure 7.7 Enzyme Enzyme ADP P Substrate  ATP Figure 7.7 Substrate-level phosphorylation Product 32

Concept 7.2: Glycolysis harvests chemical energy by oxidizing glucose to pyruvate Glycolysis (“sugar splitting”) breaks down glucose into two molecules of pyruvate Glycolysis occurs in the cytoplasm and has two major phases Energy investment phase Energy payoff phase Glycolysis occurs whether or not O2 is present © 2014 Pearson Education, Inc. 33

Citric acid cycle Oxidative phosphorylation Pyruvate oxidation Figure 7.UN06 Citric acid cycle Oxidative phosphorylation Pyruvate oxidation Glycolysis Figure 7.UN06 In-text figure, mini-map, glycolysis, p. 140 ATP ATP ATP 34

Energy Investment Phase Figure 7.8 Energy Investment Phase Glucose 2 ADP  2 P 2 ATP used Energy Payoff Phase 4 ADP  4 P 4 ATP formed 2 NAD  4 e−  4 H 2 NADH  2 H Figure 7.8 The energy input and output of glycolysis 2 Pyruvate  2 H2O Net Glucose 2 Pyruvate  2 H2O 4 ATP formed − 2 ATP used 2 ATP 2 NAD  4 e−  4 H 2 NADH  2 H 35

Glycolysis: Energy Investment Phase Figure 7.9a Glycolysis: Energy Investment Phase Glyceraldehyde 3-phosphate (G3P) ATP Glucose 6-phosphate Fructose 6-phosphate ATP Fructose 1,6-bisphosphate Glucose ADP ADP Isomerase 5 Hexokinase Phosphogluco- isomerase Phospho- fructokinase Aldolase Dihydroxyacetone phosphate (DHAP) 1 4 2 3 Figure 7.9a A closer look at glycolysis (part 1: investment phase) 36

Glycolysis: Energy Investment Phase Figure 7.9aa-1 Glycolysis: Energy Investment Phase Glucose Figure 7.9aa-1 A closer look at glycolysis (part 1a, step 1) 37

Glycolysis: Energy Investment Phase Figure 7.9aa-2 Glycolysis: Energy Investment Phase ATP Glucose 6-phosphate Glucose ADP Hexokinase 1 Figure 7.9aa-2 A closer look at glycolysis (part 1a, step 2) 38

Glycolysis: Energy Investment Phase Figure 7.9aa-3 Glycolysis: Energy Investment Phase ATP Glucose 6-phosphate Fructose 6-phosphate Glucose ADP Hexokinase Phosphogluco- isomerase 1 Figure 7.9aa-3 A closer look at glycolysis (part 1a, step 3) 2 39

Glycolysis: Energy Investment Phase Figure 7.9ab-1 Glycolysis: Energy Investment Phase Fructose 6-phosphate Figure 7.9ab-1 A closer look at glycolysis (part 1b, step 1) 40

Glycolysis: Energy Investment Phase Figure 7.9ab-2 Glycolysis: Energy Investment Phase Fructose 6-phosphate Fructose 1,6-bisphosphate ATP ADP Phospho- fructokinase Figure 7.9ab-2 A closer look at glycolysis (part 1b, step 2) 3 41

Glycolysis: Energy Investment Phase Figure 7.9ab-3 Glycolysis: Energy Investment Phase Glyceraldehyde 3-phosphate (G3P) Fructose 6-phosphate Fructose 1,6-bisphosphate ATP ADP Isomerase 5 Phospho- fructokinase Aldolase Dihydroxyacetone phosphate (DHAP) 4 Figure 7.9ab-3 A closer look at glycolysis (part 1b, step 3) 3 42

Glycolysis: Energy Payoff Phase Figure 7.9b Glycolysis: Energy Payoff Phase 2 ATP 2 ATP 2 NADH 2 H2O Glyceraldehyde 3-phosphate (G3P) 2 ADP 2 NAD  2 H 2 ADP 2 2 2 2 2 Triose phosphate dehydrogenase Phospho- glycerokinase Phospho- glyceromutase Enolase Pyruvate kinase 2 P i 9 1,3-Bisphospho- glycerate 7 3-Phospho- glycerate 8 2-Phospho- glycerate Phosphoenol- pyruvate (PEP) 10 Pyruvate 6 Figure 7.9b A closer look at glycolysis (part 2: payoff phase) 43

Glycolysis: Energy Payoff Phase Figure 7.9ba-1 Glycolysis: Energy Payoff Phase Glyceraldehyde 3-phosphate (G3P) Isomerase 5 Aldolase Dihydroxyacetone phosphate (DHAP) 4 Figure 7.9ba-1 A closer look at glycolysis (part 2a, step 1) 44

Glycolysis: Energy Payoff Phase Figure 7.9ba-2 Glycolysis: Energy Payoff Phase 2 NADH Glyceraldehyde 3-phosphate (G3P) 2 NAD  2 H 2 Triose phosphate dehydrogenase 2 P i Isomerase 1,3-Bisphospho- glycerate 5 6 Aldolase Dihydroxyacetone phosphate (DHAP) 4 Figure 7.9ba-2 A closer look at glycolysis (part 2a, step 2) 45

Glycolysis: Energy Payoff Phase Figure 7.9ba-3 Glycolysis: Energy Payoff Phase 2 ATP 2 NADH Glyceraldehyde 3-phosphate (G3P) 2 NAD  2 H 2 ADP 2 2 Triose phosphate dehydrogenase Phospho- glycerokinase 2 P i Isomerase 1,3-Bisphospho- glycerate 7 3-Phospho- glycerate 5 6 Aldolase Dihydroxyacetone phosphate (DHAP) 4 Figure 7.9ba-3 A closer look at glycolysis (part 2a, step 3) 46

Glycolysis: Energy Payoff Phase Figure 7.9bb-1 Glycolysis: Energy Payoff Phase 2 3-Phospho- glycerate Figure 7.9bb-1 A closer look at glycolysis (part 2b, step 1) 47

Glycolysis: Energy Payoff Phase Figure 7.9bb-2 Glycolysis: Energy Payoff Phase 2 H2O 2 2 2 Phospho- glyceromutase Enolase 9 3-Phospho- glycerate 8 2-Phospho- glycerate Phosphoenol- pyruvate (PEP) Figure 7.9bb-2 A closer look at glycolysis (part 2b, step 2) 48

Glycolysis: Energy Payoff Phase Figure 7.9bb-3 Glycolysis: Energy Payoff Phase 2 ATP 2 H2O 2 ADP 2 2 2 2 Phospho- glyceromutase Enolase Pyruvate kinase 9 3-Phospho- glycerate 8 2-Phospho- glycerate Phosphoenol- pyruvate (PEP) 10 Pyruvate Figure 7.9bb-3 A closer look at glycolysis (part 2b, step 3) 49

Concept 7.3: After pyruvate is oxidized, the citric acid cycle completes the energy-yielding oxidation of organic molecules In the presence of O2, pyruvate enters the mitochondrion (in eukaryotic cells), where the oxidation of glucose is completed Before the citric acid cycle can begin, pyruvate must be converted to acetyl coenzyme A (acetyl CoA), which links glycolysis to the citric acid cycle © 2014 Pearson Education, Inc. 50

Citric acid cycle Oxidative phosphorylation Pyruvate oxidation Figure 7.UN07 Citric acid cycle Oxidative phosphorylation Pyruvate oxidation Glycolysis Figure 7.UN07 In-text figure, mini-map, pyruvate oxidation, p. 142 ATP ATP ATP 51

Citric acid cycle Figure 7.10 Pyruvate (from glycolysis, 2 molecules per glucose) CYTOSOL CO2 NAD CoA NADH  H Acetyl CoA MITOCHONDRION CoA CoA Citric acid cycle Figure 7.10 An overview of pyruvate oxidation and the citric acid cycle 2 CO2 FADH2 3 NAD FAD 3 NADH  3 H ADP  P i ATP 52

2 molecules per glucose) CYTOSOL Figure 7.10a Pyruvate (from glycolysis, 2 molecules per glucose) CYTOSOL CO2 NAD CoA Figure 7.10a An overview of pyruvate oxidation and the citric acid cycle (part 1: pyruvate oxidation) NADH  H Acetyl CoA MITOCHONDRION CoA 53

Citric acid cycle Acetyl CoA CoA CoA 2 CO2 FADH2 3 NAD 3 NADH FAD Figure 7.10b Acetyl CoA CoA CoA Citric acid cycle 2 CO2 FADH2 3 NAD Figure 7.10b An overview of pyruvate oxidation and the citric acid cycle (part 2: citric acid cycle) 3 NADH FAD  3 H ADP  P i ATP 54

The citric acid cycle, also called the Krebs cycle, completes the breakdown of pyruvate to CO2 The cycle oxidizes organic fuel derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH2 per turn © 2014 Pearson Education, Inc. 55

Citric acid cycle Oxidative phosphorylation Pyruvate oxidation Figure 7.UN08 Citric acid cycle Oxidative phosphorylation Pyruvate oxidation Glycolysis Figure 7.UN08 In-text figure, mini-map, citric acid cycle, p. 143 ATP ATP ATP 56

Citric acid cycle Figure 7.11-1 Acetyl CoA 1 Oxaloacetate 2 Citrate CoA-SH 1 H2O Oxaloacetate 2 Citrate Isocitrate Citric acid cycle Figure 7.11-1 A closer look at the citric acid cycle (steps 1-2) 57

Citric acid cycle Figure 7.11-2 Acetyl CoA 1 Oxaloacetate 2 Citrate CoA-SH 1 H2O Oxaloacetate 2 Citrate Isocitrate NAD Citric acid cycle 3 NADH  H CO2 -Ketoglutarate Figure 7.11-2 A closer look at the citric acid cycle (step 3) 58

Citric acid cycle Figure 7.11-3 Acetyl CoA 1 Oxaloacetate 2 Citrate CoA-SH 1 H2O Oxaloacetate 2 Citrate Isocitrate NAD Citric acid cycle 3 NADH  H CO2 CoA-SH -Ketoglutarate Figure 7.11-3 A closer look at the citric acid cycle (step 4) 4 CO2 NAD NADH Succinyl CoA  H 59

Citric acid cycle Figure 7.11-4 Acetyl CoA 1 Oxaloacetate 2 Citrate CoA-SH 1 H2O Oxaloacetate 2 Citrate Isocitrate NAD Citric acid cycle 3 NADH  H CO2 CoA-SH -Ketoglutarate Figure 7.11-4 A closer look at the citric acid cycle (step 5) 4 CoA-SH 5 CO2 NAD Succinate P NADH i GTP GDP Succinyl CoA  H ADP ATP formation ATP 60

Citric acid cycle Figure 7.11-5 Acetyl CoA 1 Oxaloacetate 2 Malate CoA-SH 1 H2O Oxaloacetate 2 Malate Citrate Isocitrate NAD Citric acid cycle 3 NADH 7  H H2O CO2 Fumarate CoA-SH -Ketoglutarate Figure 7.11-5 A closer look at the citric acid cycle (steps 6-7) 6 4 CoA-SH 5 FADH2 CO2 NAD FAD Succinate P NADH i GTP GDP Succinyl CoA  H ADP ATP formation ATP 61

Citric acid cycle Figure 7.11-6 Acetyl CoA 1 Oxaloacetate 8 2 Malate CoA-SH NADH 1  H H2O NAD Oxaloacetate 8 2 Malate Citrate Isocitrate NAD Citric acid cycle 3 NADH 7  H H2O CO2 Fumarate CoA-SH -Ketoglutarate Figure 7.11-6 A closer look at the citric acid cycle (step 8) 6 4 CoA-SH 5 FADH2 CO2 NAD FAD Succinate P NADH i GTP GDP Succinyl CoA  H ADP ATP formation ATP 62

Start: Acetyl CoA adds its two-carbon group to oxaloacetate, producing Figure 7.11a Start: Acetyl CoA adds its two-carbon group to oxaloacetate, producing citrate; this is a highly exergonic reaction. Acetyl CoA CoA-SH 1 H2O Oxaloacetate Figure 7.11a A closer look at the citric acid cycle (part 1) 2 Citrate Isocitrate 63

Isocitrate is oxidized; NAD is reduced. Figure 7.11b Isocitrate Redox reaction: Isocitrate is oxidized; NAD is reduced. NAD NADH 3  H CO2 CO2 release CoA-SH -Ketoglutarate 4 Figure 7.11b A closer look at the citric acid cycle (part 2) CO2 release CO2 NAD Redox reaction: After CO2 release, the resulting four-carbon molecule is oxidized (reducing NAD), then made reactive by addition of CoA. NADH Succinyl CoA  H 64

Succinate is oxidized; FAD is reduced. Figure 7.11c Fumarate 6 CoA-SH 5 FADH2 FAD Redox reaction: Succinate is oxidized; FAD is reduced. Succinate P i GTP GDP Succinyl CoA Figure 7.11c A closer look at the citric acid cycle (part 3) ADP ATP formation ATP 65

Redox reaction: Malate is oxidized; NAD is reduced. Oxaloacetate 8 Figure 7.11d Redox reaction: Malate is oxidized; NAD is reduced. NADH  H NAD 8 Oxaloacetate Malate 7 Figure 7.11d A closer look at the citric acid cycle (part 4) H2O Fumarate 66

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 FADH2 produced by the cycle relay electrons extracted from food to the electron transport chain © 2014 Pearson Education, Inc. 67

Concept 7.4: During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis Following glycolysis and the citric acid cycle, NADH and FADH2 account for most of the energy extracted from food These two electron carriers donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation © 2014 Pearson Education, Inc. 68

The Pathway of Electron Transport The electron transport chain is in the inner membrane (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 O2, forming H2O © 2014 Pearson Education, Inc. 69

Oxidative phosphorylation: electron transport and chemiosmosis Citric Figure 7.UN09 Oxidative phosphorylation: electron transport and chemiosmosis Citric acid cycle Pyruvate oxidation Glycolysis Figure 7.UN09 In-text figure, mini-map, oxidative phosphorylation, p. 144 ATP ATP ATP 70

Free energy (G) relative to O2 (kcal/mol) Figure 7.12 NADH 50 2 e− NAD FADH2 Multiprotein complexes 2 e− FAD 40 I FMN II Fe•S Fe•S Q III Cyt b 30 Fe•S Cyt c1 IV Free energy (G) relative to O2 (kcal/mol) Cyt c Cyt a Cyt a3 20 Figure 7.12 Free-energy change during electron transport 10 2 e− (originally from NADH or FADH2) 2 H  ½ O2 H2O 71

Free energy (G) relative to O2 (kcal/mol) Figure 7.12a NADH 50 2 e− NAD FADH2 2 e− FAD Multiprotein complexes I 40 FMN II Fe•S Fe•S Q III Cyt b Free energy (G) relative to O2 (kcal/mol) Fe•S 30 Cyt c1 IV Cyt c Figure 7.12a Free-energy change during electron transport (part 1) Cyt a Cyt a3 20 2 e− 10 72

Free energy (G) relative to O2 (kcal/mol) Figure 7.12b 30 Cyt c1 IV Cyt c Cyt a Cyt a3 20 Free energy (G) relative to O2 (kcal/mol) 2 e− 10 (originally from NADH or FADH2) Figure 7.12b Free-energy change during electron transport (part 2) 2 H  ½ O2 H2O 73

The electron transport chain generates no ATP directly Electrons are transferred from NADH or FADH2 to the electron transport chain Electrons are passed through a number of proteins including cytochromes (each with an iron atom) to O2 The electron transport chain generates no ATP directly It breaks the large free-energy drop from food to O2 into smaller steps that release energy in manageable amounts © 2014 Pearson Education, Inc. 74

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 the protein complex, 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 © 2014 Pearson Education, Inc. 75

Video: ATP Synthase 3-D Side View Video: ATP Synthase 3-D Top View © 2014 Pearson Education, Inc. 76

H INTERMEMBRANE SPACE Stator Rotor Internal rod Catalytic knob ADP  Figure 7.13 H INTERMEMBRANE SPACE Stator Rotor Internal rod Catalytic knob Figure 7.13 ATP synthase, a molecular mill ADP  P ATP MITOCHONDRIAL MATRIX i 77

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 © 2014 Pearson Education, Inc. 78

Oxidative phosphorylation: electron transport and chemiosmosis Citric Figure 7.UN09 Oxidative phosphorylation: electron transport and chemiosmosis Citric acid cycle Pyruvate oxidation Glycolysis Figure 7.UN09 In-text figure, mini-map, oxidative phosphorylation, p. 146 ATP ATP ATP 79

Electron transport chain Oxidative phosphorylation Figure 7.14 H H Protein complex of electron carriers H H Cyt c IV Q III I ATP synthase II 2 H  ½ O2 H2O FADH2 FAD NADH NAD Figure 7.14 Chemiosmosis couples the electron transport chain to ATP synthesis ADP  P ATP i (carrying electrons from food) H 1 Electron transport chain 2 Chemiosmosis Oxidative phosphorylation 80

Electron transport chain Figure 7.14a H H Protein complex of electron carriers H Cyt c IV Q III I II 2 H  ½ O2 H2O FADH2 FAD Figure 7.14a Chemiosmosis couples the electron transport chain to ATP synthesis (part 1: electron transport chain) NAD NADH (carrying electrons from food) 1 Electron transport chain 81

2 ATP synthase Chemiosmosis H H ADP  ATP i P Figure 7.14b Figure 7.14b Chemiosmosis couples the electron transport chain to ATP synthesis (part 2: chemiosmosis) ADP  P ATP i H 2 Chemiosmosis 82

An Accounting of ATP Production by Cellular Respiration During cellular respiration, most energy flows in the following sequence: glucose  NADH  electron transport chain  proton-motive force  ATP About 34% of the energy in a glucose molecule is transferred to ATP during cellular respiration, making about 32 ATP There are several reasons why the number of ATP molecules is not known exactly © 2014 Pearson Education, Inc. 83

Electron shuttles span membrane MITOCHONDRION 2 NADH CYTOSOL or Figure 7.15 Electron shuttles span membrane MITOCHONDRION 2 NADH CYTOSOL or 2 FADH2 2 NADH 2 NADH 6 NADH 2 FADH2 Glycolysis Pyruvate oxidation 2 Acetyl CoA Oxidative phosphorylation: electron transport and chemiosmosis Citric acid cycle 2 Pyruvate Glucose  2 ATP Figure 7.15 ATP yield per molecule of glucose at each stage of cellular respiration  2 ATP  about 26 or 28 ATP About 30 or 32 ATP Maximum per glucose: 84

Electron shuttles span membrane 2 NADH or 2 FADH2 2 NADH Glycolysis 2 Figure 7.15a Electron shuttles span membrane 2 NADH or 2 FADH2 2 NADH Glycolysis 2 Pyruvate Glucose Figure 7.15a ATP yield per molecule of glucose at each stage of cellular respiration (part 1: glycolysis)  2 ATP 85

Pyruvate oxidation 2 Acetyl CoA Citric acid cycle Figure 7.15b 2 NADH 6 NADH 2 FADH2 Pyruvate oxidation 2 Acetyl CoA Citric acid cycle Figure 7.15b ATP yield per molecule of glucose at each stage of cellular respiration (part 2: citric acid cycle)  2 ATP 86

2 NADH or 2 FADH2 2 NADH 6 NADH 2 FADH2 Oxidative phosphorylation: Figure 7.15c 2 NADH or 2 FADH2 2 NADH 6 NADH 2 FADH2 Oxidative phosphorylation: electron transport and chemiosmosis Figure 7.15c ATP yield per molecule of glucose at each stage of cellular respiration (part 3: oxidative phosphorylation)  about 26 or 28 ATP 87

About Maximum per glucose: 30 or 32 ATP Figure 7.15d Figure 7.15d ATP yield per molecule of glucose at each stage of cellular respiration (part 4: yield per glucose) 88

Concept 7.5: Fermentation and anaerobic respiration enable cells to produce ATP without the use of oxygen Most cellular respiration requires O2 to produce ATP Without O2, the electron transport chain will cease to operate In that case, glycolysis couples with fermentation or anaerobic respiration to produce ATP © 2014 Pearson Education, Inc. 89

Anaerobic respiration uses an electron transport chain with a final electron acceptor other than O2, for example, sulfate Fermentation uses substrate-level phosphorylation instead of an electron transport chain to generate ATP © 2014 Pearson Education, Inc. 90

Types of Fermentation Fermentation consists of glycolysis plus reactions that regenerate NAD, which can be reused by glycolysis Two common types are alcohol fermentation and lactic acid fermentation © 2014 Pearson Education, Inc. 91

In alcohol fermentation, pyruvate is converted to ethanol in two steps The first step releases CO2 from pyruvate, and the second step reduces acetaldehyde to ethanol Alcohol fermentation by yeast is used in brewing, winemaking, and baking Animation: Fermentation Overview © 2014 Pearson Education, Inc. 92

(a) Alcohol fermentation (b) Lactic acid fermentation Figure 7.16 2 ADP  2 P 2 ADP  2 i 2 ATP P i 2 ATP Glucose Glycolysis Glucose Glycolysis 2 Pyruvate 2 NAD 2 NADH 2 CO2 2 NAD 2 NADH  2 H  2 H 2 Pyruvate Figure 7.16 Fermentation 2 Ethanol 2 Acetaldehyde 2 Lactate (a) Alcohol fermentation (b) Lactic acid fermentation 93

(a) Alcohol fermentation Figure 7.16a 2 ADP  2 P 2 ATP i Glucose Glycolysis 2 Pyruvate 2 NAD 2 NADH 2 CO2  2 H Figure 7.16a Fermentation (part 1: alcohol) 2 Acetaldehyde 2 Ethanol (a) Alcohol fermentation 94

(b) Lactic acid fermentation Figure 7.16b 2 ADP  2 P 2 ATP i Glucose Glycolysis 2 NAD 2 NADH  2 H 2 Pyruvate Figure 7.16b Fermentation (part 2: lactic acid) 2 Lactate (b) Lactic acid fermentation 95

In lactic acid fermentation, pyruvate is reduced by NADH, forming lactate as an end product, with no release of CO2 Lactic acid fermentation by some fungi and bacteria is used to make cheese and yogurt Human muscle cells use lactic acid fermentation to generate ATP when O2 is scarce © 2014 Pearson Education, Inc. 96

Comparing Fermentation with Anaerobic and Aerobic Respiration All use glycolysis (net ATP  2) to oxidize glucose and harvest chemical energy of food In all three, NAD is the oxidizing agent that accepts electrons during glycolysis The processes have different final electron acceptors: an organic molecule (such as pyruvate or acetaldehyde) in fermentation and O2 in cellular respiration Cellular respiration produces 32 ATP per glucose molecule; fermentation produces 2 ATP per glucose molecule © 2014 Pearson Education, Inc. 97

Obligate anaerobes carry out only fermentation or anaerobic respiration and cannot survive in the presence of O2 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 © 2014 Pearson Education, Inc. 98

Ethanol, lactate, or other products Citric acid cycle Figure 7.17 Glucose Glycolysis CYTOSOL Pyruvate No O2 present: Fermentation O2 present: Aerobic cellular respiration MITOCHONDRION Ethanol, lactate, or other products Acetyl CoA Figure 7.17 Pyruvate as a key juncture in catabolism Citric acid cycle 99

The Evolutionary Significance of Glycolysis Ancient prokaryotes are thought to have used glycolysis long before there was oxygen in the atmosphere Very little O2 was available in the atmosphere until about 2.7 billion years ago, so early prokaryotes likely used only glycolysis to generate ATP Glycolysis is a very ancient process © 2014 Pearson Education, Inc. 100

Concept 7.6: 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 © 2014 Pearson Education, Inc. 101

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 and amino groups must be removed before amino acids can feed glycolysis or the citric acid cycle © 2014 Pearson Education, Inc. 102

Fats are digested to glycerol (used in glycolysis) and fatty acids 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 © 2014 Pearson Education, Inc. 103

Amino acids Fatty acids Figure 7.18-1 Proteins Carbohydrates Fats Amino acids Sugars Glycerol Fatty acids Figure 7.18-1 The catabolism of various molecules from food (step 1) 104

Amino acids Fatty acids Figure 7.18-2 Proteins Carbohydrates Fats Amino acids Sugars Glycerol Fatty acids Glycolysis Glucose Glyceraldehyde 3- P NH3 Pyruvate Figure 7.18-2 The catabolism of various molecules from food (step 2) 105

Amino acids Fatty acids Figure 7.18-3 Proteins Carbohydrates Fats Amino acids Sugars Glycerol Fatty acids Glycolysis Glucose Glyceraldehyde 3- P NH3 Pyruvate Figure 7.18-3 The catabolism of various molecules from food (step 3) Acetyl CoA 106

Amino acids Fatty acids Citric acid cycle Figure 7.18-4 Proteins Carbohydrates Fats Amino acids Sugars Glycerol Fatty acids Glycolysis Glucose Glyceraldehyde 3- P NH3 Pyruvate Figure 7.18-4 The catabolism of various molecules from food (step 4) Acetyl CoA Citric acid cycle 107

Amino acids Fatty acids Citric acid cycle Oxidative phosphorylation Figure 7.18-5 Proteins Carbohydrates Fats Amino acids Sugars Glycerol Fatty acids Glycolysis Glucose Glyceraldehyde 3- P NH3 Pyruvate Figure 7.18-5 The catabolism of various molecules from food (step 5) Acetyl CoA Citric acid cycle Oxidative phosphorylation 108

Biosynthesis (Anabolic Pathways) The body uses small molecules to build other substances Some of these small molecules come directly from food; others can be produced during glycolysis or the citric acid cycle © 2014 Pearson Education, Inc. 109

Figure 7.UN10a Figure 7.UN10a Skills exercise: making a bar graph and interpreting the data (part 1) 110

Figure 7.UN10b Figure 7.UN10b Skills exercise: making a bar graph and interpreting the data (part 2) 111

Inputs Glycolysis Glucose ATP  2 NADH Figure 7.UN11 Inputs Outputs Glycolysis Glucose 2 Pyruvate  2 ATP  2 NADH Figure 7.UN11 Summary of key concepts: pyruvate 112

CO2 Inputs Outputs 2 Pyruvate 2 Acetyl CoA 2 ATP 8 NADH Citric acid Figure 7.UN12 Inputs Outputs 2 Pyruvate 2 Acetyl CoA 2 ATP 8 NADH Citric acid cycle 2 Oxaloacetate CO2 6 2 FADH2 Figure 7.UN12 Summary of key concepts: citric acid cycle 113

(carrying electrons from food) Figure 7.UN13a INTERMEMBRANE SPACE H H Protein complex of electron carriers H Cyt c IV Q III I Figure 7.UN13a Summary of key concepts: oxidative phosphorylation (part 1) II 2 H  ½O2 H2O FADH2 FAD NADH NAD MITOCHONDRIAL MATRIX (carrying electrons from food) 114

INTER- MEMBRANE SPACE H MITO- ATP CHONDRIAL synthase MATRIX ADP  ATP Figure 7.UN13b INTER- MEMBRANE SPACE H MITO- CHONDRIAL MATRIX ATP synthase Figure 7.UN13b Summary of key concepts: oxidative phosphorylation (part 2) ADP  P H ATP i 115

across membrane pH difference Figure 7.UN14 across membrane pH difference Figure 7.UN14 Test your understanding, question 8 (pH vs. time) Time 116