How Cells Release Stored Energy Chapter 7

When Mitochondria Spin Their Wheels Impacts, Issues Video When Mitochondria Spin Their Wheels

ATP Is Universal Energy Source Photosynthesizers get energy from the sun Animals get energy second- or third-hand from plants or other organisms Regardless, the energy is converted to the chemical bond energy of ATP

Making ATP Plants make ATP during photosynthesis Cells of all organisms make ATP by breaking down carbohydrates, fats, and protein

Main Types of Energy-Releasing Pathways Anaerobic pathways Evolved first Don’t require oxygen Start with glycolysis in cytoplasm Completed in cytoplasm Aerobic pathways Evolved later Require oxygen Start with glycolysis in cytoplasm Completed in mitochondria

Main Types of Energy-Releasing Pathways Where pathways start and finish

Main Types of Energy-Releasing Pathways start (glycolysis) in cytoplasm start (glycolysis) in cytoplasm completed in cytoplasm completed in mitochondrion Anaerobic Energy-Releasing Pathways Aerobic Respiration

The Stages of Cellular Respiration C6H1206 + 6O2 6CO2 + 6H20 Harvesting of energy from glucose has three stages Glycolysis breaks down glucose into two molecules of pyruvate Pyruvate oxidation (acetyl Co-A) and the citric acid cycle (Krebs cylce) completes the breakdown of glucose Oxidative phosphorylation accounts for most of the ATP synthesis with the help of the electron transport chain 8

Electrons via NADH Glycolysis Glucose Pyruvate CYTOSOL MITOCHONDRION Figure 7.6-1 An overview of cellular respiration (step 1) ATP Substrate-level 9

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 10

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 11

Summary Equation for Aerobic Respiration Overview of aerobic respiration

Overview of Aerobic Respiration CYTOPLASM glucose ATP 2 ATP 4 Glycolysis e- + H+ (2 ATP net) 2 NADH 2 pyruvate e- + H+ 2 CO2 2 NADH e- + H+ 8 NADH 4 CO2 KrebsCycle e- + H+ 2 ATP 2 FADH2 e- Electron Transfer Phosphorylation 32 ATP H+ water e- + oxygen Typical Energy Yield: 36 ATP Overview of Aerobic Respiration

The Role of Coenzymes NAD+ and FAD accept electrons and hydrogen Become NADH and FADH2 Deliver electrons and hydrogen to the electron transfer chain

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 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) 15

The electron donor is called the reducing agent becomes oxidized (loses electron) becomes reduced (gains electron) Figure 7.UN01 In-text figure, NaCl redox reaction, p. 136 The electron donor is called the reducing agent The electron acceptor is called the oxidizing agent 16

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 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 18

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 19

(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 20

Glucose A simple sugar (C6H12O6) Atoms held together by covalent bonds

1.) Glycolysis: Two Stages Energy-requiring steps ATP energy activates glucose and its six-carbon derivatives Energy-releasing steps The products of the first part are split into three-carbon pyruvate molecules ATP and NADH form

Glycolysis Glycolysis Glycolysis Rap

Inputs Glycolysis Glucose ATP  2 NADH Outputs Glycolysis Glucose 2 Pyruvate  2 ATP  2 NADH Figure 7.UN11 Summary of key concepts: pyruvate 24

Glycolysis: Net Energy Yield Input Glucose 2 NAD+ 2ATP (energy requiring) 4ADP Output 2 pyruvate 2 NADH (energy releasing) 2ADP 4 ATP (net gain of 2 ATP)

2.) Prep Reaction / Citric Acid Cycle Preparatory reactions Pyruvate is oxidized into two-carbon acetyl units and carbon dioxide NAD+ is reduced

Preparatory Reactions pyruvate coenzyme A (CoA) NAD+ NADH O O carbon dioxide CoA acetyl-CoA

PREP REACTION Input Output 2 Pyruvate 2 Co-A 2 NAD 2 Acetyl Co-A 2 CO2 2 NADH

Preparatory Reactions Krebs Cycle (Citric Acid Cycle)

Preparatory Reactions Acetyl-CoA Formation pyruvate Preparatory Reactions coenzyme A NAD+ (CO2) NADH CoA acetyl-CoA Krebs Cycle CoA oxaloacetate citrate NAD+ NADH NADH NAD+ FADH2 NAD+ FAD NADH ADP + phosphate group ATP

Citric Acid Cycle (Krebs Cycle) 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 Completes the breakdown of acetyl CoA to CO2 The cycle oxidizes organic fuel derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH2 per molecule of acetyl-CoA. 31

Citric acid cycle Acetyl CoA 1 Oxaloacetate 2 Citrate Isocitrate 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) 32

Citric acid cycle Acetyl CoA 1 Oxaloacetate 2 Citrate Isocitrate 3 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) 33

Citric acid cycle Acetyl CoA 1 Oxaloacetate 2 Citrate Isocitrate 3 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 34

Citric acid cycle Acetyl CoA 1 Oxaloacetate 2 Citrate Isocitrate 3 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 35

Citric acid cycle Acetyl CoA 1 Oxaloacetate 2 Malate Citrate 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 36

Citric acid cycle Acetyl CoA 1 Oxaloacetate 8 2 Malate Citrate 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 37

Krebs Cycle =CoA acetyl-CoA CoA oxaloacetate citrate NADH H2O NAD+ H2O malate isocitrate NAD+ H2O O O NADH fumarate FADH2 a-ketoglutarate FAD NAD+ CoA O NADH succinate succinyl-CoA ADP + phosphate group ATP

The Krebs Cycle Overall Reactants Overall Products 2 Acetyl-CoA 6 NAD+ 2 FAD 2 ADP and Pi Overall Products 2 Coenzyme A 4 CO2 6 NADH 2 FADH2 2 ATP

CO2 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 40

Coenzyme Reductions during First Two Stages Glycolysis 2 NADH Preparatory reactions 2 NADH Krebs cycle 2 FADH2 + 6 NADH Total 2 FADH2 + 10 NADH

3.) Electron Transport Chain 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

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 43

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 44

Phosphorylation glycolysis e– KREBS CYCLE electron transfer glucose Phosphorylation ATP 2 PGAL ATP 2 NADH 2 pyruvate glycolysis 2 FADH2 2 CO2 e– 2 acetyl-CoA 2 NADH H+ H+ 2 6 NADH KREBS CYCLE ATP Krebs Cycle ATP H+ 2 FADH2 ATP H+ 4 CO2 36 ATP H+ H+ ADP + Pi electron transfer phosphorylation H+ H+ H+

Electron Transfer Chain Oxidative Phosphorylation OUTER COMPARTMENT H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ e- e- e- H+ H+ H+ ADP + Pi ATP NADH + H+ NAD+ + 2H+ FADH2 FAD + 2H+ 2H+ + 1/2 02 H2O Electron Transfer Chain ATP Synthase H+ INNER COMPARTMENT

Energy Harvest Varies NADH formed in cytoplasm cannot enter mitochondrion It delivers electrons to mitochondrial membrane Membrane proteins shuttle electrons to NAD+ or FAD inside mitochondrion Electrons given to FAD yield less ATP than those given to NAD+

H INTERMEMBRANE SPACE Stator Rotor Internal rod Catalytic knob ADP  Figure 7.13 ATP synthase, a molecular mill ADP  P ATP MITOCHONDRIAL MATRIX i 48

Importance of Oxygen Electron transport phosphorylation requires the presence of oxygen Oxygen withdraws spent electrons from the electron transfer chain, then combines with H+ to form water

Summary of Energy Harvest (per molecule of glucose) Glycolysis 2 ATP formed by substrate-level phosphorylation Krebs cycle and preparatory reactions Electron transport phosphorylation 32 ATP formed by oxidative phosphorylation If FADH2 (from glycolysis) 34 ATP formed by oxidative phosphorylation If NADH is used (from glycolysis)

Efficiency of Aerobic Respiration 686 kcal of energy are released 7.5 kcal are conserved in each ATP When 36 ATP form, 270 kcal (36 X 7.5) are captured in ATP Efficiency is 270 / 686 X 100 = 39 percent Most energy is lost as heat

Alternative Energy Sources

Amino acids Fatty acids Proteins Carbohydrates Fats Amino acids Sugars Glycerol Fatty acids Figure 7.18-1 The catabolism of various molecules from food (step 1) 53

Amino acids Fatty acids 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) 54

Amino acids Fatty acids 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 55

Amino acids Fatty acids Citric acid cycle 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 56

Amino acids Fatty acids Citric acid cycle Oxidative phosphorylation 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 57

Anaerobic Pathways Do not use oxygen Produce less ATP than aerobic pathways Two types Fermentation pathways Anaerobic electron transport

Fermentation Pathways Begin with glycolysis Do not break glucose down completely to carbon dioxide and water Yield only the 2 ATP from glycolysis Steps that follow glycolysis serve only to regenerate NAD+

Alcoholic Fermentation Fermentation pathways

Lactate Fermentation glycolysis C6H12O6 ATP 2 energy input 2 ADP 2 NAD+ 2 NADH 4 ATP 2 pyruvate energy output 2 ATP net lactate fermentation electrons, hydrogen from NADH 2 lactate

Anaerobic Electron Transport Carried out by certain bacteria Electron transfer chain is in bacterial plasma membrane Final electron acceptor is compound from environment (such as nitrate), not oxygen ATP yield is low

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 63

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 64