931 3121101 ext 2702 Power Point Lectures for

生物醫學暨環境生物學系 鄭智美 助理教授 第一教學大樓 931室 電話 3121101 - ext 2702 Power. Point Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Chapter 9 Cellular Respiration: Harvesting Chemical Energy 細胞呼吸: 能量的產生 Power. Point Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Key Concepts • Catabolic Pathways yield energy by oxidizing organic fuel • Glycolysis harvests chemical energy by oxidizing glucose to pyruvate • The citric Acid cycle completes the energy yielding oxidation of organic molecules • Chemiosmosis couples electron transport to ATP synthesis • Fermentation enables some cels to produce ATP without the use of oxygen • Glycolysis and citric acid cycle connect to many other metabolic pathways Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Overview: Life Is Work • Living cells – Require transfusions of energy from outside sources to perform their many tasks – Obtains energy for its cells by eating plants Figure 9. 1 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Energy flow and Chemical Recycling • Energy – Flows into an ecosystem as sunlight and leaves as heat Light energy ECOSYSTEM Photosynthesis in chloroplasts Organic CO 2 + H 2 O +O Cellular molecules 2 respiration in mitochondria AT P powers most cellular work Figure 9. 2 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Heat energ y

Catabolic pathways yield energy by oxidizing organic fuels • The breakdown of organic molecules is exergonic Organic compound+ O 2→CO 2+ H 2 O+Energy • To keep working – Cells must regenerate ATP Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Catabolic Pathways and Production of ATP • 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Redox Reactions: Oxidation and Reduction • Catabolic pathways yield energy – Due to the transfer of electrons Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The Principle of Redox • Redox reactions – Transfer electrons from one reactant to another by oxidation and reduction • In oxidation – A substance loses electrons, or is oxidized • In reduction – A substance gains electrons, or is reduced Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Examples of redox reactions becomes oxidized (loses electron) Na + Cl Na+ becomes reduced (gains electron) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings + Cl–

Methane combustion as an energy yielding redox reaction • Some redox reactions – Do not completely exchange electrons – Change the degree of electron sharing in covalent bonds Products Reactants becomes oxidized + CH 4 2 O 2 + 2 H 2 O Energy becomes reduced O O C O H O O H H H C + CO 2 H H Figure 9. 3 Methane (reducing agent) Oxygen (oxidizing agent) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Carbon dioxide Water

Oxidation of Organic Fuel Molecules During Cellular Respiration • During cellular respiration – Glucose is oxidized and oxygen is reduced becomes oxidized C 6 H 12 O 6 + 6 O 2 6 CO 2 + 6 H 2 O + Energy becomes reduced Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Stepwise Energy Harvest via NAD+ and the Electron Transport Chain • Cellular respiration – Oxidizes glucose in a series of steps Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

NAD+ as an electron shuttle • Electrons from organic compounds – Are usually first transferred to NAD+, a coenzyme 2 e– + 2 H + 2 e– + H + NAD+ Dehydrogenase O NH 2 H C N+ CH 2 O O– O P O HO O O HO CH 2 H O H HO H OH Nicotinamide (oxidized form) H OH N N H O C H N NH 2 + Nicotinamide (reduced form) • NADH, the reduced form of NAD+ NH 2 N N Reduction of NAD+ + 2[H] (from food) Oxidation of NADH – H Figure 9. 4 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Passes the electrons to the electron transport chain

The Uncontrolled Exergonic Reaction • If electron transfer is not stepwise – A large release of energy occurs – As in the reaction of hydrogen and oxygen to form water Free energy, G H 2 + 1/2 O 2 Figure 9. 5 A Explosive release of heat and light energy H 2 O Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings (a) Uncontrolled reaction

Cellulae Respiration 2 H • The electron transport chain Controlled release of energy for synthesis of ATP tron 2 O 2 1/ O 2 ATP trans ATP port Free energy, G 2 H+ + 2 e – n chai – Uses the energy from the electron transfer to form ATP 2 e– 2 H+ H 2 O Figure 9. 5 B Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 1/ (from food via NADH) Elec – Passes electrons in a series of steps instead of in one explosive reaction + (b) Cellular respiration 2

The Stages of Cellular Respiration: A Preview • Respiration is a cumulative function of three metabolic stages – 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

An overview of cellular respiration Electrons carried via NADH and FADH 2 Electrons carried via NADH Citric acid cycle Glycolsis Pyruvate Glucose Cytosol Mitochondrion ATP gure 9. 6 Substrate-level phosphorylation Oxidative phosphorylation: electron transport and chemiosmosis ATP Substrate-level phosphorylation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings ATP Oxidative phosphorylation

Substrate Level Phosphorylation • Both glycolysis and the citric acid cycle – Can generate ATP by substrate-level phosphorylation Enzyme ADP Substrate P Figure 9. 7 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings + Product ATP

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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Energy Input and Output of Glycolysis • Glycolysis consists of two major phases – Energy investment phase – Energy payoff phase Citric acid cycle Glycolysis ATP Oxidative phosphorylation ATP Energy investment phase Glucose 2 ATP + 2 P 2 ATP used Energy payoff phase 4 ADP + 4 P 2 NAD+ + 4 e- + 4 H + 4 ATP 2 NADH formed + 2 H+ 2 Pyruvate + 2 H 2 O Glucose 4 ATP formed – 2 ATP used Figure 9. 8 2 NAD+ + 4 e– + 4 H + Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2 Pyruvate + 2 H 2 O 2 ATP + 2 H+ 2 NADH

A closer look at the energy investment phase CH 2 OH H HO OH H OH Glycolysis Glucose ATP 1 Hexokinase ADP CH 2 OH P O H H H OH H HO H OH Glucose-6 -phosphate 2 Phosphoglucoisomerase CH 2 O P O HO H HO CH 2 OH HO Fructose-6 -phosphate 3 ATP Phosphofructokinase ADP P O CH 2 HO H OH H HO O Fructose 1, 6 -bisphosphate Aldolase P Figure 9. 9 A O CH 2 O C CH 2 OH Dihydroxyacetone phosphate 5 Isomerase P 4 H C O CHOH CH 2 O Glyceraldehyde 3 -phosphate Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings P Citric acid cycle Oxidative phosphorylation

A closer look at the energy payoff phase 6 Triose phosphate dehydrogenase 2 NAD+ 2 2 P Pi 2 NADH + 2 H+ O CHOH P CH 2 O 1, 3 -Bisphoglycerate 2 ADP 7 Phosphoglycerokinase 2 ATP O– 2 C CHOH O CH 2 3 -Phosphoglycerate 8 P Phosphoglyceromutase O– 2 C H 2 O 2 O C O P CH 2 OH 2 -Phosphoglycerate 9 Enolase O– C C O O P CH 2 Phosphoenolpyruvate 2 ADP 10 Pyruvate kinase 2 ATP 2 Figure 9. 8 B O– C O CH 3 Pyruvate Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The citric acid cycle completes the energy-yielding oxidation of organic molecules The citric acid cycle – Takes place in the matrix of the mitochondrion Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Conversion of pyruvate to Acetyl Co. A, the junction beween glycolysis and the citric acid cycle • Before the citric acid cycle can begin – Pyruvate must first be converted to acetyl Co. A, which links the cycle to glycolysis CYTOSOL MITOCHONDRION NAD+ NADH + H+ O– S Co. A C O 2 C C O O 1 3 CH 3 Pyruvate Transport protein Figure 9. 10 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings CH 3 Acetyle Co. A CO 2 Coenzyme A

An overview of the citric acid cycle Pyruvate (from glycolysis, 2 molecules per glucose) Glycolysis Citric acid cycle ATP Oxidative phosphorylation ATP CO 2 Co. A NADH + 3 H+ Acetyle Co. A Citric acid cycle FADH 2 FAD 2 CO 2 3 NAD+ 3 NADH + 3 H+ ADP + P i ATP Figure 9. 11 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

A closer look at the citric acid cycle Glycolysis Citric Oxidative acid phosphorylation cycle S Co. A C O CH 3 Acetyl Co. A SH O NADH + H+ C COO– 1 CH 2 8 Oxaloacetate HO C CH 2 COO– HO CH COO– CH 2 COO– NAD+ H 2 O COO– CH 2 2 HC COO– Malate HO Citrate Isocitrate COO– H 2 O Citric acid cycle 7 COO– CH CO 2 3 NAD+ COO– Fumarate HC CH COO– CH 2 Co. A SH 6 Co. A SH COO– FAD CH 2 C O COO– Succinate Pi S Co. A GTP GDP Succinyl Co. A ADP ATP Figure 9. 12 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 4 C O COO– CH 2 5 CH 2 FADH 2 COO– NAD+ NADH + H+ a-Ketoglutarate CH 2 COO– NADH CO 2

During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis NADH and FADH 2 – Donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The Pathway of Electron Transport • In the electron transport chain – Electrons from NADH and FADH 2 lose energy in several steps Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Free Energy Change During Electron Transport • At the end of the chain – Electrons are passed to oxygen, forming water 50 NADH Free energy (G) relative to O 2 (kcl/mol) FADH 2 40 I FMN Multiprotein complexes FAD Fe • S II O III Cyt b 30 Fe • S Cyt c 1 IV Cyt c Cyt a 3 20 10 0 Figure 9. 13 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2 H + + 1 2 O 2 H 2 O

Chemiosmosis: The Energy-Coupling Mechanism • ATP synthase – Is the enzyme that actually makes ATP INTERMEMBRANE SPACE H+ H+ A stator anchored in the membrane holds the knob stationary. H+ ADP + Pi Figure 9. 14 MITOCHONDRIAL MATRIX Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings A rotor within the membrane spins clockwise when H+ flows past it down the H+ gradient. ATP A rod (for “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.

At certain steps along the electron transport chain Electron transfer causes protein complexes to pump H+ from the mitochondrial matrix to the intermembrane space • The resulting H+ gradient – Stores energy – Drives chemiosmosis in ATP synthase – Is referred to as a proton-motive force Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Chemiosmosis – Is an energy-coupling mechanism that uses energy in the form of a H+ gradient across a membrane to drive cellular work Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Chemiosmosis and the electron transport chain Oxidative phosphorylation. electron transport and chemiosmosis Glycolysis ATP Inner Mitochondrial membrane ATP H+ H+ H+ Intermembrane space Protein complex of electron carners Q I Inner mitochondrial membrane IV III II FADH 2 NADH+ Mitochondrial matrix H+ Cyt c FAD+ NAD+ 2 H+ + 1/2 O 2 ATP synthase H 2 O ADP + (Carrying electrons from, food) ATP Pi H+ Chemiosmosis Electron transport chain + ATP synthesis powered by the flow Electron transport and pumping of protons (H ), + + which create an H gradient across the membrane Of H back across the membrane Figure 9. 15 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Oxidative phosphorylation

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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

There are three main processes in this metabolic enterprise Electron shuttles span membrane CYTOSOL MITOCHONDRION 2 NADH or 2 FADH 2 2 NADH Glycolysis Glucose 2 Pyruvate 6 NADH Citric acid cycle 2 Acetyl Co. A + 2 ATP by substrate-level phosphorylation Maximum per glucose: + 2 ATP by substrate-level phosphorylation About 36 or 38 ATP Figure 9. 16 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2 FADH 2 Oxidative phosphorylation: electron transport and chemiosmosis + about 32 or 34 ATP by oxidative phosphorylation, depending on which shuttle transports electrons from NADH in cytosol

Accounting of ATP production by cellular respiration • About 40% of the energy in a glucose molecule – Is transferred to ATP during cellular respiration, making approximately 38 ATP Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Fermentation enables some cells to produce ATP without the use of oxygen • Cellular respiration – Relies on oxygen to produce ATP • In the absence of oxygen – Cells can still produce ATP through fermentation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Glycolysis – Can produce ATP with or without oxygen, in aerobic or anaerobic conditions – Couples with fermentation to produce ATP Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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 CO 2 • In lactic acid fermentation – Pyruvate is reduced directly to NADH to form lactate as a waste product Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Fermentation 2 ADP + 2 P 1 2 ATP O– C O Glucose Glycolysis C O CH 3 2 Pyruvate 2 NAD+ 2 NADH H 2 CO 2 H H C O CH 3 2��� Ethanol 2 Acetaldehyde (a) Alcohol fermentation 2 ADP + 2 Glucose P 1 2 ATP Glycolysis O– C O O 2 NAD+ 2 NADH C OH CH 3 2 Lactate Figure 9. 17 (b) Lactic acid fermentation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings C O CH 3

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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Pyruvate is a key juncture in catabolism Glucose CYTOSOL Pyruvate No O 2 present Fermentation O 2 present Cellular respiration MITOCHONDRION Ethanol or lactate Figure 9. 18 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Acetyl Co. A Citric acid cycle

The Evolutionary Significance of Glycolysis • Glycolysis – Occurs in nearly all organisms – Probably evolved in ancient prokaryotes before there was oxygen in the atmosphere Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Glycolysis and the citric acid cycle connect to many other metabolic pathways Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The catabolism of various molecules from food Proteins • Catabolic pathways – Funnel electrons from many kinds of organic molecules into cellular respiration Amino acids Carbohydrates Sugars Glycolysis Glucose Glyceraldehyde-3 - P NH 3 Pyruvate Acetyl Co. A Citric acid cycle Figure 9. 19 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Oxidative phosphorylation Fats Glycerol Fatty acids

Biosynthesis (Anabolic Pathways) • The body – Uses small molecules to build other substances • These small molecules – May come directly from food or through glycolysis or the citric acid cycle Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Regulation of Cellular Respiration via Feedback Mechanisms Glucose Glycolysis • Cellular respiration – Is controlled by allosteric enzymes at key points in glycolysis and the citric acid cycle Fructose-6 -phosphate – Inhibits Phosphofructokinase Stimulates + – Fructose-1, 6 -bisphosphate Inhibits Pyruvate ATP Acetyl Co. A Citric acid cycle Figure 9. 20 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings AMP Oxidative phosphorylation Citrate