Cellular Respiration: Harvesting Chemical Energy Chapter 7

Fig. 9-1

Overview: Life Is Work Living cells require energy from outside sources Some animals, such as the giant panda, obtain energy by eating plants, and some animals feed on other organisms that eat plants Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Energy flows into an ecosystem as sunlight and leaves as heat Photosynthesis generates O 2 and organic molecules, which are used in cellular respiration Cells use chemical energy stored in organic molecules to regenerate ATP, which powers work Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 9-2 Light energy ECOSYSTEM Photosynthesis in chloroplasts CO 2 + H 2 O Cellular respiration in mitochondria Organic molecules + O 2 ATP powers most cellular work Heat energy ATP

Catabolic pathways yield energy by oxidizing organic fuels Several processes are central to cellular respiration and related pathways Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Catabolic Pathways and Production of ATP The breakdown of organic molecules is exergonic Fermentation is a partial degradation of sugars that occurs without O 2 Aerobic respiration consumes organic molecules and O 2 and yields ATP Anaerobic respiration is similar to aerobic respiration but consumes compounds other than O 2 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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: C 6 H 12 O O 2  6 CO H 2 O + Energy (ATP + heat) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Principle of Redox 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) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 9-UN1 becomes oxidized (loses electron) becomes reduced (gains electron)

Fig. 9-UN2 becomes oxidized becomes reduced

The electron donor is called the reducing agent The electron receptor 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 O 2 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 9-3 Reactants becomes oxidized becomes reduced Products Methane (reducing agent) Oxygen (oxidizing agent) Carbon dioxideWater

Oxidation of Organic Fuel Molecules During Cellular Respiration During cellular respiration, the fuel (such as glucose) is oxidized, and O 2 is reduced: What is the reducing agent and what is the oxidizing agent C 6 H 12 O O 2  6 CO H 2 O Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 9-UN3 becomes oxidized becomes reduced

The summary reaction for photosynthesis can be written as 6 CO H 2 O → C 6 H 12 O O 2 This type of reaction is an oxidation-reduction (or redox) reaction. This reaction is also [anabolic/catabolic] and [endergonic/exergonic].

Fig. 9-UN4 Dehydrogenase

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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 9-4 Dehydrogenase Reduction of NAD + Oxidation of NADH 2 e – + 2 H + 2 e – + H + NAD + + 2[H] NADH + H+H+ H+H+ Nicotinamide (oxidized form) Nicotinamide (reduced form)

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 O 2 pulls electrons down the chain in an energy- yielding tumble The energy yielded is used to regenerate ATP Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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Fig. 9-5 Free energy, G (a) Uncontrolled reaction H2OH2O H / 2 O 2 Explosive release of heat and light energy (b) Cellular respiration Controlled release of energy for synthesis of ATP 2 H e – 2 H + 1 / 2 O 2 (from food via NADH) ATP 1 / 2 O 2 2 H + 2 e – Electron transport chain H2OH2O

Fig Maximum per glucose: About 36 or 38 ATP + 2 ATP + about 32 or 34 ATP Oxidative phosphorylation: electron transport and chemiosmosis Citric acid cycle 2 Acetyl CoA Glycolysis Glucose 2 Pyruvate 2 NADH 6 NADH2 FADH 2 2 NADH CYTOSOL Electron shuttles span membrane or MITOCHONDRION

The Stages of Cellular Respiration: A Preview Cellular respiration has three stages: – Glycolysis (breaks down glucose into two molecules of pyruvate) – The citric acid cycle (completes the breakdown of glucose) – Oxidative phosphorylation (accounts for most of the ATP synthesis) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Substrate-level phosphorylation ATP Cytosol Glucose Pyruvate Glycolysis Electrons carried via NADH

Fig Mitochondrion Substrate-level phosphorylation ATP Cytosol Glucose Pyruvate Glycolysis Electrons carried via NADH Substrate-level phosphorylation ATP Electrons carried via NADH and FADH 2 Citric acid cycle

Fig Mitochondrion Substrate-level phosphorylation ATP Cytosol Glucose Pyruvate Glycolysis Electrons carried via NADH Substrate-level phosphorylation ATP Electrons carried via NADH and FADH 2 Oxidative phosphorylation ATP Citric acid cycle Oxidative phosphorylation: electron transport and chemiosmosis

The process that generates most of the ATP is called oxidative phosphorylation because it is powered by redox reactions Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 9-7 Enzyme ADP P Substrate Enzyme ATP + Product

Glycolysis harvests chemical energy by oxidizing glucose to pyruvate Glycolysis (“splitting of sugar”) breaks down glucose into two molecules of pyruvate Glycolysis occurs in the cytoplasm and has two major phases: – Energy investment phase – Energy payoff phase Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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Fig. 9-8 Energy investment phase Glucose 2 ADP + 2 P 2 ATPused formed 4 ATP Energy payoff phase 4 ADP + 4 P 2 NAD e – + 4 H + 2 NADH + 2 H + 2 Pyruvate + 2 H 2 O Glucose Net 4 ATP formed – 2 ATP used2 ATP 2 NAD e – + 4 H + 2 NADH + 2 H +

Fig ATP ADP Hexokinase 1 ATP ADP Hexokinase 1 Glucose Glucose-6-phosphate Glucose Glucose-6-phosphate

Fig Hexokinase ATP ADP 1 Phosphoglucoisomerase 2 Phosphogluco- isomerase 2 Glucose Glucose-6-phosphate Fructose-6-phosphate Glucose-6-phosphate Fructose-6-phosphate

1 Fig Hexokinase ATP ADP Phosphoglucoisomerase Phosphofructokinase ATP ADP 2 3 ATP ADP Phosphofructo- kinase Fructose- 1, 6-bisphosphate Glucose Glucose-6-phosphate Fructose-6-phosphate Fructose- 1, 6-bisphosphate Fructose-6-phosphate 3

Fig Glucose ATP ADP Hexokinase Glucose-6-phosphate Phosphoglucoisomerase Fructose-6-phosphate ATP ADP Phosphofructokinase Fructose- 1, 6-bisphosphate Aldolase Isomerase Dihydroxyacetone phosphate Glyceraldehyde- 3-phosphate Aldolase Isomerase Fructose- 1, 6-bisphosphate Dihydroxyacetone phosphate Glyceraldehyde- 3-phosphate 4 5

Fig NAD + NADH H + 2 2P i Triose phosphate dehydrogenase 1, 3-Bisphosphoglycerate 6 2 NAD + Glyceraldehyde- 3-phosphate Triose phosphate dehydrogenase NADH2 + 2 H + 2 P i 1, 3-Bisphosphoglycerate 6 2 2

Fig NAD + NADH 2 Triose phosphate dehydrogenase + 2 H + 2 P i 2 2 ADP 1, 3-Bisphosphoglycerate Phosphoglycerokinase 2 ATP 2 3-Phosphoglycerate ADP 2 ATP 1, 3-Bisphosphoglycerate 3-Phosphoglycerate Phosphoglycero- kinase 2 7

Fig Phosphoglycerate Triose phosphate dehydrogenase 2 NAD + 2 NADH + 2 H + 2 P i 2 2 ADP Phosphoglycerokinase 1, 3-Bisphosphoglycerate 2 ATP 3-Phosphoglycerate 2 Phosphoglyceromutase 2-Phosphoglycerate Phosphoglycero- mutase

Fig NAD + NADH H + Triose phosphate dehydrogenase 2 P i 1, 3-Bisphosphoglycerate Phosphoglycerokinase 2 ADP 2 ATP 3-Phosphoglycerate Phosphoglyceromutase Enolase 2-Phosphoglycerate 2 H 2 O Phosphoenolpyruvate Phosphoglycerate Enolase 2 2 H 2 O Phosphoenolpyruvate 9

Fig Triose phosphate dehydrogenase 2 NAD + NADH ADP 2 ATP Pyruvate Pyruvate kinase Phosphoenolpyruvate Enolase 2 H 2 O 2-Phosphoglycerate Phosphoglyceromutase 3-Phosphoglycerate Phosphoglycerokinase 2 ATP 2 ADP 1, 3-Bisphosphoglycerate + 2 H ADP 2 ATP Phosphoenolpyruvate Pyruvate kinase 2 Pyruvate 10 2 P i

The citric acid cycle completes the energy-yielding oxidation of organic molecules In the presence of O 2, pyruvate enters the mitochondrion Before the citric acid cycle can begin, pyruvate must be converted to acetyl CoA, which links the cycle to glycolysis Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig CYTOSOLMITOCHONDRION NAD + NADH+ H Pyruvate Transport protein CO 2 Coenzyme A Acetyl CoA

The citric acid cycle, also called the Krebs cycle, takes place within the mitochondrial matrix The cycle oxidizes organic fuel derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH 2 per turn Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Pyruvate NAD + NADH + H + Acetyl CoA CO 2 CoA Citric acid cycle FADH 2 FAD CO NAD H + ADP +P i ATP NADH

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 FADH 2 produced by the cycle relay electrons extracted from food to the electron transport chain Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Acetyl CoA Oxaloacetate CoA—SH 1 Citrate Citric acid cycle

Fig Acetyl CoA Oxaloacetate Citrate CoA—SH Citric acid cycle 1 2 H2OH2O Isocitrate

Fig Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Citric acid cycle Isocitrate NAD + NADH + H +  -Keto- glutarate CO2CO2

Fig Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + Citric acid cycle  -Keto- glutarate CoA—SH NAD + NADH + H + Succinyl CoA CO2CO2 CO2CO2

Fig Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2 Citric acid cycle CoA—SH  -Keto- glutarate CO2CO2 NAD + NADH + H + Succinyl CoA CoA—SH GTP GDP ADP P i Succinate ATP

Fig Acetyl CoA CoA—SH Oxaloacetate H2OH2O Citrate Isocitrate NAD + NADH + H + CO2CO2 Citric acid cycle CoA—SH  -Keto- glutarate CO2CO2 NAD + NADH + H + CoA—SH P Succinyl CoA i GTP GDP ADP ATP Succinate FAD FADH 2 Fumarate

Fig Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2  -Keto- glutarate CoA—SH NAD + NADH Succinyl CoA CoA—SH PP GDP GTP ADP ATP Succinate FAD FADH 2 Fumarate Citric acid cycle H2OH2O Malate i CO2CO2 + H + 3 4

Fig Acetyl CoA CoA—SH Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2  -Keto- glutarate CoA—SH CO2CO2 NAD + NADH + H + Succinyl CoA CoA—SH P i GTP GDP ADP ATP Succinate FAD FADH 2 Fumarate Citric acid cycle H2OH2O Malate Oxaloacetate NADH +H + NAD

During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis Following glycolysis and the citric acid cycle, NADH and FADH 2 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Pathway of Electron Transport The electron transport chain is in the 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 O 2, forming H 2 O Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig NADH NAD + 2 FADH 2 2 FAD Multiprotein complexes FAD FeS FMN FeS Q  Cyt b   Cyt c 1 Cyt c Cyt a Cyt a 3 IVIV Free energy (G) relative to O 2 (kcal/mol) (from NADH or FADH 2 ) 0 2 H / 2 O2O2 H2OH2O e–e– e–e– e–e–

Electrons are transferred from NADH or FADH 2 to the electron transport chain Electrons are passed through a number of proteins including cytochromes (each with an iron atom) to O 2 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Maximum per glucose: About 36 or 38 ATP + 2 ATP + about 32 or 34 ATP Oxidative phosphorylation: electron transport and chemiosmosis Citric acid cycle 2 Acetyl CoA Glycolysis Glucose 2 Pyruvate 2 NADH 6 NADH2 FADH 2 2 NADH CYTOSOL Electron shuttles span membrane or MITOCHONDRION

Fig Protein complex of electron carriers H+H+ H+H+ H+H+ Cyt c Q    VV FADH 2 FAD NAD + NADH (carrying electrons from food) Electron transport chain 2 H / 2 O 2 H2OH2O ADP + P i Chemiosmosis Oxidative phosphorylation H+H+ H+H+ ATP synthase ATP 21

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Fig INTERMEMBRANE SPACE Rotor H+H+ Stator Internal rod Cata- lytic knob ADP + P ATP i MITOCHONDRIAL MATRIX

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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

An Accounting of ATP Production by Cellular Respiration During cellular respiration, most energy flows in this sequence: glucose  NADH  electron transport chain  proton-motive force  ATP About 40% of the energy in a glucose molecule is transferred to ATP during cellular respiration, making about 38 ATP Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fermentation and anaerobic respiration enable cells to produce ATP without the use of oxygen Most cellular respiration requires O 2 to produce ATP Glycolysis can produce ATP with or without O 2 (in aerobic or anaerobic conditions) In the absence of O 2, glycolysis couples with fermentation or anaerobic respiration to produce ATP Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Anaerobic respiration uses an electron transport chain with an electron acceptor other than O 2, for example sulfate Fermentation uses phosphorylation instead of an electron transport chain to generate ATP Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Types of Fermentation Fermentation consists of glycolysis plus reactions that regenerate NAD +, which can be reused by glycolysis Two common types of Fermentation -Alcohol fermentation -Lactic acid fermentation Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

In alcohol fermentation, pyruvate is converted to ethanol in two steps, with the first releasing CO 2 Alcohol fermentation by yeast is used in brewing, winemaking, and baking Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig ADP + 2PiPi 2 ATP Glucose Glycolysis 2 NAD + 2 NADH 2 Pyruvate + 2 H + 2 Acetaldehyde 2 Ethanol (a) Alcohol fermentation 2 ADP + 2 PiPi 2 ATP GlucoseGlycolysis 2 NAD + 2 NADH + 2 H + 2 Pyruvate 2 Lactate (b) Lactic acid fermentation 2 CO 2

Fig. 9-18a 2 ADP + 2 P i 2 ATP GlucoseGlycolysis 2 Pyruvate 2 NADH2 NAD H + CO 2 2 Acetaldehyde 2 Ethanol (a) Alcohol fermentation 2

In lactic acid fermentation, pyruvate is reduced to NADH, forming lactate as an end product, with no release of CO 2 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 O 2 is scarce Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 9-18b Glucose 2 ADP + 2 P i 2 ATP Glycolysis 2 NAD + 2 NADH + 2 H + 2 Pyruvate 2 Lactate (b) Lactic acid fermentation

Fermentation and Aerobic Respiration Compared Both processes use glycolysis to oxidize glucose and other organic fuels to pyruvate The processes have different final electron acceptors: an organic molecule (such as pyruvate or acetaldehyde) in fermentation and O 2 in cellular respiration Cellular respiration produces 38 ATP per glucose molecule; fermentation produces 2 ATP per glucose molecule Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Obligate anaerobes carry out fermentation or anaerobic respiration and cannot survive in the presence of O 2 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Glucose Glycolysis Pyruvate CYTOSOL No O 2 present: Fermentation O 2 present: Aerobic cellular respiration MITOCHONDRION Acetyl CoA Ethanol or lactate Citric acid cycle

The Evolutionary Significance of Glycolysis Glycolysis occurs in nearly all organisms Glycolysis probably evolved in ancient prokaryotes before there was oxygen in the atmosphere Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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; amino groups can feed glycolysis or the citric acid cycle Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fats are digested to glycerol (used in glycolysis) and fatty acids (used in generating acetyl CoA) 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Proteins Carbohydrates Amino acids Sugars Fats GlycerolFatty acids Glycolysis Glucose Glyceraldehyde-3- Pyruvate P NH 3 Acetyl CoA Citric acid cycle Oxidative phosphorylation

Biosynthesis (Anabolic Pathways) The body uses small molecules to build other substances These small molecules may come directly from food, from glycolysis, or from the citric acid cycle Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Regulation of Cellular Respiration via Feedback Mechanisms Feedback inhibition is the most common mechanism for control If ATP concentration begins to drop, respiration speeds up; when there is plenty of ATP, respiration slows down Control of catabolism is based mainly on regulating the activity of enzymes at strategic points in the catabolic pathway Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Glucose Glycolysis Fructose-6-phosphate Phosphofructokinase Fructose-1,6-bisphosphate Inhibits AMP Stimulates Inhibits Pyruvate Citrate Acetyl CoA Citric acid cycle Oxidative phosphorylation ATP + – –

Fermentation model Pi ATP pyruvate ethyl alcohol (or lactic acid) substrate-level phosphorylation glycolysis cytoplasm electrons protons glucose NAD+ NADH ADP

cellular respiration glucose electron transport chain oxygen mitochondria carbon dioxide inner mitochondrial membrane pyruvate outer mitochondrial membrane acetyl CoA H+ NAD+ electrons (e) NADH chemiosmosis FAD ATP synthase (proton pumps) FADH2 cristae ADP proton gradients Pi oxidative phosphorylation ATP substrate-level phosphorylation water oxidative phosphorylation