Chapter 9

Cellular Respiration: Harvesting Chemical Energy

PowerPoint Lectures for Biology, Seventh Edition
Neil Campbell and Jane Reece

Lectures by Chris Romero

Copyright 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Overview: Life Is Work

Living cells require energy from outside sources Some animals, such as the giant panda, obtain energy by eating plants; others feed on organisms that eat plants

Copyright 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright 2005 Pearson Education, Inc. publishing as Benjamin Cummings

 Energy flows into an ecosystem as sunlight and leaves as heat Photosynthesis generates oxygen and organic molecules, which are used in cellular respiration Cells use chemical energy stored in organic molecules to regenerate ATP, which powers work

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LE 9-2
Light energy
ECOSYSTEM

Photosynthesis in chloroplasts CO2 + H2O Cellular respiration in mitochondria Organic + O molecules 2

ATP powers most cellular work Heat energy

Concept 9.1: Catabolic pathways yield energy by oxidizing organic fuels

Several processes are central to cellular respiration and related pathways

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Catabolic Pathways and Production of ATP

The breakdown of organic molecules is exergonic Fermentation is a partial degradation of sugars that occurs without oxygen Cellular respiration consumes oxygen and organic molecules and yields ATP Although carbohydrates, fats, and proteins are all consumed as fuel, it is helpful to trace cellular respiration with the sugar glucose:
C6H12O6 + 6O2 6CO2 + 6H2O + Energy (ATP + heat)
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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

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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)
becomes oxidized (loses electron)

Xe-

Ye-

becomes reduced (gains electron)

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 The electron donor is called the reducing agent The electron receptor is called the oxidizing agent

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 Some redox reactions do not transfer electrons but change the electron sharing in covalent bonds An example is the reaction between methane and oxygen

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LE 9-3

Reactants becomes oxidized CH4 H + 2 O2 CO2

Products

Energy

2 H2O

becomes reduced

C H Methane (reducing agent)

Oxygen (oxidizing agent)

Carbon dioxide

Water

Oxidation of Organic Fuel Molecules During Cellular Respiration

During cellular respiration, the fuel (such as glucose) is oxidized and oxygen is reduced:
becomes oxidized

C6H12O6 + 6O2

6CO2 + 6H2O + Energy

becomes reduced

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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 2005 Pearson Education, Inc. publishing as Benjamin Cummings

LE 9-4

2 e + 2 H+

2 e + H+

NAD+
Dehydrogenase + 2[H] (from food) Nicotinamide (oxidized form)

NADH

H+

+ Nicotinamide (reduced form)

H+

 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 Oxygen pulls electrons down the chain in an energy-yielding tumble The energy yielded is used to regenerate ATP
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LE 9-5

H2 + 1/2 O2

2H (from food via NADH)

1 /2

O2

2 H+ + 2 e Free energy, G Free energy, G

Controlled release of energy for synthesis of ATP ATP

ATP ATP

Explosive release of heat and light energy

2 e 2 H+
1 /2

O2

H2O Uncontrolled reaction Cellular respiration

H2O

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) The process that generates most of the ATP is called oxidative phosphorylation because it is powered by redox reactions
[Animation listed on slide following figure]
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LE 9-6_1

Glycolysis Glucose Pyruvate

Cytosol

Mitochondrion

ATP Substrate-level phosphorylation

LE 9-6_2

Glycolysis Glucose Pyruvate

Citric acid cycle

Cytosol

Mitochondrion

ATP Substrate-level phosphorylation

ATP Substrate-level phosphorylation

LE 9-6_3

Electrons carried via NADH

Electrons carried via NADH and FADH2

Glycolysis Glucose Pyruvate

Citric acid cycle

Oxidative phosphorylation: electron transport and chemiosmosis

Cytosol

Mitochondrion

ATP Substrate-level phosphorylation

ATP Substrate-level phosphorylation

ATP Oxidative phosphorylation

Animation: Cell Respiration Overview

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 Oxidative phosphorylation accounts for almost 90% of the ATP generated by cellular respiration A small amount of ATP is formed in glycolysis and the citric acid cycle by substrate-level phosphorylation

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LE 9-7

Enzyme

Enzyme

ADP P Substrate Product + ATP

Concept 9.2: Glycolysis harvests 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

Animation: Glycolysis
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LE 9-8

Energy investment phase Glucose

2 ADP + 2 P
Glycolysis Citric acid cycle Oxidative phosphorylation

2 ATP used

Energy payoff phase

ATP ATP ATP

4 ADP + 4 P

4 ATP formed

2 NAD+ + 4 e + 4 H+

2 NADH + 2 H+ 2 Pyruvate + 2 H2O

Net

Glucose 4 ATP formed 2 ATP used

2 NAD+ + 4 e + 4 H+

2 Pyruvate + 2 H2O 2 ATP 2 NADH + 2 H+

LE 9-9a_1
Glycolysis Citric acid cycle Oxidation phosphorylation

Glucose ATP Hexokinase ADP

ATP

ATP

ATP

Glucose-6-phosphate

LE 9-9a_2
Glycolysis Citric acid cycle Oxidation phosphorylation

Glucose ATP Hexokinase ADP

ATP

ATP

ATP

Glucose-6-phosphate

Phosphoglucoisomerase

Fructose-6-phosphate ATP Phosphofructokinase ADP

Fructose1, 6-bisphosphate Aldolase

Isomerase

Dihydroxyacetone phosphate

Glyceraldehyde3-phosphate

LE 9-9b_1
2 NAD+ Triose phosphate dehydrogenase 2 NADH + 2 H+

1, 3-Bisphosphoglycerate 2 ADP

Phosphoglycerokinase 2 ATP

3-Phosphoglycerate

Phosphoglyceromutase

2-Phosphoglycerate

LE 9-9b_2
2 NAD+ Triose phosphate dehydrogenase 2 NADH + 2 H+

1, 3-Bisphosphoglycerate 2 ADP

Phosphoglycerokinase 2 ATP

3-Phosphoglycerate

Phosphoglyceromutase

2-Phosphoglycerate Enolase

2 H2O

Phosphoenolpyruvate 2 ADP

Pyruvate kinase 2 ATP

Pyruvate

Concept 9.3: The citric acid cycle completes the energy-yielding oxidation of organic molecules
Before the citric acid cycle can begin, pyruvate must be converted to acetyl CoA, which links the cycle to glycolysis

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LE 9-10

CYTOSOL

MITOCHONDRION

NAD+

NADH

+ H+

Acetyl Co A Pyruvate CO2 Coenzyme A

Transport protein

 The citric acid cycle, also called the Krebs cycle, takes place within the mitochondrial matrix The cycle oxidizes organic fuel derived from pyruvate, generating one ATP, 3 NADH, and 1 FADH2 per turn

Animation: Electron Transport

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LE 9-11
Pyruvate (from glycolysis, 2 molecules per glucose) NAD+ CO2 CoA
Glycolysis

Citric acid cycle

Oxidation phosphorylation

NADH + H+

ATP

ATP

ATP

Acetyl CoA CoA CoA

Citric acid cycle

FADH2 FAD ADP + P i ATP

2 CO2 3 NAD+ 3 NADH + 3 H+

 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

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LE 9-12_1
Glycolysis Citric acid cycle Oxidation phosphorylation

ATP

ATP

ATP

Acetyl CoA

H2O Oxaloacetate

Citrate

Isocitrate
Citric acid cycle

LE 9-12_2
Glycolysis Citric acid cycle Oxidation phosphorylation

ATP

ATP

ATP

Acetyl CoA

H2O Oxaloacetate

Citrate

Isocitrate
Citric acid cycle CO2

NAD+
NADH + H+ a-Ketoglutarate

NAD+ NADH + H+

CO2

Succinyl CoA

LE 9-12_3
Glycolysis Citric acid cycle Oxidation phosphorylation

ATP

ATP

ATP

Acetyl CoA

H2O Oxaloacetate

Citrate

Isocitrate
Citric acid cycle CO2

NAD+
NADH + H+ a-Ketoglutarate

Fumarate

FADH2 FAD Succinate GTP GDP ADP Pi Succinyl CoA NAD+ NADH + H+

CO2

ATP

LE 9-12_4
Glycolysis Citric acid cycle Oxidation phosphorylation

ATP

ATP

ATP

Acetyl CoA

NADH + H+ NAD+ Oxaloacetate

H2O

Malate

Citrate

Isocitrate
Citric acid cycle CO2

H2O Fumarate

NAD+
NADH + H+ a-Ketoglutarate

FADH2 FAD Succinate GTP GDP ADP Pi Succinyl CoA NAD+ NADH + H+

CO2

ATP

Concept 9.4: 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

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The Pathway of Electron Transport

The electron transport chain is in the cristae of the mitochondrion

Most of the chains 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 water

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LE 9-13

NADH
50 FADH2 Multiprotein complexes

Free energy (G) relative to O2 (kcal/mol)

40

FMN

I FeS Q

FAD FeS II III Cyt b

30

FeS
Cyt c1 Cyt c Cyt a Cyt a3 IV

Glycolysis

Citric acid cycle

Oxidative phosphorylation: electron transport and chemiosmosis

ATP

ATP

ATP

20

10

2 H+ + 1/2 O2

H2O

 The electron transport chain generates no ATP The chains function is to break the large freeenergy drop from food to O2 into smaller steps that release energy in manageable amounts

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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
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LE 9-14
INTERMEMBRANE SPACE H+ H+ H+ H+ A stator anchored in the membrane holds the knob stationary. H+

H+

A rotor within the membrane spins as shown when H+ flows past it down the H+ gradient.

H+

A rod (or stalk) extending into the knob also spins, activating catalytic sites in the knob. H+ Three catalytic sites in the stationary knob join inorganic phosphate to ADP to make ATP.

ADP + P ATP
i

MITOCHONDRAL 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

Animation: Fermentation Overview

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LE 9-15
Inner mitochondrial membrane
Glycolysis Citric acid cycle Oxidative phosphorylation: electron transport and chemiosmosis

ATP

ATP

ATP

H+ H+ H+ H+ Intermembrane space Protein complex of electron carriers Q I Inner mitochondrial membrane NADH + H+ (carrying electrons from food) Mitochondrial matrix Electron transport chain Electron transport and pumping of protons (H+), Which create an H+ gradient across the membrane Oxidative phosphorylation II FADH2 NAD+ FAD ADP + P i H+ Chemiosmosis ATP synthesis powered by the flow of H+ back across the membrane ATP III ATP synthase Cyt c

IV

2H+ + 1/2 O2

H2O

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 2005 Pearson Education, Inc. publishing as Benjamin Cummings

LE 9-16

CYTOSOL

Electron shuttles span membrane

MITOCHONDRION 2 NADH or 2 FADH2 2 NADH 6 NADH 2 FADH2

2 NADH

Glycolysis Glucose

2 Pyruvate

2 Acetyl CoA

Citric acid cycle

Oxidative phosphorylation: electron transport and chemiosmosis

+ 2 ATP by substrate-level phosphorylation

+ 2 ATP by substrate-level phosphorylation

+ about 32 or 34 ATP by oxidation phosphorylation, depending on which shuttle transports electrons form NADH in cytosol

Maximum per glucose:

About 36 or 38 ATP

Concept 9.5: Fermentation enables some cells to produce ATP without the use of oxygen
Cellular respiration requires O2 to produce ATP Glycolysis can produce ATP with or without O2 (in aerobic or anaerobic conditions) In the absence of O2, glycolysis couples with fermentation to produce ATP

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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

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 In alcohol fermentation, pyruvate is converted to ethanol in two steps, with the first releasing CO2 Alcohol fermentation by yeast is used in brewing, winemaking, and baking
Play

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LE 9-17a

2 ADP + 2 P i

2 ATP

Glucose

Glycolysis 2 Pyruvate 2 NAD+ 2 NADH + 2 H+ 2 CO2

2 Ethanol

2 Acetaldehyde

Alcohol fermentation

 In lactic acid fermentation, pyruvate is reduced to 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

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LE 9-17b

2 ADP + 2 P i

2 ATP

Glucose

Glycolysis

2 NAD+

2 NADH + 2 H+

2 CO2 2 Pyruvate

2 Lactate

Lactic acid fermentation

Fermentation and Cellular 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) in fermentation and O2 in cellular respiration Cellular respiration produces much more ATP

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 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

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LE 9-18 Glucose

CYTOSOL Pyruvate No O2 present Fermentation O2 present Cellular respiration

MITOCHONDRION Ethanol or lactate Acetyl CoA

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

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Concept 9.6: 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

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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 Fats are digested to glycerol (used in glycolysis) and fatty acids (used in generating acetyl CoA)

An oxidized gram of fat produces more than twice as much ATP as an oxidized gram of carbohydrate
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LE 9-19
Proteins

Carbohydrates

Fats

Amino acids

Sugars

Glycerol Fatty acids

Glycolysis Glucose

Glyceraldehyde-3- P

NH3

Pyruvate

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

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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

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LE 9-20
Glucose AMP Glycolysis Fructose-6-phosphate Inhibits Phosphofructokinase Stimulates +

Fructose-1,6-bisphosphate

Inhibits

Pyruvate ATP Acetyl CoA

Citrate

Citric acid cycle

Oxidative phosphorylation