Fig. 9-1

Chapter 9 Cellular Respiration: Harvesting Chemical Energy

Chapter 9 Cellular Respiration: Harvesting Chemical Energy

• 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)

– Redox Reactions

Fig. 9-UN4

Dehydrogenase

Electrons from organic compounds are usually first transferred to NAD+, a coenzyme As an electron acceptor

Each NADH (the reduced form of NAD+) represents stored energy that is tapped to synthesize ATP

Fig. 9-4 NAD+ as an electron shuttle Dehydrogenase

Reduction of NAD+

Oxidation of NADH

2 e– + 2 H+

2 e– + H+

NAD+ + 2[H]

NADH

+

H+

H+

Nicotinamide(oxidized form)

Nicotinamide(reduced form)

Nicotinamide adenine dinucleotide, a derivative of the vitamin niacin

NADH passes the electrons to the electron transport chain

Fig. 9-2

Lightenergy

ECOSYSTEM

Photosynthesis in chloroplasts

CO2 + H2O

Cellular respirationin mitochondria

Organicmolecules+ O2

ATP powers most cellular work

Heatenergy

ATP

Fig. 9-5

Fre

e en

erg

y, G

Fre

e en

erg

y, G

(a) Uncontrolled reaction

H2O

H2 + 1/2 O2

Explosiverelease of

heat and lightenergy

(b) Cellular respiration

Controlledrelease ofenergy for

synthesis ofATP

2 H+ + 2 e–

2 H + 1/2 O2

(from food via NADH)

ATP

ATP

ATP

1/2 O22 H+

2 e–E

lectron

transp

ort

chain

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)

Fig. 9-6-1

Substrate-levelphosphorylation

ATP

Cytosol

Glucose Pyruvate

I. Glycolysis

Electronscarried

via NADH

Cellular respiration has three stages:

Fig. 9-6-2

Mitochondrion

Substrate-levelphosphorylation

ATP

Cytosol

Glucose Pyruvate

Glycolysis

Electronscarried

via NADH

Substrate-levelphosphorylation

ATP

Electrons carriedvia NADH and

FADH2

II.Citricacidcycle

Fig. 9-6-3

Mitochondrion

Substrate-levelphosphorylation

ATP

Cytosol

Glucose Pyruvate

Glycolysis

Electronscarried

via NADH

Substrate-levelphosphorylation

ATP

Electrons carriedvia NADH and

FADH2

Oxidativephosphorylation

ATP

Citricacidcycle

III. Oxidativephosphorylation:electron transport

andchemiosmosis

•The process that generates most of the ATP is called oxidative phosphorylation

• because it is powered by redox reactions

• Oxidative phosphorylation:

– accounts for almost 90% of the ATP generated by cellular respiration

• substrate-level phosphorylation

– A smaller amount of ATP is formed in glycolysis and the citric acid cycle by

ATP

Fig. 9-7

Enzyme

ADP

PSubstrate

Enzyme

ATP+

Product

Concept 9.2: 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

Fig. 9-8

Energy investment phase

Glucose

2 ADP + 2 P2 ATP

used

formed4 ATP

Energy payoff phase

4 ADP + 4 P

2 NAD+ + 4 e– + 4 H+ 2 NADH+ 2 H+

2 Pyruvate + 2 H2O

2 Pyruvate + 2 H2OGlucoseNet

4 ATP formed – 2 ATP used 2 ATP

2 NAD+ + 4 e– + 4 H+ 2 NADH + 2 H+

Fig. 9-9-1

ATP

ADP

Hexokinase1

ATP

ADP

Hexokinase1

Glucose

Glucose-6-phosphate

Glucose

Glucose-6-phosphate

Fig. 9-9-2

Hexokinase

ATP

ADP

1

Phosphoglucoisomerase2

Phosphogluco-isomerase

2

Glucose

Glucose-6-phosphate

Fructose-6-phosphate

Glucose-6-phosphate

Fructose-6-phosphate

1

Fig. 9-9-3

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

1

2

3

Fructose-6-phosphate

3

Fig. 9-9-4

Glucose

ATP

ADP

Hexokinase

Glucose-6-phosphate

Phosphoglucoisomerase

Fructose-6-phosphate

ATP

ADP

Phosphofructokinase

Fructose-1, 6-bisphosphate

Aldolase

Isomerase

Dihydroxyacetonephosphate

Glyceraldehyde-3-phosphate

1

2

3

4

5

Aldolase

Isomerase

Fructose-1, 6-bisphosphate

Dihydroxyacetonephosphate

Glyceraldehyde-3-phosphate

4

5

Fig. 9-9-52 NAD+

NADH2

+ 2 H+

2

2 P i

Triose phosphatedehydrogenase

1, 3-Bisphosphoglycerate

6

2 NAD+

Glyceraldehyde-3-phosphate

Triose phosphatedehydrogenase

NADH2

+ 2 H+

2 P i

1, 3-Bisphosphoglycerate

6

2

2

Fig. 9-9-62 NAD+

NADH2

Triose phosphatedehydrogenase

+ 2 H+

2 P i

2

2 ADP

1, 3-Bisphosphoglycerate

Phosphoglycerokinase2 ATP

2 3-Phosphoglycerate

6

7

2

2 ADP

2 ATP

1, 3-Bisphosphoglycerate

3-Phosphoglycerate

Phosphoglycero-kinase

2

7

Fig. 9-9-7

3-Phosphoglycerate

Triose phosphatedehydrogenase

2 NAD+

2 NADH+ 2 H+

2 P i

2

2 ADP

Phosphoglycerokinase

1, 3-Bisphosphoglycerate

2 ATP

3-Phosphoglycerate2

Phosphoglyceromutase

2-Phosphoglycerate2

2-Phosphoglycerate2

2

Phosphoglycero-mutase

6

7

8

8

Fig. 9-9-82 NAD+

NADH2

2

2

2

2

+ 2 H+

Triose phosphatedehydrogenase2 P i

1, 3-Bisphosphoglycerate

Phosphoglycerokinase

2 ADP

2 ATP

3-Phosphoglycerate

Phosphoglyceromutase

Enolase

2-Phosphoglycerate

2 H2O

Phosphoenolpyruvate

9

8

7

6

2 2-Phosphoglycerate

Enolase

2

2 H2O

Phosphoenolpyruvate

9

Fig. 9-9-9

Triose phosphatedehydrogenase

2 NAD+

NADH2

2

2

2

2

2

2 ADP

2 ATP

Pyruvate

Pyruvate kinase

Phosphoenolpyruvate

Enolase2 H2O

2-Phosphoglycerate

Phosphoglyceromutase

3-Phosphoglycerate

Phosphoglycerokinase

2 ATP

2 ADP

1, 3-Bisphosphoglycerate

+ 2 H+

6

7

8

9

10

2

2 ADP

2 ATP

Phosphoenolpyruvate

Pyruvate kinase

2 Pyruvate

10

2 P i

Concept 9.3: The citric acid cycle completes the energy-yielding oxidation of organic molecules

• In the presence of O2, pyruvate enters the mitochondrion

• Before the citric acid cycle can begin, pyruvate must be converted to acetyl CoA, which links the cycle to glycolysis

Fig. 9-10

CYTOSOL MITOCHONDRION

NAD+ NADH + H+

2

1 3

Pyruvate

Transport protein

CO2Coenzyme A

Acetyl CoA

Fig. 9-11

Pyruvate

NAD+

NADH

+ H+ Acetyl CoA

CO2

CoA

CoA

CoA

Citricacidcycle

FADH2

FAD

CO22

3

3 NAD+

+ 3 H+

ADP + P iATP

NADH

The cycle oxidizes organic fuel derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH2 per turn

also called the Krebs cycle

Fig. 9-12-1

Acetyl CoA

Oxaloacetate

CoA—SH

1

Citrate

Citricacidcycle

Fig. 9-12-2

Acetyl CoA

Oxaloacetate

Citrate

CoA—SH

Citricacidcycle

1

2

H2O

Isocitrate

Fig. 9-12-3

Acetyl CoA

CoA—SH

Oxaloacetate

Citrate

H2O

Citricacidcycle

Isocitrate

1

2

3

NAD+

NADH

+ H+

-Keto-glutarate

CO2

Fig. 9-12-4

Acetyl CoA

CoA—SH

Oxaloacetate

Citrate

H2O

IsocitrateNAD+

NADH

+ H+

Citricacidcycle

-Keto-glutarate

CoA—SH

1

2

3

4

NAD+

NADH

+ H+SuccinylCoA

CO2

CO2

Fig. 9-12-5

Acetyl CoA

CoA—SH

Oxaloacetate

Citrate

H2O

IsocitrateNAD+

NADH

+ H+

CO2

Citricacidcycle

CoA—SH -Keto-

glutarate

CO2NAD+

NADH

+ H+SuccinylCoA

1

2

3

4

5

CoA—SH

GTP GDP

ADP

P iSuccinate

ATP

Fig. 9-12-6

Acetyl CoA

CoA—SH

Oxaloacetate

H2O

CitrateIsocitrate

NAD+

NADH

+ H+

CO2

Citricacidcycle

CoA—SH -Keto-

glutarate

CO2NAD+

NADH

+ H+

CoA—SH

P

SuccinylCoA

i

GTP GDP

ADP

ATP

Succinate

FAD

FADH2

Fumarate

1

2

3

4

5

6

Fig. 9-12-7

Acetyl CoA

CoA—SH

Oxaloacetate

Citrate

H2O

IsocitrateNAD+

NADH

+ H+

CO2

-Keto-glutarate

CoA—SH

NAD+

NADH

SuccinylCoA

CoA—SH

PP

GDPGTP

ADP

ATP

Succinate

FAD

FADH2

Fumarate

CitricacidcycleH2O

Malate

1

2

5

6

7

i

CO2

+ H+

3

4

Fig. 9-12-8

Acetyl CoA

CoA—SH

Citrate

H2O

IsocitrateNAD+

NADH

+ H+

CO2

-Keto-glutarate

CoA—SH

CO2NAD+

NADH

+ H+SuccinylCoA

CoA—SH

P i

GTP GDP

ADP

ATP

Succinate

FAD

FADH2

Fumarate

CitricacidcycleH2O

Malate

Oxaloacetate

NADH

+H+

NAD+

1

2

3

4

5

6

7

8

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

The Pathway of Electron Transport

• 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 O2, forming H2O

Fig. 9-13

NADH

NAD+2FADH2

2 FADMultiproteincomplexesFAD

Fe•S

FMN

Fe•S

Q

Fe•S

Cyt b

Cyt c1

Cyt c

Cyt a

Cyt a3

IV

Fr e

e en

erg

y (G

) r e

lat i

ve t

o O

2 (

kcal

/mo

l)

50

40

30

20

10 2

(from NADHor FADH2)

0 2 H+ + 1/2 O2

H2O

e–

e–

e–

prothetic groups of cytochromes

flavin nucleotides (tightly bound to flavoproteins) :

determining the sequence of electron carrier by inhibitors:

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

Fig. 9-14

INTERMEMBRANE SPACE

Rotor

H+

Stator

Internalrod

Cata-lyticknob

ADP+P ATP

i

MITOCHONDRIAL MATRIX

model for ATP synthesis

• 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

Fig. 9-16

Protein complexof electroncarriers

H+

H+H+

Cyt c

Q

V

FADH2 FAD

NAD+NADH

(carrying electronsfrom food)

Electron transport chain

2 H+ + 1/2O2H2O

ADP + P i

Chemiosmosis

Oxidative phosphorylation

H+

H+

ATP synthase

ATP

21

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

Fig. 9-17

Maximum per glucose: About36 or 38 ATP

+ 2 ATP+ 2 ATP + about 32 or 34 ATP

Oxidativephosphorylation:electron transport

andchemiosmosis

Citricacidcycle

2AcetylCoA

Glycolysis

Glucose2

Pyruvate

2 NADH 2 NADH 6 NADH 2 FADH2

2 FADH2

2 NADHCYTOSOL Electron shuttles

span membrane

or

MITOCHONDRION

What about NADH from glycolysis?

• NADH made in cytosol

• Can’t get into matrix of mitochondrion

• 2 mechanisms

– In muscle and brain

• Glycerol phosphate shuttle

– In liver and heart

• Malate / aspartate shuttle

glycerol-3-phosphate shuttle : (used in skeletal muscle and brain)

In muscle and brain

Each NADH converted to FADH2 inside mitochondrion

FADH2 enters later in the electron transport chain produces 1.5 ATP

Total ATP per glucose in muscle and brain

• Gycerol phosphate shuttle

– 2 NADH per glucose - 2 FADH2

– 2 FADH2 X 1.5 ATP / FADH2……….3.0 ATP

– 2 ATP in glycoysis ……………2.0 ATP

– From pyruvate and Krebs

• 12.5 ATP X 2 per glucose …..25.0 ATP

Total = 30.0 ATP/ glucose

malate-aspartate shuttle : (used in liver, kidney and heart)

Malate – Aspartate Shuttle in cytosol

• In liver and heart

• NADH oxidized while reducing oxaloacetate to malate

– Malated dehydrogenase

• Malate crosses membrane

Malate – Aspartate Shuttle in matrix

• Malate reoxidized to oxaloacetate

– Malate dehydrogenase

– NAD+ reduced to NADH

• NADH via electron transport yields 2.5 ATP

Total ATP per glucose in liver and heart

• Malate – Aspartate Shuttle

– 2 NADH per glucose - 2 NADH

– 2 NADH X 2.5 ATP / NADH…………5.0 ATP

– 2 ATP from glycolysis………………..2.0 ATP

– From pyruvate and Krebs

• 12.5 ATP X 2 per glucose ……..25.0 ATP

• Total = 32.0 ATP/ glucose

Summary

• Total ATP / glucose

– Muscle and brain 30.0 ATP

• Uses glycerol phosphate shuttle

– Heart and liver 32.0 ATP

• Uses malate aspartate shuttle

Concept 9.5: Fermentation and anaerobic respiration enable cells to produce ATP withoutthe use of oxygen

• Most 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 or anaerobic respiration to produce ATP

Fig. 9-18

2 ADP + 2 Pi 2 ATP

Glucose Glycolysis

2 NAD+ 2 NADH

2 Pyruvate

+ 2 H+

2 Acetaldehyde2 Ethanol

(a) Alcohol fermentation

2 ADP + 2 Pi2 ATP

Glucose Glycolysis

2 NAD+ 2 NADH+ 2 H+

2 Pyruvate

2 Lactate

(b) Lactic acid fermentation

2 CO2

Fig. 9-19

Glucose

Glycolysis

PyruvateCYTOSOL

No O2 present:Fermentation

O2 present:

Aerobic cellular respiration

MITOCHONDRION

Acetyl CoAEthanolor

lactate Citricacidcycle

Fermentation and Aerobic Respiration Compared

•Glycolysis probably evolved in ancient prokaryotes before there was oxygen in the atmosphere

•Gycolysis and the citric acid cycle are major intersections to various catabolic and anabolic pathways

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

Fig. 9-20Proteins

Carbohydrates

Aminoacids

Sugars

Fats

Glycerol Fattyacids

Glycolysis

Glucose

Glyceraldehyde-3-

Pyruvate

P

NH3

Acetyl CoA

Citricacidcycle

Oxidativephosphorylation

Biosynthesis (Anabolic Pathways)

beta oxidation

•An oxidized gram of fat produces more than twice as much ATP as an oxidized gram of carbohydrate

•Catabolic pathways funnel electrons

•from many kinds of organic molecules into cellular respiration

Fig. 9-21Glucose

GlycolysisFructose-6-phosphate

Phosphofructokinase

Fructose-1,6-bisphosphateInhibits

AMP

Stimulates

Inhibits

Pyruvate

CitrateAcetyl CoA

Citricacidcycle

Oxidativephosphorylation

ATP

+

––

Regulation of Cellular Respiration via Feedback Mechanisms

1. Feedback inhibition is the most common mechanism for control

2. If ATP concentration begins to drop, respiration speeds up; when there is plenty of ATP, respiration slows down

3. Control of catabolism is based mainly on regulating the activity of enzymes at strategic points in the catabolic pathway

You should now be able to:

1. Name the three stages of cellular respiration; for each, state the region of the eukaryotic cell where it occurs and the products that result

2. In general terms, explain the role of the electron transport chain in cellular respiration

3. Explain where and how the respiratory electron transport chain creates a proton gradient