Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chapter 9 Cellular Respiration: Harvesting Chemical Energy 高醫生物醫學暨環境生物學系助理教授

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

Chapter 9Chapter 9

Cellular Respiration: Harvesting Chemical Energy

高醫生物醫學暨環境生物學系

助理教授張學偉

http://genomed.dlearn.kmu.edu.tw


• Energy

– Flows into an ecosystem as sunlight and leaves as heat Light energy

ECOSYSTEM

CO2 + H2O

Photosynthesisin chloroplasts

Cellular respiration

in mitochondria

Organicmolecules

+ O2

ATP

powers most cellular work

Heatenergy

Figure 9.2


• To keep working, cells must regenerate ATP

本圖補充


• An overview of cellular respiration

Figure 9.6

Electronscarried

via NADH

GlycolysisGlucos

ePyruvate

ATP

Substrate-levelphosphorylation

Electrons carried via NADH and

FADH2

Citric acid cycle

Oxidativephosphorylation:

electron transport and

chemiosmosis

ATPATP


Oxidativephosphorylation

MitochondrionCytosol


Concept

1: Catabolic pathways yield energy by oxidizing organic fuels

2: Glycolysis harvests energy by oxidizing glucose to pyruvate

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

4: During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis

5: Fermentation enables some cells to produce ATP without the use of oxygen

6: Glycolysis and the citric acid cycle connect to many other metabolic pathways


• Concept 9.1: Catabolic pathways yield energy by oxidizing organic fuels


Catabolic pathways ( 異化 ) yield energy by oxidizing organic fuels

同化作用

exergonic (產能的 ) endergonic 耗能的

Catabolic Pathways and Production of ATP

本圖為補充


• One catabolic process, fermentation (發酵 )

– Is a partial degradation of sugars that occurs without oxygen

Conecept 5: Fermentation enables some cells to produce ATP without the use of oxygen

稍後再講


• Cellular respiration

– Is the most prevalent and efficient catabolic pathway

– Consumes oxygen (with O2 as the ultimate electron acceptor) and organic molecules such as glucose

– Yields ATP

It is called cellular respiration to distinguish it from the respiration of breathing.


Redox Reactions: Oxidation and Reduction

• Catabolic pathways yield energy

– Due to the transfer of electrons

The Principle of Redox

• Redox reactions

– Transfer electrons from one reactant to another by oxidation and reduction


Definition of Oxidation & Reduction and its agent

• In oxidation

– A substance loses electrons, or is oxidized

• In reduction

– A substance gains electrons, or is reduced

Reducting Agent

Oxidating Agent

Na + Cl Na+ + Cl–

becomes oxidized(loses electron)

becomes reduced(gains electron)


• Some redox reactions

– Do not completely exchange electrons

– Change the degree of electron sharing in covalent bonds

CH4

H

H

HH

C O O O O OC

H H

Methane(reducingagent)

Oxygen(oxidizingagent)

Carbon dioxide Water

+ 2O2 CO2 + Energy + 2 H2O

becomes oxidized

becomes reduced

Reactants Products

Figure 9.3

注意 : blue ball 位置

注意 : blue ball 位置


Oxidation of Organic Fuel Molecules During Cellular Respiration

• During cellular respiration:

- Glucose is oxidized in a series of steps and oxygen is reduced

C6H12O6 + 6O2 6CO2 + 6H2O + Energy

becomes oxidized

becomes reduced

△G = - 686 Kcal

△G < 0 1. spontaneous reaction (without an input of energy)2. Liberating energy


NAD+

H

O

O

O O–

O

O O–

O

O

O

P

P

CH2

CH2

HO OHH

HHO OH

HO

H

H

N+

C NH2

HN

H

NH2

N

N

Nicotinamide(oxidized form)

NH2+ 2[H]

(from food)

Dehydrogenase

Reduction of NAD+

Oxidation of NADH

2 e– + 2 H+

2 e– + H+

NADH

OH H

N

C +

Nicotinamide(reduced form)

N

Figure 9.4

H+

H+

NAD+ = Nicotinamide adenine dinucleotide

Stepwise Energy Harvest via NAD+ and the Electron Transport Chain

adenine

• Nucleotide = Base + Sugar + Phosphate

• Nucleosides = Sugar + Base (no phosphate)


• Electrons from organic compounds

– Are usually first transferred to NAD+, a coenzyme

NAD+

H

O

O

O O–

O

O O–

O

O

O

P

P

CH2

CH2

HO OHH

HHO OH

HO

H

H

N+

C NH2

HN

H

NH2

N

N

Nicotinamide(oxidized form)

NH2+ 2[H]

(from food)

Dehydrogenase

Reduction of NAD+

Oxidation of NADH

2 e– + 2 H+

2 e– + H+

NADH

OH H

N

C +

Nicotinamide(reduced form)

N

Figure 9.4

H+

H+

Hydrogen atom

protonelectron

2 H 2H+ +2e- (oxidation) NAD+ + H+ +2e- NADH (reduction)= NAD+ + 2H NADH + H+


A is the electron donor (so it is oxidized) FAD & NAD(P) is the electron acceptor (so it is reduced).

The products of the reaction are B (oxidized state) FADH2 or NAD(P)H (reduced state) .

Ex. A B + 2H+ +2e- (oxidation)

(+) FAD + 2H+ +2e- FADH2 (reduction)

= A+ FAD <=> B+ FADH2

A+ FAD <=> B+ FADH2A+ NAD(P) <=> B+ NAD(P)H


圖形為補充

• NADH passes the electrons to the electron transport chain


• If electron transfer is not stepwise

– A large release of energy occurs

– As in the reaction of hydrogen and oxygen to form water

(a) Uncontrolled reaction

Fre

e en

ergy

, G

H2O

Explosiverelease of

heat and lightenergy

Figure 9.5 A

H2 + 1/2 O2


比較 The electron transport chain

• Passes electrons in a series of steps instead of in one explosive reaction

• Uses the energy from the electron transfer to form ATP

2 H 1/2 O2

(from food via NADH)

2 H+ + 2 e–

2 H+

2 e–

H2O

1/2 O2

Controlled release of energy for synthesis of

ATP ATP

ATP

ATPE

lectron

transp

ort ch

ain

Fre

e en

ergy

, G

(b) Cellular respiration

+

Figure 9.5 B


• An overview of cellular respiration

Figure 9.6

Electronscarried

via NADH

GlycolsisGlucos

ePyruvate

ATP



FADH2

Citric acid cycle



chemiosmosis

ATPATP




1 23


• 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


substrate-level phosphorylation

• generate ATP from glycolysis and TCA cycle

Figure 9.7

Enzyme Enzyme

ATP

ADP

Product

SubstrateP

+


• Concept 9.2: 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


• Glycolysis consists of two major phases

– Energy investment phase

– Energy payoff phase

Glycolysis Citricacidcycle


ATP ATP ATP

2 ATP

4 ATP

used

formed

Glucose

2 ATP + 2 P

4 ADP + 4 P

2 NAD+ + 4 e- + 4 H + 2 NADH + 2 H+

2 Pyruvate + 2 H2O

Energy investment phase

Energy payoff phase

Glucose 2 Pyruvate + 2 H2O

4 ATP formed – 2 ATP used 2 ATP

2 NAD+ + 4 e– + 4 H + 2 NADH

+ 2 H+

Net Rx

Net Rx: Glucose + 2ADP+ 2Pi + NAD+ 2 Pyruvate + 2ATP + 2NADH + 2 H+

Figure 9.8


Figure 9.9 A

investment phase

H H

H

HH

OHOH

HOOH

CH2O

H H

H

HO H

OH

HOOH

P

CH2O P

H

OH

HO

HO

HOH

CH2OH

P O CH2 O CH2 O P

HOH

HO

HOH

OP CH2

C O

CH2OH

H

C

CHOH

CH2

O

O P

ATP

ADP

Hexokinase

Glucose

Glucose-6-phosphate

Fructose-6-phosphate

ATP

ADP

Phosphoglucoisomerase

Phosphofructokinase

Fructose-1, 6-bisphosphate

Aldolase

Isomerase

1

2

3

4

5

O

H

OH

Dihydroxyacetonephosphate

Glyceraldehyde-3-phosphate

CH2OH

GlycolysisCitricacid

cycle


2 NAD+

NADH2+ 2 H+

Triose phosphatedehydrogenase

2 P i

2P C

CHOH

O

P

O

CH2 O

2 O–

1, 3-Bisphosphoglycerate2 ADP

2 ATP

Phosphoglycerokinase

CH2 O P

2

C

CHOH

3-Phosphoglycerate

Phosphoglyceromutase

O–

C

C

CH2OH

H O P

2-Phosphoglycerate

2 H2O

2 O–

Enolase

C

C

O

PO

CH2

Phosphoenolpyruvate2 ADP

2 ATP

Pyruvate kinase

O–

C

C

O

O

CH3

2

6

8

7

9

10

Pyruvate

O

Figure 9.8

payoff phase

KinaseisomeraseMutaseAldolaseenolaseDehydrogenase




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


• The citric acid cycle

– Takes place in the matrix of the mitochondrion


• Before citric acid cycle can begin

– Pyruvate must first be converted to acetyl CoA, which links the cycle to glycolysis

CYTOSOL MITOCHONDRION

NADH + H+NAD+

2

31

CO2 Coenzyme APyruvate

Acetyle CoA

S CoA

C

CH3

O

Transport protein

O–

O

O

C

C

CH3

Figure 9.10

From Vit B

Pyruvate Oxidation


• An overview of the citric acid cycle

ATP

2 CO2

3 NAD+

3 NADH

+ 3 H+

ADP + P i

FAD

FADH2

Citricacidcycle

CoA

CoA

Acetyle CoA

NADH+ 3 H+

CoA

CO2

Pyruvate(from glycolysis,2 molecules per glucose)

ATP ATP ATP

Glycolysis Citricacidcycle


Figure 9.11

= TCA (Tricarboxyl acid)

= Krebs Cycle


Acetyl CoA

NADH

Oxaloacetate

CitrateMalate

Fumarate

SuccinateSuccinyl

CoA

-Ketoglutarate

Isocitrate

Citricacidcycle

S CoA

CoA SH

NADH

NADH

FADH2

FAD

GTP GDP

NAD+

ADP

P i

NAD+

CO2

CO2

CoA SH

CoA SH

CoAS

H2O

+ H+

+ H+ H2O

C

CH3

O

O C COO–

CH2

COO–

COO–

CH2

HO C COO–

CH2

COO–

COO–

COO–

CH2

HC COO–

HO CHCOO–

CH

CH2

COO–

HO

COO–

CH

HC

COO–

COO–

CH2

CH2

COO–

COO–

CH2

CH2

C O

COO–

CH2

CH2

C O

COO–

1

2

3

4

5

6

7

8

Glycolysis Oxidativephosphorylation

NAD+

+ H+

ATP

Citricacidcycle

A closer look at the citric acid cycle

Figure 9.12


Figure 9.12

Acetyl CoA

NADH

Oxaloacetate

CitrateMalate

Fumarate

SuccinateSuccinyl

CoA

-Ketoglutarate

Isocitrate

Citricacidcycle

S CoA

CoA SH

NADH

NADH

FADH2

FAD

GTP GDP

NAD+

ADP

P i

NAD+

CO2

CO2

CoA SH

CoA SH

CoAS

H2O

+ H+

+ H+ H2O

C

CH3

O

O C COO–

CH2

COO–

COO–

CH2

HO C COO–

CH2

COO–

COO–

COO–

CH2

HC COO–

HO CHCOO–

CH

CH2

COO–

HO

COO–

CH

HC

COO–

COO–

CH2

CH2

COO–

COO–

CH2

CH2

C O

COO–

CH2

CH2

C O

COO–

1

2

3

4

5

6

7

8

Glycolysis Oxidativephosphorylation

NAD+

+ H+

ATP

Citricacidcycle

Figure 9.12

A closer look at the citric acid cycle

pyruvate

NAD + CoA NADH + CO2

3C 2C

6C

6C

5C

4C4C

4C

4C

4C

½ Glucose



Energetics

DHase


• Concept 9.4: During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis


An overview of cellular respiration

Figure 9.6

Electronscarried

via NADH

GlycolsisGlucose Pyruvate

ATP



FADH2

Citric acid cycle

Oxidativephosphorylation:electron transport

andchemiosmosis

ATPATP




• NADH and FADH2: Donate electrons to the electron transport chain (ETC), which powers ATP synthesis via oxidative phosphorylation


The Pathway of Electron Transport

• In the ETC

– Electrons from NADH and FADH2

lose energy in several steps

H2O

O2

NADH

FADH2

FMN

Fe•S Fe•S

Fe•S

O

FAD

Cyt b

Cyt c1

Cyt c

Cyt a

Cyt a3

2 H + + 12

I

II

III

IV

Multiproteincomplexes

0

10

20

30

40

50

Fre

e e

ner

gy

(G)

rela

tive

to O

2 (k

cl/m

ol)

Figure 9.13

• At the end of the chain

– Electrons are passed to oxygen, forming water


Chemiosmosis: The Energy-Coupling Mechanism

• ATP synthase is the enzyme that actually makes ATP

INTERMEMBRANE SPACE

H+

H+

H+

H+

H+

H+ H+

H+

P i

+ADP

ATP

A rotor within the membrane spins clockwise whenH+ flows past it down the H+

gradient.

A stator anchoredin the membraneholds the knobstationary.

A rod (for “stalk”)extending into the knob alsospins, activatingcatalytic sites inthe knob.

Three catalytic sites in the

stationary knobjoin inorganic Phosphate to ADPto make ATP.

MITOCHONDRIAL MATRIXFigure 9.14

注意 : H+& ATP的方向


• At certain steps along the electron transport chain

– Electron transfer causes protein complexes to pump H+ from the mitochondrial matrix to the intermembrane space. [逆反應 ; 與產生 ATP時的 H+運送方向相反 ]

目的 : resulting H+ gradient


• The resulting H+ gradient

– Stores energy

– Is referred to as a proton-motive force

– Drives chemiosmosis in ATP synthase

• Chemiosmosis

– Is an energy-coupling mechanism that uses energy in the form of a H+ gradient across a membrane to drive cellular work


Chemiosmosis & electron transport chain

Oxidativephosphorylation.electron transportand chemiosmosis

Glycolysis

ATP ATP ATP

InnerMitochondrialmembrane

H+

H+H+

H+

H+

ATPP i

Protein complexof electron carners

Cyt c

I

II

III

IV

(Carrying electronsfrom, food)

NADH+

FADH2

NAD+

FAD+ 2 H+ + 1/2 O2

H2O

ADP +

Electron transport chainElectron transport and pumping of protons (H+),

which create an H+ gradient across the membrane

ChemiosmosisATP synthesis powered by the flowOf H+ back across the membrane

ATPsynthase

Q

Oxidative phosphorylation

Intermembranespace

Innermitochondrialmembrane

Mitochondrialmatrix

Figure 9.15

NADH 3 ATP; FADH2 2 ATP


An Accounting of ATP Production by Cellular Respiration

Electron shuttlesspan membrane

CYTOSOL 2 NADH

2 FADH2

2 NADH 6 NADH 2 FADH22 NADH

Glycolysis

Glucose2

Pyruvate

2AcetylCoA

Citricacidcycle

Oxidativephosphorylation:electron transport

andchemiosmosis

MITOCHONDRION

by substrate-levelphosphorylation

by substrate-levelphosphorylation

by oxidative phosphorylation, dependingon which shuttle transports electronsfrom NADH in cytosol

Maximum per glucose:About

36 or 38 ATP

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

or

Figure 9.16


DHAP/GA3P shuttle

Malate/Asp shuttle

Shuttles for transfer of reducing equivalents from cytosol into mitochondria

補充不考


1 Pyruvate + NAD+ + CoASH 1 Acetyl-CoA + 1 NADH + CO2

TCA

Pyruvate Oxidation

Glycolysis Pyruvate Oxidation TCA 2 ATP2 NADH (2H)

2 (2x1) NADH

2 (2x1) GTP/ATP6 (2x3) NADH2 (2x1) FADH2

Glucose +2ADP + 2Pi+ 2NAD+ 2 pyruvate +2ATP+2NADH+2H++2H2O

2 Pyruvate + 2 NAD+ + 2 CoASH 2 Acetyl-CoA + 2 NADH + 2 CO2

Glycolysis (aerobic)

2 Acetyl-CoA + 4 H2O + 6 NAD+ + 2FAD + 2GDP + 2 Pi 2 CO2 + 6 NADH + 2 FADH2 + 2 CoA-SH + 2 GTP

aerobic


Glycolysis Pyruvate Oxidation TCA 2 ATP2 NADH (2H)

2 (2x1) NADH

2 (2x1) GTP/ATP6 (2x3) NADH2 (2x1) FADH2

EST & chemiosmosisNADH 3 ATP; FADH2 2 ATP

ATP 8 6 2 + 18 + 4 = 38 or (6) shuttle = 36

Glycolysis (aerobic)

• About 40% of the energy in a glucose molecule

– Is transferred to ATP during cellular respiration, making approximately 38 ATP


• Concept 9.5: 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 [no cellular respiration]

– Cells can still produce ATP through fermentation

• fermentation is a partial degradation of sugars that occurs without oxygen


• Glycolysis

– Can produce ATP with or without oxygen, in aerobic or anaerobic conditions

• Fermentation consists of

– Glycolysis + reactions that regenerate NAD+, which can be reused by glyocolysis


2 ADP + 2 P1 2 ATP

GlycolysisGlucose

2 NAD+ 2 NADH

2 Pyruvate

2 Acetaldehyde 2 Ethanol

(a) Alcohol fermentation

2 ADP + 2 P1 2 ATP

GlycolysisGlucose

2 NAD+ 2 NADH

2 Lactate

(b) Lactic acid fermentation

H

H OH

CH3

C

O –

OC

C O

CH3

H

C O

CH3

O–

C O

C O

CH3O

C O

C OHH

CH3

CO22

Figure 9.17

3C

2C

3C

3C

• alcohol fermentation

– Pyruvate is converted to ethanol in two steps, one of which releases CO2

• lactic acid fermentation

– Pyruvate is reduced directly to NADH to form lactate as a waste product

Types of Fermentation


• Anaerobic metabolism

Figure 9.6

Electronscarried

via NADH

GlycolsisGlucos

ePyruvate

ATP



FADH2

Citric acid cycle



chemiosmosis

ATPATP



MitochondrionCytosol lactate

Orethanol

2 1x2 32-34

23x22x2


• Pyruvate is a key juncture in catabolism

Glucose

CYTOSOL

Pyruvate

No O2 presentFermentation

O2 present Cellular respiration

Ethanolor

lactate

Acetyl CoA

MITOCHONDRION

Citricacidcycle

Figure 9.18


Summaries of Glycolysis

1. anaerobicGlucose -> 2 Lactate + 2 ATP (lactic acid fermentation)Glucose -> 2 Ethanol + 2 ATP (alcoholic fermentation)

2. aerobicGlucose -> 2 Pyruvate + 2ATP + 2NADH (aerobic subtotal)

註 : 2 NADH -> 6 ATP (aerobic conversion: 氧化磷酸化 )


Fermentation and Cellular Respiration Compared

• 相同點

Use glycolysis to oxidize glucose and other organic fuels to pyruvate

• 相異點1.Differ in their final electron acceptor

Fermentation by acetylaldehyde (ethanol ferment.); by pyruvate (lactate ferment.)

Cellular Respiration by O2

2.Cellular respiration produces more ATP


The Evolutionary Significance of Glycolysis

• Glycolysis

– Occurs in nearly all organisms

– Probably evolved in ancient prokaryotes before there was oxygen in the atmosphere


• Concept 9.6: Glycolysis and the citric acid cycle connect to many other metabolic pathways

The Versatility of Catabolism

• Catabolic pathways

– Funnel electrons from many kinds of organic molecules into cellular respiration


• The catabolism of various molecules from food

Amino acids

Sugars Glycerol Fattyacids

Glycolysis

Glucose

Glyceraldehyde-3- P

Pyruvate

Acetyl CoA

NH3

Citricacidcycle


FatsProteins Carbohydrates

Figure 9.19

-oxidation


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


Regulation of Cellular Respiration via Feedback Mechanisms

• Cellular respiration is controlled by allosteric enzymes (e.g., Phosphofructokinase) at key points in glycolysis and the citric acid cycle

Allosteric regulation (see glossary)The binding of a molecule to a protein that affects the function of the protein at a different site.

補充圖


• The control of cellular respirationGlucose

Glycolysis

Fructose-6-phosphate

Phosphofructokinase

Fructose-1,6-bisphosphateInhibits Inhibits

Pyruvate

ATPAcetyl CoA

Citricacidcycle

Citrate


Stimulates

AMP

+

– –

Figure 9.20

• ATP AMP + ppi

Documents

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chapter 9 Cellular Respiration: Harvesting Chemical Energy 高醫 生物醫學暨環境生物學系 助理教授

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chapter 9 Cellular Respiration: Harvesting Chemical Energy 高醫生物醫學暨環境生物學系助理教授