Chapter 9 – Cellular Respiration

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

Chapter 9 – Cellular Respiration

• Overview: Life Is Work

• Living cells

– Require transfusions of energy from outside sources to perform their many tasks

• Assemble polymers

• Pump substances against the membrane

• Move

• Reproduce


Cellular Respiration


Basics of Respiration

Biologists define respiration as the aerobic harvesting of energy from food molecules by cells


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

– Cells break down complex organic molecules (rich in potential energy) to simpler waste products (low in potential energy)

• To get energy to do work

• Rest is given off as heat


• Cells do this in two ways:

1) Fermentation

2) Cellular respiration


1) One catabolic process, fermentation

– Is a partial degradation of sugars that occurs without oxygen


2) Cellular respiration

– Most prevalent and efficient catabolic pathway

– Consumes oxygen and organic molecules such as glucose

– Yields more ATP


• The equation for the reaction of cellular respiration:

C6H12O6 + 6O2 6CO2 + 6H2O + Energy(ATP &

Heat)


Catabolic Pathways and Production of ATP

• The breakdown of organic molecules is exergonic

– But catabolic pathways don’t do work directly

• Just release energy so work can be done


Redox Reactions: Oxidation and Reduction

• Catabolic pathways yield energy

– Due to the transfer of electrons

– When 1 or more electrons transfers from one reactant to another the process is called oxidation reduction reaction or redox for short


The Principle of Redox

• Oxidation – loss of an electron

– The substance that gives up its electron is the reducing agent

• Reduction the gain of an electron

– The substance that gains the electron is the oxidizing agent


• Examples of redox reactions

Na + Cl Na+ + Cl–

becomes oxidized(loses electron)

Reducing agent

becomes reduced(gains electron)

Oxidizing agent


• Specifically in cellular respiration:

C6H12O6 + 6O2 6CO2 + 6H2O + Energy

becomes oxidized

becomes reduced

• Glucose is oxidized and oxygen is reduced

• Electrons lose potential energy and energy is released


To Sum Up

• Remember an electron loses potential energy when it shifts from a less electronegative atom to a more electronegative atom (oxygen is very electronegative)

• So by oxidizing glucose, respiration frees stored energy (in glucose) and makes it available for work (as ATP)


Stepwise Energy Harvest via NAD+ and the Electron Transport Chain

• Cellular respiration

– Oxidizes glucose in a series of steps

• Because energy can’t be released all at once and still be useful


Stepwise Energy Harvest

• Glucose is broken down in a series of steps with the help of enzymes

– First an electron is taken away from a glucose molecule. But a proton goes with the electron, so in effect a Hydrogen atom was removed

– Second it is picked up by a coenzyme NAD+ which will act as an oxidizing agent

• NAD+ is reduced to NADH



– Second it is picked up by a coenzyme NAD+ which will act as an oxidizing agent

• NAD+ is reduced to NADH

• Electrons lose little potential energy going from food to NAD+

• NADH molecule now represents stored energy



– Third NADH will release their electrons down a series of reactions with oxygen being the final electron acceptor (or receptor)

• This is known as the Electron Transport Chain and uses the energy from the electron transfer to form ATP


To Sum Up:

• The electrons removed from food by NAD+ fall down an energy gradient in the ETC to a far more stable location in the electronegative oxygen atom


The Stages of Cellular Respiration: A Preview

– Glycolysis

– The citric acid cycle

– Oxidative phosphorylation


• The first two stages are catabolic pathways that decompose glucose

1) Glycolysis

– Occurs in the cytosol

– Breaks down glucose into two molecules of pyruvate

2) The citric acid cycle

– Occurs in the mitochondrial matrix

– Completes the breakdown of glucose


Remember, why do we do this?

• Goal of cellular respiration is ATP production

1) Oxidative phosphorylation - redox rxns of the ETC

2) Substrate level phosphorylation


• Substrate level phosphorylation

– ATP is formed directly

• Enzymes transfer a phosphate group from a substrate molecule to an ADP (adenosine diphosphate)

– Generates ATP directly


• Both glycolysis and the citric acid cycle

– Can generate ATP by substrate-level phosphorylation

Figure 9.7

Enzyme Enzyme

ATP

ADP

Product

SubstrateP

+


• An overview of cellular respiration

Figure 9.6

Electronscarried

via NADH

GlycolsisGlucos

ePyruvate

ATP

Substrate-levelphosphorylation

Electrons carried via NADH and

FADH2

Citric acid cycle

Oxidativephosphorylation:

electron transport and

chemiosmosis

ATPATP

Substrate-levelphosphorylation

Oxidativephosphorylation

MitochondrionCytosol


Glycolysis

• Concept 9.2: Glycolysis harvests energy by oxidizing glucose to pyruvate

• Glycolysis

– Breaks down 1 glucose into 2 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+

Figure 9.8


• A closer look at the energy investment phase

– Be thinking:

• What do I start with?

• What do I add in to this?

• What do I get out of this?

• Where does this occur?



• A closer look at the energy payoff phase

– Be thinking:







Citric Acid Cycle

• 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 the citric acid cycle can begin:

– Pyruvate must first be converted to acetyl CoA, which links glycolysis to the citric acid cycleCYTOSOL 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

This only happens if oxygen is present!


1) The carboxyl group is removed (it is fully oxidized so it has little chemical energy left)

– First step where CO2 is releasedCYTOSOL MITOCHONDRION

NADH + H+NAD+

2

31


Acetyle CoA

S CoA

C

CH3

O

Transport protein

O–

O

O

C

C

CH3

Figure 9.10


2) Electrons are removed and transferred to NAD+ which stores them as NADH

CYTOSOL MITOCHONDRION

NADH + H+NAD+

2

31


Acetyle CoA

S CoA

C

CH3

O

Transport protein

O–

O

O

C

C

CH3

Figure 9.10


3) Coenzyme A attaches via an unstable bond, so compound is now highly reactive

CYTOSOL MITOCHONDRION

NADH + H+NAD+

2

31


Acetyle CoA

S CoA

C

CH3

O

Transport protein

O–

O

O

C

C

CH3

Figure 9.10


• 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


• A closer look at the citric acid cycle

– Be thinking:






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


Oxidative Phosphorylation . . . ETC

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

• So far, only 4 ATP have been made


The Pathway of Electron Transport

• Electron Transport Chain – is a collection of molecules embedded in the inner membrane of the mitochondria

– Most components are proteins


• An NADH molecule begins the process by “dropping off” its electron at the first electron carrier molecule

H2O

O2

NADH

FADH2

FMN

Fe•S Fe•S

Fe•S

O

FAD

Cyt b

Cyt c1Cyt c

Cyt aCyt 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


• Remember: each component will be reduced when it accepts the electron and oxidized when it passes the electron down to the more electronegative carrier molecule in the chain

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


0

10

20

30

40

50

Fre

e e

ner

gy

(G)

rela

tive

to O

2 (k

cl/m

ol)

Figure 9.13


• Finally the electron is passed to oxygen, which is very electronegative.

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


0

10

20

30

40

50

Fre

e e

ner

gy

(G)

rela

tive

to O

2 (k

cl/m

ol)

Figure 9.13

The oxygen also picks up 2 H+ ions from the aqueous solution and forms water


• FADH goes through mostly the same processes, except it drops off its electron at a lower point on the ETC

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


0

10

20

30

40

50

Fre

e e

ner

gy

(G)

rela

tive

to O

2 (k

cl/m

ol)

Figure 9.13


WARNING: The ETC makes no ATP directly!

The ETC releases energy in a step-wise series of reactions. It powers ATP synthesis via oxidative phosphorylation.

But it needs to be coupled with chemiosmosis to actually make ATP.


Chemiosmosis: The Energy-Coupling Mechanism

• Inner membrane of mitochondria has many protein complexes called ATP synthase

– ATP synthase – enzyme that makes ATP from ADP and inorganic phosphate

• It uses the energy of an existing gradient to do this.


• The existing gradient is the difference in H+ ion concentration on opposite sides of the inner membrane of the mitochondria

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


So what is this process called?

• Chemiosmosis – the process in which energy stored in the form of a hydrogen ion gradient across a membrane is used to drive cellular work (like the synthesis of ATP)


• It is the job of the ETC to create this H+ ion gradient


Glycolysis

ATP ATP ATP


H+

H+H+

H+

H+

ATPP i


Cyt c

I

II

III

IV


NADH+

FADH2

NAD+

FAD+ 2 H+ + 1/2 O2

H2O

ADP +




ATPsynthase

Q


Intermembranespace


Mitochondrialmatrix

Figure 9.15


• H+ ions are pumped into the intermembrane space by the ETC

– The H+ ions want to drift back into the matrix

• But they can only come into the matrix easily through ATP synthase channels


• The rushing of H+ ions through ATP synthase acts like water turning a water wheel

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

Result is that inorganic phosphate can be joined to ADP to make ATP


To Sum Up

Chemiosmosis is an energy coupling mechanism that uses energy stored in the form of a H+ gradient across a membrane to drive cellular work

In mitochondria, the energy for gradient formation comes from the exergonic redox reactions of the ETC and ATP synthesis is the work performed by ATP synthase


• Chemiosmosis and the electron transport chain


Glycolysis

ATP ATP ATP


H+

H+H+

H+

H+

ATPP i


Cyt c

I

II

III

IV


NADH+

FADH2

NAD+

FAD+ 2 H+ + 1/2 O2

H2O

ADP +




ATPsynthase

Q


Intermembranespace


Mitochondrialmatrix

Figure 9.15


• There is a problem though, when we try to account how much ATP is made from glucose (or any organic molecule)

We can not state exactly how many ATP come from each glucose because of 3 reasons . . .


1) The ETC and ATP synthase work together, but not 100% in synchronicity

So there isn’t an exact correlation between NADH (or FADH) and ATP production

1 NADH synthesizes 2.5 – 3.3 ATP (

1 FADH synthesizes 1.5 – 2 ATP


2) The electron shuttle into the mitochondria can vary (either NAD+ or FAD) at the transition stage


3) The H+ ion gradient does other things in the mitochondria, it is not just used for the synthesis of ATP


Bottom Line

• We’ll say there are 38 ATP:

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


An interesting note:

• Cellular respiration harvests about 40% of the energy in a glucose molecule

– This is perhaps the most efficient energy conversion known


In comparison:

• The most efficient cars only convert about 25% of the energy stored in gas into energy that moves the car


• Concept 9.5: Fermentation enables some cells to produce ATP without the use of oxygen


– Relies on oxygen to produce ATP

• In the absence of oxygen

– Cells can still produce ATP through fermentation

– Not as much ATP is made


• Glycolysis

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

– Couples with fermentation – an extension of glycolysis, to produce ATP


Types of Fermentation

• Fermentation consists of

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


Type 1

•In alcohol fermentation

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

– The second regenerates NAD+ so glycolysis can continue


Type 2

•During lactic acid fermentation

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

– No CO2 is produced


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 Contrasted

• Fermentation and cellular respiration

– Differ in their final electron acceptor


– Produces more ATP


• 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

Some organisms can produce ATP using either cellular respiration or fermentation. They are called facultative anaerobes.

Ex: our muscle cells


• 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


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


– Is controlled by allosteric enzymes at key points in glycolysis and the citric acid cycle

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Chapter 9 – Cellular Respiration