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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chapter 9 Cellular Respiration: Harvesting Chemical Energy

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Page 1: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Chapter 9

Cellular Respiration: Harvesting Chemical Energy

Page 2: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Life Is Work!• What kind of work is done by living cells?

– synthesis, active transport, movement, growth, reproduction, maintaining homeostasis

• Work requires energy – where does the energy come from?

– Cells harvest energy by using various metabolic pathways:

• Some pathways convert light energy to organic compounds = photosynthesis (that’s the next chapter!)

• Other pathways convert organic compounds to usable energy (ATP) and heat = respiration

Page 3: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

The flow of energy• 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

HeatenergyFigure 9.2

Page 4: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Harvesting stored energy• Organic compounds store energy in their arrangement

of atoms.

• To harvest that energy, a cell systematically breaks down complex organic molecules that are rich in potential energy to simpler waste products that have less energy

• Some of this energy can be used to do work (= usable energy), the rest is lost as heat

Efficiency = ___amount of usable energy___ x 100total amount of energy released

(usable energy + heat)

Page 5: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Harvesting stored energy• The chemical reactions involved are

catabolic pathways (metabolic pathways that release stored energy by breaking down complex molecules)

• Two major catabolic pathways:

o Fermentation – partial breakdown of sugar without oxygen

o Cellular respiration – complete breakdownof sugar with oxygen

o This is far more prevalent and efficient!

Page 6: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Harvesting stored energy• Respiration operates on the same principle as

combustion (using different mechanism at much lower temperature)Summary of overall process:organic compounds + oxygen carbon dioxide + water + energy

• Carbohydrates, fats, and proteins can all be processed and used as fuel, but main pathways use carbohydrates (glucose):

C6H12O6 + 6O2 6CO2 + 6H2O + energy (ATP + heat)

Page 7: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Harvesting stored energy• What is the important difference between

combustion and respiration?

– In combustion, all of the energy is released in one step (high heat & much energy is lost)

– In respiration, energy is released in many controlled steps to make ATP (less heat & less energy loss)

Page 8: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Catabolic Pathways and Production of ATP• The breakdown of glucose is exergonic

– G = – 686 kcal/mole)

– remember that negative value means that the products have less energy than the reactants.

Page 9: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Cellular respiration• Just as the energy released by combustion

of petroleum is transferred by the engine and drive shaft to make the wheels turn, respiration is linked to cellular work by a chemical drive shaft: ATP

• So what is the point of cellular respiration??

To make ATP!!

Page 10: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

The ATP Cycle• To keep working cells must regenerate ATP

• A working muscle cell recycles its ATP at a rate of about 10 million molecules per second!

Page 11: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

ATP Review• Recall that the three negatively charged

phosphate groups is an unstable, energy-storing arrangement (like charges repel)

• The chemical “spring” tends to “relax” by losing the terminal phosphate

Page 12: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Redox Reactions: Oxidation and Reduction• Catabolic pathways yield energy due to the

transfer of electrons

• Energy is released when electrons move closer to electronegative atoms

• Oxygen is the the one of the most electronegative elements around!

• Oxidation is the loss of electrons (becomes more positive)

• Reduction is the gain of electrons (becomes more negative)

Page 13: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Redox Reactions: Oxidation and Reduction• In a chemical reaction, when one substance is

oxidized (loses electrons), another must be reduced (gains electrons)!

– the electrons have to go somewhere!

• Redox reactions are the transfer electrons from one reactant to another by oxidation and reduction

– The substance that is oxidized is the reducing agent (by giving its electrons to something)

– The substance that is reduced is the oxidizing agent (by taking the electrons from something)

Page 14: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Redox Reactions: Oxidation and Reduction• Example of a redox reaction

Na + Cl Na+ + Cl–

becomes oxidized(loses electron)

becomes reduced(gains electron)

Oxidizing agent (takes electrons)

Reducing agent (gives up electrons)

Page 15: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Redox Reactions: Oxidation and Reduction• Some redox reactions

– Do not completely exchange electrons

– Change the degree of electron sharing in covalent bonds of molecules

CH4

H

H

HH

C O O O O OC

H H

Methane(reducing

agent)

Oxygen(oxidizing

agent)

Carbon dioxide Water

+ 2O2CO

2+ Energy + 2 H2O

becomes oxidized

becomes reduced

Reactants Products

Figure 9.3

Page 16: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Oxidation vs. Reduction

• Oxidation

– losing electrons

– removing H

– adding O2

– releases energy

– exergonic

– catabolic

• Reduction

– gaining electrons

– adding H

– removing O2

– stores energy

– endergonic

– anabolic

Page 17: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Oxidation of Organic Fuel Molecules During Cellular Respiration

• During cellular respiration

– Glucose is oxidized and oxygen is reduced

C6H12O6 + 6O2 6CO2 + 6H2O + Energybecomes oxidized

becomes reduced

C6H12O6 O2 CO2 H2O0 +1 -2 0 +4 -2 +1 -2

Page 18: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Stepwise energy harvest• During cellular respiration, electrons “fall” from

organic molecules to oxygen in a series of steps(= redox reactions)

• Organic molecules store energy because they have many C-H bonds which are a source of “hilltop” electrons which have the potential to “fall” closer to oxygen.

– Only the barrier of activation energy holds back the flood of electrons to a lower energy state. Without this barrier, glucose would combine spontaneously with O2

Body temperature is not enough to overcome this activation energy!

Page 19: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Stepwise electron transfer: overview

• As hydrogen atoms are stripped from glucose during respiration, electrons are transferred by:

– NAD+ (“taxi”)

– Electron Transport Chain (ETC) (“water slide”)

Page 20: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

NAD: taxi to the electron transport chain• NAD+ (nicotinamide adenine dinucleotide) is a

coenzyme

• Since it accepts electrons, it functions as an oxidizing agent

NAD+

H

O

OO O–

OO 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

• Dehydrogenase transfers 2 electronsand 1 H+ to NAD+, forming NADH

• The other H+ is released to the cytosol

Page 21: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Electron Transport Chain• NADH passes the

electrons to the electron transport chain

• The electron transport chain passes electrons in a series of stepsinstead of in one explosive reaction

• The ETC uses the energy from the electron transfer to make 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 ofATP ATP

ATP

ATP

Free

ene

rgy,

G

(b) Cellular respiration

+

Figure 9.5 B

Page 22: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Electron Transport Chain: Overview• The ETC consists of several carrier molecules,

mostly proteins, built into the inner membrane of amitochondrion.

• Electrons removed from food are “shuttled” by NADH (taxi!) to the “top” end of the chain.

• Electrons “fall” down the chain because each carrier molecule in the chain is more electronegative than the one before it.

• At the bottom end, oxygen (the most electronegative) captures these electrons along with hydrogen & forms water (water slide!).

Page 23: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

General “flow” of electrons

Food NADH ETC O2

Page 24: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

What if it’s not stepwise?• If electron transfer is not stepwise

• A large (explosive!) release of energy occurs

• Example: reaction of hydrogen and oxygen to form water

(a) Uncontrolled reaction

Free

ene

rgy,

G

H2O

Explosiverelease of

heat and lightenergy

Figure 9.5 A

H2 + 1/2 O2

Page 25: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Page 26: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Overview of Cellular Respiration:

• Glycolysis

– Breaks down glucose into two molecules of pyruvate

• Krebs Cycle (citric acid cycle)

– Completes the breakdown of glucose

• Electron transport chain

– Series of redox reactions releases energy

– Energy is used to generate most of the ATP (by oxidative phosphorylation & chemiosmosis)

Page 27: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

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 andchemiosmosis

ATPATP

Substrate-levelphosphorylation

Oxidativephosphorylation

MitochondrionCytosol

Page 28: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Two ways to make ATP:

1. Substrate-level phosphorylation

2. Oxidative phosphorylation

Page 29: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

Substrate-level phosphorylation occurs during glycolysis and Krebs Cycle enzyme transfers a phosphate group from a

substrate molecule to ADP (instead of getting it as free Pi from the surroundings)

Figure 9.7

Enzyme Enzyme

ATP

ADP

Product

SubstrateP

+

Page 30: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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Oxidative phosphorylation

• almost 90% of ATP generated this way

• powered by series of electron transfers(= redox reactions) through NADH and FADH2 and electron transport chain

Page 31: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

A closer look: Glycolysis• Glycolysis

– Means “splitting of sugar”

– Breaks down glucose (6-C) into pyruvate (3-C)

– Occurs in the cytoplasm of the cell

– Pathway consists of ten steps, each catalyzed by a specific enzyme

Page 32: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

A closer look: Glycolysis

• Glycolysis consists of two major phases:

Glycolysis Citricacidcycle

Oxidativephosphorylation

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

Energy investment phase

Energy payoff phase

Page 33: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

A closer look at the energy investment phase

Dihydroxyacetonephosphate

Glyceraldehyde-3-phosphate

HH

H

HH

OHOH

HO HO

CH2OHH H

H

HO H

OHHO OH

P

CH2O P

H

OH

HO

HO

HHOCH2OH

P O CH2O CH2 O P

HOH HO

HOH

OP CH2

C OCH2OH

HCCHOHCH2

O

O P

ATP

ADPHexokinase

Glucose

Glucose-6-phosphate

Fructose-6-phosphate

ATP

ADP

Phosphoglucoisomerase

Phosphofructokinase

Fructose-1, 6-bisphosphate

Aldolase

Isomerase

Glycolysis

1

2

3

4

5

CH2OHOxidative

phosphorylation

Citricacidcycle

Figure 9.9 A

Cell “spends” 2 ATPs to phosphorylatesugars (enzymes are kinases!)

Other enzymes rearrange sugar molecules to make them more reactive

This is where sugar is actually split!

This is an important intermediatecompound called Glyceraldehyde-3-phosphate (a.k.a. PGAL)

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A closer look at the energy investment phase

• Why phosphorylate the sugars first?

– Accomplishes 2 things:

• Traps sugar inside cell (charged phosphate can’t easily go through membrane)

• Makes sugar molecules more reactive (makes them easier to rearrange and split)

Page 35: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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

A closer look at the energy payoff phase2 NAD+

NADH2+ 2 H+

Triose phosphatedehydrogenase

2 P i

2P C

CHOHO

P

O

CH2 O

2 O–

1, 3-Bisphosphoglycerate2 ADP

2 ATP

Phosphoglycerokinase

CH2 O P

2

CCHOH

3-Phosphoglycerate

Phosphoglyceromutase

O–

CC

CH2OH

H O P

2-Phosphoglycerate

2 H2O2 O–

Enolase

CC

OPO

CH2Phosphoenolpyruvate

2 ADP

2 ATPPyruvate kinase

O–

CC

OO

CH3

2

6

8

7

9

10

Pyruvate

O

Figure 9.8 B

Sugar is oxidizedas electrons and H+

are transferred to NAD+, forming NADH (a high energy compound). Very exergonic!

4 ATPs are produced by substrate-level phosphorylation

Net energy gain is 2 ATPs!

Glycolysis produces 2 pyruvate (3C

sugar) molecules –still contain much

energy!

Page 36: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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acetyl CoA• Before the 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

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Formation of acetyl CoA • One carbon is removed (carboxyl group; no

energy left in it), releasing CO2

• Remaining 2-carbon fragment is oxidized to form acetate (ionized form of acetic acid)

• Coenzyme A (sulfur containing; derived from a B vitamin) is attached, forming an unstable molecule with a very reactive acetyl group

• Coenzyme A acts as a shuttle that feeds the 2-carbon acetyl group into the Krebs cycle

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An overview of the citric acid cycle

Glycolysis is linked to Krebs cycle by formation of Acetyl CoA!

ATP

2 CO2

3 NAD+

3 NADH

+ 3 H+

ADP + P i

FAD

FADH2

Citricacidcycle

CoA

CoAAcetyle CoA

NADH+ 3 H+

CoA

CO2

Pyruvate(from glycolysis,2 molecules per glucose)

ATP ATP ATP

Glycolysis Citricacidcycle

Oxidativephosphorylatio

n

Figure 9.11

Page 39: Cellular Respiration: Harvesting Chemical Energynleaders.org/.../Ch-9-cellular-respiration.pdf · Author: Gabriela August Created Date: 11/11/2008 8:18:59 PM

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A closer look at Citric Acid (Krebs) Cycle• The citric acid cycle

– takes place in the matrix of the mitochondrion

– completes the energy-yielding oxidation of organic molecules

– has 8 steps, each catalyzed by a specific enzyme

• Each “turn” of the cycle:

• Releases 2 CO2

• Generates 1 ATP, 3 NADH, and 1 FADH2

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Hans Krebs

(1900-1981)

In case you’re curious . . .

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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–

CHCH2

COO–

HO

COO–

CH

HCCOO–

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 Citric Acid (Krebs) Cycle

Acetyl CoA adds its 2-carbon fragment to a 4-carbon molecule called oxaloacetateto form a 6-carbon molecule called citrate (ionized form of citric acid – gives the cycle its name!)

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A closer look at Citric 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–

CHCH2

COO–

HO

COO–

CH

HCCOO–

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

Carbon dioxide is released

High energy molecules are generated:

3 NADH

1 FADH2

1 ATP

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• It’s called a cycle because at the end of the series of reactions, oxaloacetate is regenerated, allowing the series to repeat as a new acetyl-CoA enters

Another closer look at Citric Acid Cycle

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A closer look at oxidative phosphorylation

• Oxidative phosphorylation

– is ATP synthesis powered by redox reactions that transfer electrons from food to oxygen.

– involves:

• transfer of electrons by NADH and FADH2

• to the electron transport chain

• coupled with chemiosmosis (by which ATP is actually generated)

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A closer look at the Electron Transport Chain• The electron transport chain

• is a collection of molecules embedded in the inner mitochondrial membrane.

• How does this provide an example of STF?

Folding of the inner membrane to form cristae increases its surface area, providing space for thousands of copies of the chain in each mitochondrion.

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A closer look at the Electron Transport Chain

Consists of 5 major components:

• 3 complexes of integral membrane proteins

• 2 freely-diffusible molecules (that shuttle electrons from one complex to the next):

o ubiquinone (a lipid – only member of the ETC that is not a protein!)

o cytochrome c

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A closer look at the Electron Transport 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

Multiproteincomplexes

0

10

20

30

40

50

Free

ene

rgy

(G) r

elat

ive

to O

2 (k

cl/m

ol)

Figure 9.13

Electrons from NADH and FADH2“fall’ through a series of energy releasing steps

3 integral protein complexes

2 “free floating”molecules

At the end of the chain electrons are passed to oxygen, forming water

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Electron Transport Chain – cytochromes

• Cytochromes are key “players” in the ETC!

– are membrane-bound hemoproteins(contain heme groups) that carry out electron transport

– held in membranes in an organized way so redox reactions occur in correct sequence for maximum efficiency!

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A closer look at the Electron Transport Chain

• At certain steps along the electron transport chain electron transfer causes protein complexes to pump H+ from the mitochondrial matrix to the intermembrane space

• The resulting H+ gradient

– Stores energy

– Drives chemiosmosis in ATP synthase

– Is referred to as a proton-motive force

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oxidative phosphorylation = ETC + chemiosmosis

Oxidativephosphorylation.electron transport

and 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 chain (ETC) Chemiosmosis

ATPsynthase

Q

Oxidative phosphorylation!

Intermembranespace

Innermitochondrial

membrane

Mitochondrialmatrix

Figure 9.15

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• Electron transfer in ETC provides energy needed to pump H+ into intermembrane space

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Chemiosmosis

– Chemiosmosis is an energy-coupling mechanism that uses the energy from an H+ gradient generated across a membrane to drive cellular work

– in this case, the cellular work is to make ATP

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Chemiosmosis: The Energy-Coupling Mechanism

• ATP synthase is the enzyme (& molecular motor!) that actually makes ATP

INTERMEMBRANE SPACE

H+

H+

H+

H+

H+

H+ H+

H+

P i+

ADP

ATP

rotor spins clockwise when H+ flows past it down H+ gradient.

stator is anchoredin membrane to hold knobstationary.

rod (“stalk”) extends into knob & also spins, activatingcatalytic sites in knob.

stationary knob contains 3 catalytic sites that join Pi to ADP to make ATP.

MITOCHONDRIAL MATRIX

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Chemiosmosis & ATP synthesis• return flow of H+ turns the molecular motor

(enzyme complex called ATP synthase) which provides energy to make ATP

Motor is driven by

proton motive force!

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Summary of energy flow during cellular respiration

• During respiration, most energy flows in this sequence:

Glucose NADH (FADH2) electron transport chain proton-motive force ATP

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Review of three main metabolic phases

Electron shuttlesspan membraneCYTOSOL 2 NADH

2 FADH2

2 NADH 6 NADH 2 FADH22 NADH

Glycolysis

Glucose2

Pyruvate

2AcetylCoA

Citricacidcycle

Oxidativephosphorylation:electron transport

andchemiosmosis

MITOCHONDRION

substrate-levelphosphorylation

substrate-levelphosphorylation

oxidative phosphorylation (# depends on 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

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Efficiency• About 40% of the energy in a glucose

molecule is transferred to ATP during cellular respiration, making approximately 38 ATP (a car has an efficiency of about 25%)

– Most of this ATP (30-34) is generated by oxidative phosphorylation

– Oxygen is required to harvest the maximum amount of energy from food

Oxygen is the final electron and hydrogen acceptor!

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Glycolysis review

• Glycolysis oxidizes glucose to 2 molecules of pyruvate.

• The oxidizing agent is NAD+, not oxygen!

• Therefore, glycolysis generates 2 ATPs whether oxygen is present (aerobic) or not (anaerobic)

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Fermentation• In the absence of oxygen cells can still

produce ATP through fermentation

• Fermentation is an extension of glycolysisthat can generate ATP solely by substrate-level phosphorylation – as long as there is enough NAD+!

• For this to work, there must be a way to recycle NAD+ from NADH

– NADH must be able to donate its electrons to something!

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Fermentation

• Remember that under aerobic conditions, NADH transfers electrons to the ETC

• Under anaerobic conditions, the only choice is to transfer electrons to pyruvate

• Therefore, fermentation consists of glycolysis plus reactions in which NADH transfers electrons to pyruvate or its derivatives

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Types of Fermentation• Types of fermentation differ in the waste

products formed from pyruvate:

– In alcohol fermentation, pyruvate is converted to ethanol in 2 steps, releasing CO2

• Occurs in yeast and many bacteria

– In lactic acid fermentation, pyruvate is reduced directly to form lactate, with no release of CO2

• Occurs in bacteria, certain fungi, and human muscle cells (sore muscles!)

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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

HH OH

CH3

C

O –

OCC O

CH3

HC O

CH3

O–

C OC O

CH3OC OC OHH

CH3

CO22

Figure 9.17

Types of Fermentation

1 carbon dioxide is removed and released as CO2

NADH reduces acetaldehyde to ethanol

NADH reduces pyruvate to lactate

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Products of Fermentation• Alcohol fermentation:

– Beer, wine

• Lactic acid fermentation:

– Cheese, yogurt

• Combination alcohol & lactic acid fermentation:

– Soy sauce!

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Fermentation vs. Cellular Respiration

• Similarity:

– Both use glycolysis to oxidize glucose and other organic fuels to pyruvate

• Differences:

– final electron acceptor

• Cellular respiration oxygen

• Fermentation pyruvate (or derivative)

– ATP yield

• Cellular respiration about 38 ATP

• Fermentation 2 ATP

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Facultative anaerobes

• Facultative anaerobes are organisms that can use either fermentation or respiration, depending on conditions

– When fermenting, organisms must consume sugar at a faster rate (why?)

– Our muscle cells behave as facultative anaerobes (how?)

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Significance of pyruvate• Pyruvate is the fork in the metabolic road

Glucose

CYTOSOL

PyruvateNo O2 presentFermentation

O2 presentCellular respiration

Ethanolor

lactate

Acetyl CoAMITOCHONDRION

Citricacidcycle

Figure 9.18

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Evolutionary Significance of Glycolysis• Glycolysis

– Occurs in nearly all organisms

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

• Oldest fossils 3.5 billion ya

• Evidence of O2 2.7 billion ya

– Does not require membrane-enclosed organelles, which evolved later

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Catabolic pathways• We get calories (ATP) from various

carbohydrates, fats, and proteins (not just glucose!)

– Glycolysis can accept a wide range of carbohydrates for catabolism

– Amino acids can feed into glycolysis or Krebs cycle after the amino group is removed (deamination) urea/ammonia

– Glycerol (from fats) is converted to PGAL

– Beta oxidation breaks down fatty acids to form acetyl CoA

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Catabolic pathways• The catabolism of various molecules from food

Amino acids

Sugars Glycerol Fattyacids

GlycolysisGlucose

Glyceraldehyde-3- P

Pyruvate

Acetyl CoA

NH3

Citricacidcycle

Oxidativephosphorylation

FatsProteins Carbohydrates

Figure 9.19

Deamination produces nitrogenous wastes

After digestion, food molecules are converted to various intermediate compoundsthat can enter at various stages of respiration

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Anabolic Pathways (Biosynthesis)

• Cells need materials as well as energy! (Not all food molecules are oxidized as fuel to make ATP)

• Instead, intermediates of glycolysis and Krebs cycle can be diverted into anabolic pathways to synthesize needed molecules(this uses ATP!)– Humans can make about half of the 20 amino acids

from Krebs cycle intermediates

– Carbohydrates and proteins can be converted to fats through glycolysis & Krebs cycle intermediates (even fat-free diet can store fat!)

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Feedback Mechanisms in Cellular Respiration

• Cellular respiration is controlled by allosteric enzymes at key points in glycolysis and the citric acid cycle

– Principle of supply & demand

• When cell is working hard, ATP drops, respiration speeds up

• When there is plenty of ATP, respiration slows down

– Phosphofructokinase (allosteric enzyme) is inhibited by ATP and stimulated by AMP

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Control of cellular respiration

• Phosphofructokinase is an important “switch” (regulated by ATP)

Glucose

Glycolysis

Fructose-6-phosphate

Phosphofructokinase

Fructose-1,6-bisphosphateInhibits Inhibits

Pyruvate

ATPAcetyl CoA

Citricacidcycle

Citrate

Oxidativephosphorylation

Stimulates

AMP

+– –

Figure 9.20

Cell doesn’t waste valuable resources!

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One final point . . .

• Remember, the energy that keeps us alive is released, not produced, by cellular respiration!

• That energy was stored in food by photosynthesis (next chapter . . . . ! )

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Any questions?