CHAPTER 9:

CELLULAR RESPIRATION
 Overview: Life Is Work
• Living cells
– Require transfusions of energy from outside sources
to perform their many tasks
• The giant panda
– Obtains energy for its cells by eating plants
• Energy
– Flows into an ecosystem as sunlight and leaves as heat; the
chemical elements essential to life are recycled

Light energy

ECOSYSTEM

Photosynthesis
How cells harvest the
in chloroplasts Organic chemical energy stored in
CO2 + H2O + O2
Cellular molecules organic molecules & use it
respiration
in mitochondria to generate ATP, the
molecule that drives most
cellular work?

ATP
powers most cellular work

Heat
energ
y
 Catabolic pathways yield energy by oxidizing
organic fuels

Catabolic Pathways and Production of ATP

• Metabolic pathways that release stored energy by

breaking down complex molecules  catabolic pathways
• The breakdown of organic molecules is exergonic

• Fermentation (catabolic process)

– Is a partial degradation of sugars that occurs without
the use of oxygen
• Cellular respiration
– Is the most prevalent and efficient catabolic pathway
– Consumes oxygen and organic molecules such as
glucose
– Yields ATP

• Catabolism is linked to work by a chemical drive shaft -

ATP
• To keep working
– Cells must regenerate its supply of ATP from ADP
and Pi (Inorganic phosphate)
 Redox Reactions: Oxidation and Reduction

• Catabolic pathways yield energy

– Due to the transfer of electrons during the chemical
reactions

• The relocation of electrons releases energy stored in

organic molecules
– And this energy ultimately is used to synthesize ATP
by using enzyme.
The Principle of Redox

• Redox reactions
– Transfer electrons from one reactant to another by
oxidation and reduction
• In oxidation
– A substance loses electrons, or is oxidized
• In reduction
– A substance gains electrons, or is reduced
• Examples of redox reactions
becomes oxidized
(loses electron)

Na + Cl Na+ + Cl–
becomes reduced
(gains electron)
 • Some redox reactions
– Do not completely exchange electrons
– Change the degree of electron sharing in covalent bonds

Reactants Products Energy must be added to pull an e-

becomes oxidized away from an atom.

CH4 + 2O2
CO
+
Energ
+ 2 H2O The more electronegative the atom
y
2
(the stronger its pull on e-), the more
becomes
H
reduced energy is required to take away an e-.
H
C
H
O O O C O
H
O
H An e- loses potential energy when it
shifts from a less electronegative
atom to a more electronegative one.
H

Methane Oxygen Carbon dioxide Water

(reducing (oxidizing A redox reaction that relocates e-
agent) agent)
closer to O2 (eg. burning of methane),
releases chemical energy that can be
Methane combustion as an energy-yielding
redox reaction used for work.
 Oxidation of Organic Fuel Molecules During Cellular
Respiration

• During cellular respiration

– Glucose is oxidized and oxygen is reduced. Why?

becomes oxidized
C6H12 O6 + 6O2 6CO2 + 6H2O + Energy

becomes reduced

• The electrons lose potential energy along the way;

energy is released.
 Stepwise Energy Harvest via NAD+ and the Electron
Transport Chain
• Cellular respiration
– Oxidizes glucose in a series of steps, each step
catalyzed by an enzyme.
• At key steps, e- are stripped from the glucose, each
electron travels with a proton (H atom)

• H atom from organic compounds are not transferred

directly to oxygen
– But are usually first transferred to NAD+, a coenzyme
• As an electron acceptor, NAD+ functions as an oxidizing
agent during respiration
 2 e– + 2 H +
2 e– + H +
NAD +
NADH H+
H
O Dehydrogenase
H H O
NH2 + 2[H] Reduction of NAD+ NH2 +
C C H+
(from food) Oxidation of NADH
N+ N Nicotinamide
Nicotinamide
O CH2 (oxidized form) (reduced form)
O
O P O –

O H H
NAD+ as an electron shuttle.
O P O– HO OH NH2
CH2HO The enzymatic transfer of two electrons and
O N N
H one proton (H+) from an organic molecule in
N N H
O food to NAD+ reduces the NAD+ to NADH;
the second proton (H+) is released.
H H
HO OH
• Most of the electrons removed from food are transferred
initially to NAD+
• NADH, the reduced form of NAD+
– 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
H2 + 1/2 O2

Free energy, G

Explosive
release of (a) Uncontrolled reaction
heat and light
energy

H2O
• The electron transport chain
2H + 1
/2 O2
– Passes electrons in a
series of steps instead of (from food via NADH)

in one explosive reaction Controlled

release of
– Uses the energy from the 2 H+ + 2 e–
energy for
electron transfer to form synthesis of

Elec
ATP
ATP
ATP

Free energy, G

tr
on tr
ATP
e- removed from food are shuttled by

ansp
NADH to the ‘top’, higher-energy end ATP
of the chain

ort c
At the ‘bottom’, lower-energy end,

ain h
oxygen captures these e- along with 2 e–
H+, forming water. 1
/ 2 O2
2H +

In cellular respiration, e- travel this

‘downhill’ route H2O

Food  NADH  Electron Transport

Chain  oxygen (b) Cellular respiration
 The Stages of Cellular Respiration: A Preview

• Respiration is a cumulative function of three metabolic

stages
– Glycolysis: Breaks down glucose into two molecules of
pyruvate
– The citric acid cycle: Completes the breakdown of glucose
– Oxidative phosphorylation (electron transport &
chemiosmosis): Is driven by the electron transport chain ,
Generates ATP
 An overview of cellular respiration

Glycolysis occurs in This mode of ATP synthesis is called oxidative

the cytosol. phosphorylation because it is powered by the redox
reactions of the ETC. In the third stage of
Begins degradation
Electr respiration, the ETC
by breaking glucose ons
accepts e- from the 1st
into 2 molecules of carrie Electrons carried
d via NADH and two stages breakdown
pyruvate via FADH2
NAD
Ci products via NADH &
H Oxidative
tri
phosphor passes these e- from 1
The citric acid cycle c
Glycolysis ac
ylation: molecule to another.
takes place within Glu
Pyruvate id
electron
cos transport
the mitochondrial e cy and At the end of the chain,
cl e- are combined with
matrix. e
chemios
mosis
Cytosol Mitochondrion molecular O2 and H+ to
Completes the
form water.
breakdown of
glucose by oxidizing ATP ATP ATP The energy released at
a derivative of Substrate-level Oxidative each step of the chain is
Substrate-level
pyruvate to CO2 phosphorylation phosphorylationphosphorylation stored in a form the
mitochondrion can use
to make ATP.
• Both glycolysis and the citric acid cycle
– Can generate ATP by substrate-level phosphorylation

Enzyme Enzyme

ADP

P
Substrate
+ ATP

Product

Substrate level phosphorylation

Some ATP is made by direct enzymatic transfer of a phosphate group from an
organic substrate to ADP.

In oxidative phosphorylation, an inorganic phosphate is added

to ADP.
 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 Citric Oxidative
acid
phosphorylation
•
cycle
Glycolysis consists of
two major phases
ATP ATP ATP
– Energy investment
Energy investment phase
phase
Glucose
– Energy payoff
phase 2 ATP + 2 P 2 ATP used

Energy payoff phase

4 ADP + 4 P 4 ATP formed

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

2 Pyruvate + 2 H2O

Net
Glucose 2 Pyruvate + 2 H2O
4 ATP formed – 2 ATP used 2 ATP + 2 H+

2 NAD+ + 4 e– + 4 H + 2 NADH
A closer look at the energy investment phase
CH2OH
Citric
HH H Glycolysis acid Oxidative
HO H cycle phosphorylation
HO OH
H OH
Glucose

ATP 1

Hexokinase
1 Glucose is phosphorylated by hexokinase.
ADP
Hexokinase transfers a P group from ATP to
CH2OH P
H O H the sugar.
H
OH H
HO
H OH
Glucose-6-phosphate
2 2 Glucose-6-phosphate is rearranged to its
Phosphoglucoisomerase isomer, fructose-6-phosphate
CH2O P
O CH2OH
H HO
H HO
HO H
Fructose-6-phosphate 3 Enzyme transfers a P group from ATP to
3 the sugar.
ATP
Phosphofructokinase
P groups on opposite sides, sugar is ready
ADP
to be split in half.
P O CH2 O CH2 O P
HO
H
HO H
OH 4 Enzyme cleaves the sugar molecule into
Fructose-
1, 6-bisphosphate
two different 3-carbon sugars (isomers)
4
Aldolase

P
5
O CH2 Isomerase
H 5 Net result of steps 4 and 5 is cleavage of
C O
C O a 6-carbon sugar into two molecules of
CHOH
CH2OH
CH2 O P
glyceraldehyde-3-phosphate.
Dihydroxyacetone Glyceraldehyde-
phosphate 3-phosphate
A closer look at the energy payoff phase

2 NAD+
6
Triose phosphate
6 Sugar is oxidized by transfer of electrons
dehydrogenase and H+ to NAD+, forming NADH (exergonic).
2 NADH 2 Pi
+ 2 H+ Enzyme uses this energy to attach a P group to
2
P O C O the oxidized substrate.
CHOH
CH2 O P
1, 3-Bisphosphoglycerate
2 ADP
7 7 Phosphate group is transferred to ADP to
Phosphoglycerokinase
produce ATP.
2 ATP

2 O–

C
CHOH
CH2 O P 8 Enzyme relocates the P group.
3-Phosphoglycerate
8
Phosphoglyceromutase

2 O–

C O
H C O P
CH2OH
2-Phosphoglycerate
9 Enolase causes a double bond to form in the
9 substrate, extracting a water molecule, yielding
2 H2O
O–
Enolase
PEP.
2
C O
C O P
CH2

2 ADP
Phosphoenolpyruvate 10 Pyruvate kinase transfers P group from PEP
10
Pyruvate kinase
to ADP.
2 ATP

2 O– Net gain of 2 ATP (2 ATP used, 4 ATP

C
C O
O
produced)
CH3
Pyruvate
 The citric acid cycle completes the energy-yielding
oxidation of organic molecules

• Less than a ¼ of chemical energy in glucose is released in

glycolysis; most energy is stockpiled in 2 molecules of
pyruvate
• The citric acid cycle
– Takes place in the matrix of the mitochondrion

• If molecular O2 is present, pyruvate enters mitochondrion;

enzymes of the citric acid cycle complete the oxidation of
the organic fuel.
 • Before the citric acid cycle can begin
– Pyruvate must first be converted to acetyl CoA, which links the cycle
to glycolysis
2 The remaining 2C fragment is
oxidized to acetate. 3 Coenzyme A (sulfur-
containing compound derived
An enzyme transfers the extracted
from a B vitamin) is attached to
electrons to NAD+, storing energy in the acetate by an unstable bond.
the form of NADH.
1 Pyruvate’s CYTOSOL MITOCHONDRION

carboxyl group This acetyl

(-COO-) which is fully group, very
oxidized and has little reactive.
NAD +
NAD+
chemical energy, is H H+
Acetyl CoA is
O– Co
released as CO2. S
A now ready to
2
C O feed its acetyl
C O group into the
C O citric acid
CH3 cycle for
1 3
CH3 Acetyle further
Coenzyme
CoA oxidation.
Pyruvate CO2
A

Transport protein
 An overview of the citric acid cycle

Pyruvate Glycolysis Citric

Oxidative
acid
(from glycolysis, cycle phosphorylation

2 molecules per glucose)

ATP ATP ATP

CO2 The cycle generates 1 ATP per turn by

CoA substrate-level phosphorylation, but
NADH most of the chemical energy is
+ 3 H+ Acetyle CoA transferred to NAD+ and the related
CoA coenzyme FAD during redox
CoA
reactions.

Citric The reduced coenzymes, NADH and

acid 2 CO2
FADH2, shuttle their high-energy
cycle electrons to the ETC.
FADH2 3 NAD+

FAD 3 NADH
+ 3 H+
ADP + P i
ATP
Summary of the inputs and outputs as pyruvate is broken
down to 3 CO2 molecules, including the molecule of CO2
released
A closer look at the citric acid cycle

Citric Oxidative
Glycolysis
acid phosphorylation
cycle

S CoA
C O
CH3
Acetyl CoA
CoA SH

NADH O C COO–
+ H+ CH2 1 COO– H2O
COO – CH2 COO–
NAD +

8 Oxaloacetate HO C COO–
CH2
CH2 2
COO – HC COO–
COO– HO CH
HO CH
Malate Citrate
CH2 Figure 9.12 COO–
Isocitrate
COO–
CO2
Citric
3
7 acid NAD+
H2 O cycle
COO–
COO– NADH
CH + H+
Fumarate CoA SH CH2
HC
CH2 α -Ketoglutarate
COO–
C O
6 4
COO– CoA SH COO– COO–

CH2 CH2
FADH2 5
CH2 CH2 CO2
FAD NAD+
COO– C O
Succinate Pi S CoA NADH
GTP GDP Succinyl + H+
CoA
ADP

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

• NADH and FADH2

– Donate electrons to the electron transport chain, which
powers ATP synthesis via oxidative phosphorylation
 The Pathway of Electron Transport

• In the electron transport chain

– Electrons from NADH and FADH2 lose energy in
several steps
• At the end of the chain
– Electrons are passed to
oxygen, forming water
NADH
50

FADH2

I Multiprotein
40 FMN FAD complexes
II

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

Fe•S Fe•S

O
III
Cyt b

30 Fe•S
Cyt c1

Cyt c IV

Cyt a
Cyt a3
20

10

0 2 H + + 1⁄ O2
2

H2O
 Chemiosmosis: The Energy-Coupling Mechanism
INTERMEMBRANE SPACE
A rotor within the
• ATP synthase H+ H+
H+
membrane spins
clockwise when
– Is the enzyme that H+ H+ flows past
H+
actually makes ATP it down the H+
gradient.
H+
H+
A stator anchored
in the membrane
holds the knob
stationary.

A rod (for “stalk”)

extending into
the knob also
spins, activating
catalytic sites in
H+ the knob.

Three catalytic
sites in the
ADP
stationary knob
+ join inorganic
Pi ATP
Phosphate to ADP
to make ATP.
MITOCHONDRIAL MATRIX
• 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
• Chemiosmosis
– Is an energy-coupling mechanism that uses energy in
the form of a H+ gradient across a membrane to drive
cellular work
 Chemiosmosis and the electron transport chain

Inner
Mitochondrial
Glycolysis
Oxidative
phosphorylation. membrane
electron transport
and chemiosmosis

ATP ATP ATP

H+
H +

H+
H+
Cyt c
Protein complex
Intermembrane of electron
space carners
Q IV
I III
ATP
Inner II synthase
mitochondrial FADH2 H2O
membrane FAD+ 2 H+ + 1 /2 O2
NADH+
NAD+ ADP + Pi ATP
(Carrying electrons
from, food) H+
Mitochondrial Chemiosmosis
Electron transport chain
matrix Electron transport and pumping of protons (H ), ATP synthesis powered by the flow
+

which create an H+ gradient across the membrane Of H+ back across the membrane
Oxidative phosphorylation
 An Accounting of ATP Production by Cellular
Respiration

• During respiration, most energy flows in this sequence

– Glucose to NADH to electron transport chain to proton-
motive force to ATP

• There are three main processes in this metabolic

enterprise
 Electron shuttles MITOCHONDRION
CYTOSOL 2 NADH
span membrane
or
2 FADH2

2 NADH 2 NADH 6 NADH 2 FADH2

Glycolysis Oxidative
2 Citric phosphorylation:
2 Acetyl acid electron transport
Glucose Pyruvate CoA cycle and
chemiosmosis

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

by substrate-level by substrate-level by oxidative phosphorylation, depending
phosphorylation phosphorylation on which shuttle transports electrons
from NADH in cytosol

About
Maximum per glucose: 36 or 38 ATP
• 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
– Cells can still produce ATP through fermentation
• Glycolysis
– Can produce ATP with or without oxygen, in aerobic
or anaerobic conditions
– Couples with fermentation to produce ATP
 Types of Fermentation

• Fermentation consists of
– Glycolysis plus reactions that regenerate NAD+, which
can be reused by glyocolysis
• In alcohol fermentation
– Pyruvate is converted to ethanol in two steps, one of
which releases CO2

• During lactic acid fermentation

– Pyruvate is reduced directly to NADH to form lactate
as a waste product
 2 ADP + 2 P1 2 ATP O–
C O
C O
Glucose Glycolysis
CH3

2 Pyruvate

2 NAD+ 2 NADH 2 CO2

H H
H C OH C O
CH3 CH3
2 Ethanol 2 Acetaldehyde
(a) Alcohol fermentation

2 ADP + 2 P1 2 ATP

Glucose Glycolysis O–
C O
C O
2 NAD + 2 NADH
O CH3

C O
H C OH
CH3
2 Lactate
(b) Lactic acid fermentation
 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
– Differ in their final electron acceptor
• Cellular respiration
– Produces more ATP
• Pyruvate is a key juncture in catabolism
Glucose

CYTOSOL

Pyruvate
No O2 present O2 present
Fermentation Cellular respiration

MITOCHONDRION
Ethanol Acetyl CoA
or
lactate
Citric
acid
cycle
 The Evolutionary Significance of Glycolysis

• Glycolysis
– Occurs in nearly all organisms
– Probably evolved in ancient prokaryotes before there
was oxygen in the atmosphere
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

 Proteins Carbohydrates Fats

Amino Sugars Glycerol Fatty

acids 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 or through glycolysis or the
citric acid cycle
 Regulation of Cellular Respiration via Feedback
Mechanisms

• Cellular respiration
– Is controlled by allosteric enzymes at key points in
glycolysis and the citric acid cycle
• The control of cellular respiration

Glucose

AMP
Glycolysis

Fructose-6-phosphate Stimulates
+
Phosphofructokinase
– –
Fructose-1,6-bisphosphate
Inhibits Inhibits

Pyruvate

ATP Citrate
Acetyl CoA

Citric
acid
cycle

Oxidative
phosphorylation