1. LECTURE PRESENTATIONS
For CAMPBELL BIOLOGY, NINTH EDITION
Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson
Chapter 9
Cellular Respiration and
Fermentation
Lectures by
Erin Barley
Kathleen Fitzpatrick
© 2011 Pearson Education, Inc.

2. Overview: Life Is Work
• Living cells require energy from outside
sources
• Some animals, such as the chimpanzee, obtain
energy by eating plants, and some animals
feed on other organisms that eat plants
© 2011 Pearson Education, Inc.

3. Figure 9.1

4. • Energy flows into an ecosystem as sunlight
and leaves as heat
• Photosynthesis generates O2 and organic
molecules, which are used in cellular
respiration
• Cells use chemical energy stored in organic
molecules to regenerate ATP, which powers
work
© 2011 Pearson Education, Inc.

5. Figure 9.2
Light
energy
ECOSYSTEM
Photosynthesis
in chloroplasts
CO2 + H2O Organic
+ O2
molecules
Cellular respiration
in mitochondria
ATP powers
ATP
most cellular work
Heat
energy

6. Catabolic Pathways and Production of ATP
• The breakdown of organic molecules is
exergonic
• Fermentation is a partial degradation of
sugars that occurs without O2
• Aerobic respiration consumes organic
molecules and O2 and yields ATP
• Anaerobic respiration is similar to aerobic
respiration but consumes compounds other
than O2
© 2011 Pearson Education, Inc.

7. • 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)
© 2011 Pearson Education, Inc.

8. Redox Reactions: Oxidation and Reduction
• The transfer of electrons during chemical
reactions releases energy stored in organic
molecules
• This released energy is ultimately used to
synthesize ATP
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9. The Principle of Redox
• Chemical reactions that transfer electrons
between reactants are called oxidation-reduction
reactions, or redox reactions
• In oxidation, a substance loses electrons, or is
oxidized
• In reduction, a substance gains electrons, or is
reduced (the amount of positive charge is
reduced)
© 2011 Pearson Education, Inc.

10. Figure 9.UN02
becomes oxidized
becomes reduced

11. Oxidation of Organic Fuel Molecules During
Cellular Respiration
• During cellular respiration, the fuel (such as
glucose) is oxidized, and O2 is reduced
© 2011 Pearson Education, Inc.

12. Figure 9.UN03
becomes oxidized
becomes reduced

13. Stepwise Energy Harvest via NAD+ and the
Electron Transport Chain
• In cellular respiration, glucose and other organic
molecules are broken down in a series of steps
• Electrons from organic compounds are usually
first transferred to NAD+, a coenzyme
• As an electron acceptor, NAD+ functions as an
oxidizing agent during cellular respiration
• Each NADH (the reduced form of NAD+)
represents stored energy that is tapped to
synthesize ATP
© 2011 Pearson Education, Inc.

14. Figure 9.4
NAD+ NADH
Dehydrogenase
Reduction of NAD+
(from food) Oxidation of NADH
Nicotinamide Nicotinamide
(oxidized form) (reduced form)

15. • NADH passes the electrons to the electron
transport chain
• Unlike an uncontrolled reaction, the electron
transport chain passes electrons in a series of
steps instead of one explosive reaction
• O2 pulls electrons down the chain in an energy-
yielding tumble
• The energy yielded is used to regenerate ATP
© 2011 Pearson Education, Inc.

16. Figure 9.5
H2 + 1/2 O2 2H + /2 O2
1
(from food via NADH)
Controlled
release of
2H + 2e
+ −
energy for
synthesis of
ATP
Elec chain
ATP
Free energy, G
Free energy, G
tron
Explosive ATP
release of
tran
heat and light ATP
energy
spor
2 e−
t
1
/2 O2
2H +
H2O H2O
(a) Uncontrolled reaction (b) Cellular respiration

17. The Stages of Cellular Respiration:
A Preview
• Harvesting of energy from glucose 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)
© 2011 Pearson Education, Inc.

18. Figure 9.6-3
Electrons Electrons carried
carried via NADH and
via NADH FADH2
Oxidative
Pyruvate
Glycolysis Citric phosphorylation:
oxidation
acid electron transport
Glucose Pyruvate Acetyl CoA cycle and
chemiosmosis
CYTOSOL MITOCHONDRION
ATP ATP ATP
Substrate-level Substrate-level Oxidative
phosphorylation phosphorylation phosphorylation

19. • Oxidative phosphorylation accounts for almost
90% of the ATP generated by cellular
respiration
• A smaller amount of ATP is formed in glycolysis
and the citric acid cycle by substrate-level
phosphorylation
• For each molecule of glucose degraded to CO2
and water by respiration, the cell makes up to
32 molecules of ATP
© 2011 Pearson Education, Inc.

20. Figure 9.7
Enzyme Enzyme
ADP
P
Substrate ATP
Product

21. 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
• Glycolysis occurs whether or not O2 is present
© 2011 Pearson Education, Inc.

22. Figure 9.9-4
Glycolysis: Energy Investment Phase
ATP ATP
Glucose Glucose 6-phosphate Fructose 6-phosphate Fructose 1,6-bisphosphate
ADP ADP
Hexokinase Phosphogluco- Phospho-
isomerase fructokinase
1
2 3
Aldolase 4
Dihydroxyacetone Glyceraldehyde
phosphate 3-phosphate
To
Isomerase 5 step 6

23. Figure 9.9-9
Glycolysis: Energy Payoff Phase
2 ATP 2 ATP
2 NADH 2 H2O
2 ADP
2 NAD+ + 2 H+ 2 ADP 2 2 2
Triose Phospho- Phospho- Enolase Pyruvate
phosphate glyceromutase kinase
2Pi glycerokinase
dehydrogenase 9
1,3-Bisphospho- 7 3-Phospho- 8 2-Phospho- Phosphoenol- 10 Pyruvate
6 glycerate glycerate glycerate pyruvate (PEP)

24. Figure 9.9a
Glycolysis: Energy Investment Phase
ATP
Glucose Glucose 6-phosphate Fructose 6-phosphate
ADP
Hexokinase Phosphogluco-
isomerase
1
2

25. Figure 9.9b
Glycolysis: Energy Investment Phase
ATP
Fructose 6-phosphate Fructose 1,6-bisphosphate
ADP
Phospho-
fructokinase
Aldolase 4
3
Dihydroxyacetone Glyceraldehyde
phosphate 3-phosphate
To
Isomerase 5
step 6

26. Figure 9.9c
Glycolysis: Energy Payoff Phase
2 ATP
2 NADH
2 NAD+ + 2 H+ 2 ADP 2
2
Triose Phospho-
phosphate 2Pi glycerokinase
dehydrogenase
1,3-Bisphospho- 7 3-Phospho-
6 glycerate glycerate

27. Figure 9.9d
Glycolysis: Energy Payoff Phase
2 ATP
2 H2O
2 ADP
2 2 2 2
Phospho- Enolase Pyruvate
glyceromutase kinase
9
3-Phospho- 8 2-Phospho- Phosphoenol- 10 Pyruvate
glycerate glycerate pyruvate (PEP)

28. After pyruvate is oxidized, the citric acid
cycle completes the energy-yielding
oxidation of organic molecules
• In the presence of O2, pyruvate enters the
mitochondrion (in eukaryotic cells) where the
oxidation of glucose is completed
© 2011 Pearson Education, Inc.

29. Oxidation of Pyruvate to Acetyl CoA
• Before the citric acid cycle can begin, pyruvate
must be converted to acetyl Coenzyme A
(acetyl CoA), which links glycolysis to the citric
acid cycle
• This step is carried out by a multienzyme
complex that catalyses three reactions
© 2011 Pearson Education, Inc.

30. Figure 9.10
MITOCHONDRION
CYTOSOL CO2 Coenzyme A
1 3
2
NAD+ NADH + H+ Acetyl CoA
Pyruvate
Transport protein

31. The Citric Acid Cycle
• The citric acid cycle, also called the Krebs
cycle or TCA cycle, completes the break down
of pyrvate to CO2
• The cycle oxidizes organic fuel derived from
pyruvate, generating 1 ATP, 3 NADH, and 1
FADH2 per turn
© 2011 Pearson Education, Inc.

32. Figure 9.11
Pyruvate
CO2
NAD +
CoA
NADH
+ H+ Acetyl CoA
CoA
CoA
Citric
acid
cycle 2 CO2
FADH2 3 NAD+
FAD 3 NADH
+ 3 H+
ADP + P i
ATP

33. • The citric acid cycle has eight steps, each
catalyzed by a specific enzyme
• The acetyl group of acetyl CoA joins the cycle
by combining with oxaloacetate, forming citrate
• The next seven steps decompose the citrate
back to oxaloacetate, making the process a
cycle
• The NADH and FADH2 produced by the cycle
relay electrons extracted from food to the
electron transport chain
© 2011 Pearson Education, Inc.

34. Figure 9.12-8
Acetyl CoA
CoA-SH
NADH
+ H+ 1 H2O
NAD+
8 Oxaloacetate
2
Malate Citrate
Isocitrate
NAD+
Citric 3
NADH
7 acid + H+
H2 O
cycle CO2
Fumarate CoA-SH
α-Ketoglutarate
6 4
CoA-SH
FADH2 5
CO2
NAD+
FAD
Succinate Pi NADH
GTP GDP Succinyl + H+
CoA
ADP
ATP

35. 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
© 2011 Pearson Education, Inc.

36. The Pathway of Electron Transport
• The electron transport chain is in the inner
membrane (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
© 2011 Pearson Education, Inc.

37. Figure 9.13
NADH
50
2 e−
NAD+
FADH2
2 e− FAD Multiprotein
Free energy (G) relative to O2 (kcal/mol)
40 FMN
I complexes
Fe• S II
Fe• S
Q
III
Cyt b
Fe• S
30
Cyt c1
IV
Cyt c
Cyt a
Cyt a3
20
2 e−
10
(originally from
NADH or FADH2)
0 2 H+ + 1/2 O2
H2O

38. • Electrons are transferred from NADH or FADH2
to the electron transport chain
• Electrons are passed through a number of
proteins including cytochromes (each with an
iron atom) to O2
• The electron transport chain generates no ATP
directly
• It breaks the large free-energy drop from food
to O2 into smaller steps that release energy in
manageable amounts
© 2011 Pearson Education, Inc.

39. 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 the proton, 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
© 2011 Pearson Education, Inc.

40. Figure 9.14
INTERMEMBRANE SPACE
A rotor within the
membrane spins as
shown when H+ flows
H+ past it down the H+
Stator
gradient.
Rotor
A stator anchored in
the membrane holds
the knob stationary.
A rod (or “stalk”)
extending into the
knob also spins,
Internal
activating catalytic
rod
sites in the knob.
Catalytic
knob
Three catalytic sites in
the stationary knob
join inorganic
ADP phosphate to ADP to
+ make ATP.
Pi ATP
MITOCHONDRIAL MATRIX

41. Figure 9.15
H+
H +
Protein H +
complex H+
Cyt c
of electron
carriers
IV
Q
III
I
ATP
II synth-
2 H+ + 1/2O2 H2O ase
FADH2 FAD
NADH NAD+
ADP + P i ATP
(carrying electrons
from food) H+
1 Electron transport chain 2 Chemiosmosis
Oxidative phosphorylation

42. • 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
© 2011 Pearson Education, Inc.

43. Proton Motive Force
• Is an electrochemical gradient
• Two gradients drive the protons from the
intermembrane space into the matrix
– It is more negative inside the matrix than in the
intermembrane space, so there is electric potential across
the membrane
• H+ is attracted to the opposite negative charge inside
the matrix
– There is a chemical or pH gradient as well
• Greater concentration of H+ in the intermembrane space
causes the protons to move to an area of lower
concentration inside the matrix
• About 85% of the proton motive force is derived
from the electric or charge gradient while
approximately 15% comes from the chemical
gradient

44. 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 34% of the energy in a glucose molecule
is transferred to ATP during cellular respiration,
making about 32 ATP
© 2011 Pearson Education, Inc.

45. ATP Synthase
• Results from numerous experiments show
that, on average, 3 protons have to pass
through ATP synthase for 1 ATP to be
synthesized
• Therefore, 9 protons would be required to
produce 3 ATP, and we’ve seen that the
electrons from NADH lead to the
translocation of 10 protons into the
intermembrane space
• But, it’s not quite that simple

46. ATP Synthase
• 3 protons produce 1 ATP, but the ATP has to be exported
out of the mitochondria since most of them are used in the
cytoplasm
• Adenine nucleotide translocase exchanges mitochondrial
ATP4- for cytosolic ADP3-, but it results in a -1 net charge
loss in the matrix
• Formation of ATP also requires the import of phosphate
through a phosphate transporter
• Phosphate (H2PO4-) enters with H+ through an
electroneutral symporter
• The cost of moving phosphate and ADP in and ATP out is
approximately equal to the influx of 1 H+
• Thus, synthesis of 1 ATP requires 4 protons

48. P/O Ratio
• Ratio of molecules phosphorylated to atoms of
oxygen reduced
• 2 electrons are required to reduce a single
atom of oxygen
• For each pair of electrons that pass through the
ETC, 10 protons are translocated across the
membrane through ATP synthase
• Since 4 protons are needed for each molecule
of cytoplasmic ATP, the P/O ratio = 10/4 = 2.5
– This applies to NADH, but the electrons involved
in succinate oxidation skip complex I, so 6/4 = 1.5

49. Figure 9.16
Electron shuttles MITOCHONDRION
span membrane 2 NADH
or
2 FADH2
2 NADH 2 NADH 6 NADH 2 FADH2
Glycolysis Pyruvate oxidation Oxidative
Citric phosphorylation:
Glucose 2 Pyruvate 2 Acetyl CoA acid electron transport
cycle and
chemiosmosis
+ 2 ATP + 2 ATP + about 26 or 28 ATP
About
Maximum per glucose: 30 or 32 ATP
CYTOSOL

50. Fermentation and anaerobic
respiration enable cells to produce ATP
without the use of oxygen
• Most cellular respiration requires O2 to produce
ATP
• Without O2, the electron transport chain will
cease to operate
• In that case, glycolysis couples with
fermentation or anaerobic respiration to
produce ATP
© 2011 Pearson Education, Inc.

51. Types of Fermentation
• Fermentation consists of glycolysis plus
reactions that regenerate NAD+, which can be
reused by glycolysis
• Two common types are alcohol fermentation
and lactic acid fermentation
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52. • In alcohol fermentation, pyruvate is converted
to ethanol in two steps, with the first releasing
CO2
• Alcohol fermentation by yeast is used in
brewing, winemaking, and baking
© 2011 Pearson Education, Inc.

53. Figure 9.17
2 ADP + 2 P 2 ATP 2 ADP + 2 P 2 ATP
i i
Glucose Glycolysis Glucose Glycolysis
2 Pyruvate
2 NAD + 2 NADH 2 CO2 2 NAD + 2 NADH
+ 2 H+ + 2 H+
2 Pyruvate
2 Ethanol 2 Acetaldehyde 2 Lactate
(a) Alcohol fermentation (b) Lactic acid fermentation

54. • In lactic acid fermentation, pyruvate is reduced
to NADH, forming lactate as an end product,
with no release of CO2
• Lactic acid fermentation by some fungi and
bacteria is used to make cheese and yogurt
• Human muscle cells use lactic acid
fermentation to generate ATP when O2 is
scarce
© 2011 Pearson Education, Inc.

55. Comparing Fermentation with Anaerobic
and Aerobic Respiration
• All use glycolysis (net ATP =2) to oxidize glucose
and harvest chemical energy of food
• In all three, NAD+ is the oxidizing agent that accepts
electrons during glycolysis
• Cellular respiration produces 32 ATP per glucose
molecule; fermentation produces 2 ATP per
glucose molecule
© 2011 Pearson Education, Inc.

56. • Obligate anaerobes carry out fermentation or
anaerobic respiration and cannot survive in the
presence of O2
• Yeast and many bacteria are facultative
anaerobes, meaning that they can survive
using either fermentation or cellular respiration
• In a facultative anaerobe, pyruvate is a fork in
the metabolic road that leads to two alternative
catabolic routes
© 2011 Pearson Education, Inc.

57. Figure 9.18
Glucose
Glycolysis
CYTOSOL
Pyruvate
No O2 present: O2 present:
Fermentation Aerobic cellular
respiration
MITOCHONDRION
Ethanol, Acetyl CoA
lactate, or
other products
Citric
acid
cycle

58. The Evolutionary Significance of Glycolysis
• Ancient prokaryotes are thought to have used
glycolysis long before there was oxygen in the
atmosphere
• Very little O2 was available in the atmosphere
until about 2.7 billion years ago, so early
prokaryotes likely used only glycolysis to
generate ATP
• Glycolysis is a very ancient process
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59. 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; after
removal of the amino group, the carbon
skeleton can be converted into intermediates of
glycolysis or the citric acid cycle
© 2011 Pearson Education, Inc.

60. • Fats are digested to glycerol (used in
glycolysis) and fatty acids (used in generating
acetyl CoA)
• Fatty acids are broken down by beta oxidation
and yield acetyl CoA
• An oxidized gram of fat produces more than
twice as much ATP as an oxidized gram of
carbohydrate
© 2011 Pearson Education, Inc.

61. Figure 9.19
Proteins Carbohydrates Fats
Amino Sugars Glycerol Fatty
acids acids
Glycolysis
Glucose
Glyceraldehyde 3- P
NH3 Pyruvate
Acetyl CoA
Citric
acid
cycle
Oxidative
phosphorylation

62. Biosynthesis (Anabolic Pathways)
• The body uses small molecules to build other
substances
• These small molecules may come directly
from food, from glycolysis, or from the citric
acid cycle
© 2011 Pearson Education, Inc.

63. Regulation of Cellular Respiration via
Feedback Mechanisms
• Feedback inhibition is the most common
mechanism for control
• If ATP concentration begins to drop,
respiration speeds up; when there is plenty
of ATP, respiration slows down
• Control of catabolism is based mainly on
regulating the activity of enzymes at
strategic points in the catabolic pathway
© 2011 Pearson Education, Inc.

64. Figure 9.20
Glucose
AMP
Glycolysis
Fructose 6-phosphate Stimulates
+
Phosphofructokinase
−
−
Fructose 1,6-bisphosphate
Inhibits Inhibits
Pyruvate
ATP Citrate
Acetyl CoA
Citric
acid
cycle
Oxidative
phosphorylation