Cellular Respiration:

Harvesting Chemical Energy

1
 Cellular Respiration
• All cells can harvest energy from organic
molecules to power work
• To do this, they break down the organic
molecules and use the energy that is released to
make ATP from ADP and phosphate
• There are different catabolic pathways used in
ATP production:
• Fermentation - the partial degradation of sugars
in the absence of oxygen.
• Cellular respiration - A more efficient and
widespread catabolic process that consumes
oxygen as a reactant to complete the breakdown
of a variety of organic molecules.

2
 Catabolic Pathways and Production of ATP
• Although carbohydrates, fats, and proteins are all
consumed as fuel, it is helpful to trace cellular
respiration with the sugar glucose:
• The catabolism of glucose is exergonic with a
G of −686 kcal per mole of glucose.
• Some of this energy is used to produce ATP,
which can perform cellular work

C6H12O6 + 6O2  6CO2 + 6H2O + Energy (ATP + heat)

3
 Redox Reactions
• Catabolic pathways yield energy through the transfer
electrons from one reactant to another by oxidation and
reduction
• Redox reactions
• In oxidation - A substance loses electrons, or is oxidized
• In reduction - A substance gains electrons, or is reduced

becomes oxidized
(loses electron)

Na + Cl Na + + Cl–
becomes reduced
(gains electron)

4
 Oxidation of Organic Fuel Molecules During
Cellular Respiration
• Cellular respiration provides the energy for the cell
using the exergonic reaction:

becomes oxidized

C6H12O6 + 6O2 6CO2 + 6H2O + Energy ~686kcal/mole

becomes reduced

• During cellular respiration glucose is oxidized and

oxygen is reduced
• Glucose oxidation is accomplished in a series of
steps
5
 Glucose Oxidation
• 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

Figure 9.5 A H2O

6
 Glucose Catabolism
• Glucose catabolism is a series of redox reactions that release energy
by repositioning electrons closer to oxygen atoms.
• The high energy electrons are stripped from glucose and picked up by
NAD+ and FAD.

2 e– + 2 H+
2 e– + H+
NAD+ NADH
H
O Dehydrogenase
H H O
NH2 + 2[H] Reduction of NAD+ NH2 + H
C C
(from food) Oxidation of NADH
N+ N Nicotinamide
Nicotinamide
O CH2 (oxidized form) (reduced form)
O
O P O –

O H H
O P O– HO OH NH2
HO
CH2
O N N
H
N N H
O

H H
HO OH Figure 9.4
7
 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
• Eventually, the electrons, along with H+, are passed to a final acceptor.

2H + 1
/2 O2
NADH
(from food via NADH) 50

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

FADH2
Controlled
release of Multiprotein
2 H+ + 2 e– 40 I FAD complexes
energy for FMN
synthesis of Fe•S Fe•S II
ATP Q
III
ATP Cyt b
Fe•S
Free energy, G

30
ATP Cyt c1 IV
Cyt c
Cyt a
ATP Cyt a3
20

10

2 e–
1
/ 2 O2
2 H+ 2 H+ + 1/2 O2
0

H2O 8H O
2
 Glucose Catabolism
• If molecular oxygen (O2) is the final electron
acceptor, the process is called aerobic
respiration.
• If some other inorganic molecule is the final
electron acceptor, the process is called
anaerobic respiration.
• If an organic molecule is the final electron
acceptor, the process is called fermentation.

9
 The Stages of Cellular Respiration
• Respiration is a cumulative function of three
metabolic stages
• Glycolysis - breaks down glucose into two
molecules of pyruvate
• The Citric Acid Cycle (Kreb’s) - completes the
breakdown of glucose
• Oxidative phosphorylation - driven by the
electron transport chain and Generates ATP

10
 Cellular Respiration

Electrons Electrons carried

carried via NADH and
via NADH FADH2

Oxidative
Citric phosphorylation:
Glycolsis
Glucos acid electron
Pyruvate cycle
e transport and
chemiosmosis

Cytosol
Mitochondrion

ATP ATP ATP

Substrate-level Oxidative
Substrate-level
phosphorylation phosphorylation
phosphorylation

11
 Substrate Phosphorylation
• Both glycolysis and the citric acid cycle can
generate ATP by substrate-level phosphorylation
Enzyme Enzyme

Substrate ADP

P
Product + ATP

PEP uv ate
r
Py
P
P
P AT
P P
Enzyme ADP
P P
osine
Adenosine n
Ade 12
 Glycolysis

• 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

13
 Glycolysis
• Occurs in the cytoplasm of
the cell
• Results in the partial
breakdown of glucose
• Anaerobic – no oxygen is
used during glycolysis
• For each molecule of
glucose that passes
through glycolysis, the cell
nets two ATP molecules.
Glycolysis Citric
acid Oxidative
cycle phosphorylation

ATP ATP ATP

14
Glycolysis
Glycolysis Citric
Oxidation
acid
cycle phosphorylation

ATP ATP ATP

Glucose

ATP
• Energy investment phase Hexokinase
ADP

ATP/NADH Ledger

- 1 ATP Glucose-6-phosphate

15
Glycolysis
Glycolysis Citric
Oxidation
acid
cycle phosphorylation

ATP ATP ATP

Glucose

ATP
• Total of 2 ATP invested Hexokinase
ADP

ATP/NADH Ledger

- 2 ATP Glucose-6-phosphate

Phosphoglucoisomerase

Fructose-6-phosphate

ATP

Phosphofructokinase
ADP

Fructose-
1, 6-bisphosphate

Aldolase

Isomerase

Dihydroxyacetone Glyceraldehyde-
phosphate 3-phosphate 16
 NAD+ NAD+

Glycolysis
Triose phosphate Triose phosphate
dehydrogenase dehydrogenase
NADH NADH
+ H+ + H+

• Energy payoff 1, 3-Bisphosphoglycerate 1, 3-Bisphosphoglycerate

phase
ADP ADP

Phosphoglycerokinase Phosphoglycerokinase
ATP ATP

ATP/NADH Ledger

- 2 ATP 3-Phosphoglycerate 3-Phosphoglycerate

+ 2 ATP
Phosphoglyceromutase Phosphoglyceromutase
+ 2 NADH

2-Phosphoglycerate 2-Phosphoglycerate

17
 NAD+ NAD+

Glycolysis
Triose phosphate Triose phosphate
dehydrogenase dehydrogenase
NADH NADH
+ H+ + H+

• End-products of 1, 3-Bisphosphoglycerate 1, 3-Bisphosphoglycerate

glycolysis are 2 ADP ADP

pyruvate molecules Phosphoglycerokinase Phosphoglycerokinase

ATP ATP

ATP/NADH Ledger
3-Phosphoglycerate 3-Phosphoglycerate
- 2 ATP
+ 4 ATP Phosphoglyceromutase Phosphoglyceromutase

+ 2 NADH

2-Phosphoglycerate 2-Phosphoglycerate

Enolase Enolase
H2O H2O

Phosphoenolpyruvate Phosphoenolpyruvate
ADP ADP

Pyruvate kinase Pyruvate kinase

ATP ATP

18
Pyruvate Pyruvate
 Glycolysis Summary
• Occurs in the cytoplasm
Energy investment phase
• Glucose converted to two
3-C chains Glucose
• Anaerobic - no oxygen
• 2 ATP used, 4 ATP 2 ADP + 2 P 2 ATP used
produced
• Inefficient - net yield only 2
ATPs Energy payoff phase
• Not discarded by evolution 4 ADP + 4 P 4 ATP formed
but used as starting point
for energy production
• If no O2 - Fermentation 2 NAD+ + 4 e– + 4 H+ 2 NADH + 2 H+

occurs
• End products: 2 Pyruvate + 2 H2O
• 2 ATP
Net
• Pyruvate (3 C) Glucose 2 Pyruvate + 2 H2O
• 2 x CO2
4 ATP formed – 2 ATP used 2 ATP
• 2 x NADH
2 NAD+ + 4 e– + 4 H+ 2 NADH + 2 H+
19
 The Citric Acid (Krebs) Cycle
The Krebs cycle is named after Hans Krebs and is a metabolic event
that follows glycolysis. This process occurs in the fluid matrix of the
mitochondrion, uses the pyruvic acid from glycolysis and is aerobic. To
begin the Krebs cycle, pyruvic acid is converted to acetyl CoA.

20
 Oxidation of Pyruvate
• More energy can be extracted if oxygen is present
• Within mitochondria, pyruvate is decarboxylated,
yielding acetyl-CoA, NADH, and CO2

CYTOSOL MITOCHONDRION

NAD+ NADH + H+

Acetyl Co A
Pyruvate CO2 Coenzyme A

Transport protein
21
 The Citric Acid (Krebs) Cycle

• Occurs in the
mitochondrial matrix
• Aerobic – although O2 is
not used directly in this
pathway, it will not occur
unless enough is present
in the cell.
• Main catabolic pathway
• Acetyl-CoA is oxidized in a
series of nine reactions

22
Krebs Cycle Glycolysis Citric
acid
cycle
Oxidation
phosphorylation

ATP ATP ATP

• AcetylCoA reacts with

oxaloacetate using an Acetyl CoA

enzyme called citrate

synthase producing H2O

citric acid.
Oxaloacetate

• Because of this, the Citrate

Isocitrate

Krebs cycle is Citric

acid
sometimes called the cycle

citric acid cycle.

23
Krebs Cycle Glycolysis Citric
acid
cycle
Oxidation
phosphorylation

• The next 7 steps ATP ATP ATP

decompose the
citrate back to Acetyl CoA

oxaloacetate,
• Citric acid is H 2O

systematically Oxaloacetate

decarboxylated and Citrate

dehyrogenated in Isocitrate

order to use up the Citric

acid
CO2

acetyl groups that cycle NAD+

were attached to the

NADH
Fumarate + H+

oxaloacetate. a-Ketoglutarate

• This allows
oxaloacetate and
FADH2
CO2
NAD+
FAD

CoA to be used in Succinate

Pi
Succinyl
NADH
+ H+

the next cycle.

GTP GDP
CoA

ADP

ATP

24
Krebs Cycle Glycolysis Citric
acid
cycle
Oxidation
phosphorylation

ATP ATP ATP

• The NADH and

FADH2 produced Acetyl CoA

by the cycle relay NADH

H2 O
+ H+

electrons extracted NAD +

Oxaloacetate

from food to the Malate Citrate

electron transport Citric

Isocitrate

CO2

chain H2O
acid
cycle NAD+

NADH
Fumarate + H+

ATP/NADH Ledger a-Ketoglutarate

+ 2 ATP FADH2
CO2
NAD+
+ 6 NADH FAD
Succinate
+ 2 FADH2 Pi
Succinyl
NADH
+ H+
GTP GDP
CoA

ADP

ATP

25
Krebs Cycle

26
 ETC and Oxidative Phosphorylation
• Occurs along the inner mitochondrial membrane (IMM) in the
cristae of the mitochondrion
• NADH/FADH2 molecules carry electrons from glycolysis and the
citric acid cycle to the inner mitochondrial membrane, where they
transfer electrons to a series of membrane-associated proteins.

27
 The Pathway of Electron Transport
• Most of the chain’s
components are proteins,
NADH
50

which exist in multiprotein FADH2

complexes 40 FMN
I FAD
Multiprotein
complexes

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

Fe•S II
• The carriers alternate Fe•S
Q
III

reduced and oxidized 30

Cyt b
Fe•S

states as they accept and Cyt c1

Cyt c
IV

donate electrons 20
Cyt a
Cyt a3

• Electrons drop in free

energy as they go down 10

the chain and are finally

passed to O2, forming 0 2 H+ + 1/2 O2

water
28
H2O
 The Pathway of Electron Transport
• The electron transport NADH

chain generates no 50

ATP FADH2

Multiprotein
I complexes
• The chain’s function is 40 FMN FAD

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

Fe•S Fe•S II
Q

to break the large free- 30

Cyt b
Fe•S
III

energy drop from food Cyt c1

Cyt c
IV

to O2 into smaller steps

Cyt a
Cyt a3
20

that release energy in

manageable amounts 10

0 2 H+ + 1/2 O2

29
H2O
 Electron Transport Phosphorylation
• Electron transfer in the electron transport chain causes proteins to pump H+
from the mitochondrial matrix to the intermembrane space
• The ETC uses energy from electrons to pump H+ across a membrane against
their concentration gradient - potential energy.
• H+ then moves back across the membrane, passing through channels in 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

30
 LE 9-15

Inner
mitochondrial
membrane

Oxidative
Glycolysis Citric
acid phosphorylation:
cycle electron transport
and chemiosmosis

ATP ATP ATP

H+
H+

H+
H+
Protein complex Cyt c
Intermembrane of electron
space carriers

Q IV

I III
ATP
II synthase
Inner
2H+ + 1/2 O2 H2O
mitochondrial FADH2 FAD
membrane
NADH + H+ NAD+
ADP + P i ATP
(carrying electrons
from food)
H+

Mitochondrial Electron transport chain Chemiosmosis

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

31
 ATP
• The energy stored in a H+ gradient Intermembrane
across a membrane couples the redox space H+
H+
H+ H+
reactions of the electron transport chain
to ATP synthesis H+
H+
H+
H+
• The H+ gradient is referred to as a
proton-motive force, emphasizing its Rotor
capacity to do work

• Most of the ATP produced in cells is

made by the enzyme ATP synthase
Rod
• The enzyme is embedded in the
membrane and provides a channel Catalytic
through which protons can cross the head
membrane down their concentration
gradient ADP + Pi

• The energy released causes the rotor ATP

and the rod structures to rotate. This
H+
mechanical energy is converted to
chemical energy with the formation of Mitochondrial matrix
ATP
32
LE 9-14

INTERMEMBRANE SPACE
H+ A rotor within the
membrane spins
H+ H+
as shown when
H+ flows past
H+
H+ it down the H+
gradient.
H+
H +

A stator anchored
in the membrane
holds the knob
stationary.

A rod (or “stalk”)

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

Three catalytic
sites in the
ADP stationary knob
+ join inorganic
ATP phosphate to
P
i ADP to make
ATP.
MITOCHONDRAL MATRIX

33
Summary
of Glucose
Catabolism

34
Theoretical ATP Yield of Aerobic
Respiration

35
 Catabolism of Proteins and Fats
• Proteins are utilized by deaminating their amino acids, and
then metabolizing the product.
• Fats are utilized by beta-oxidation.

36
 Regulating Aerobic Respiration
• Control of glucose catabolism occurs at two key points in the catabolic
pathway.
• Glycolysis - phosphofructokinase
• Pyruvate Oxidation – pyruvate decarboxylase

37
 Recycling NADH
• As long as food molecules are available to
be converted into glucose, a cell can
produce ATP.
• Continual production creates NADH
accumulation and NAD+ depletion.
• NADH must be recycled into NAD+.
• Aerobic respiration - oxygen as electron
acceptor
• Fermentation - organic molecule

38
 Lactic Acid Fermentation
• Used by most animal cells when O2 is not available
• NADH donates 2 e- and a H+ directly to the pyruvate (3C)
produced during glycolysis, producing lactate (3C) and
NAD+

2 ADP + 2 P i 2 ATP

Glucose O–
G
Glycolysis C O
Glucose
2 ADP L H C OH
Y CH3
2 ATP C 2 Lactate
O 2 NAD+
2 NAD+ 2 NADH 2 CO2
L
+2H +

- Y 2 NADH 2 Pyruvate
O S
C O
I
C O S
CH3 2 Pyruvate
2 Lactate
39
Lactic acid fermentation