(a) The structure of ATP

Phosphate groups
Adenine
Ribose
Adenosine triphosphate (ATP)
Energy
Inorganic
phosphate
Adenosine diphosphate (ADP)
(b) The hydrolysis of ATP
The Structure
and Hydrolysis
of ATP
ATP drives
endergonic reactions
by phosphorylation,
transferring a
phosphate group to
some other molecule,
such as a reactant
The recipient
molecule is now
called a
phosphorylated
intermediate
How the Hydrolysis of ATP Performs Work
The bonds between the phosphate groups of ATPs tail can
be broken by hydrolysis
Energy is released from ATP when the terminal phosphate
bond is broken
This release of energy comes from the chemical change to
a state of lower free energy, not from the phosphate bonds
themselves
The three types of cellular work (mechanical, transport, and
chemical) are powered by the hydrolysis of ATP
In the cell, the energy from the exergonic reaction of ATP
hydrolysis can be used to drive an endergonic reaction
Overall, the coupled reactions are exergonic
The Regeneration of ATP
ATP is a renewable resource that is regenerated by addition of a
phosphate group to adenosine diphosphate (ADP)
The energy to phosphorylate ADP comes from catabolic reactions in
the cell
The ATP cycle is a revolving door through which energy passes
during its transfer from catabolic to anabolic pathways
Energy from
catabolism (exergonic,
energy-releasing
processes)
Energy for cellular
work (endergonic,
energy-consuming
processes)
ATP
ADP P
i

H
2
O
Enzymes speed up metabolic reactions by
lowering energy barriers
A catalyst is a chemical agent that speeds up a
reaction without being consumed by the reaction
An enzyme is a catalytic protein
Hydrolysis of sucrose by the enzyme sucrase is an
example of an enzyme-catalyzed reaction
Sucrase
Sucrose
(C
12
H
22
O
11
)
Glucose
(C
6
H
12
O
6
)
Fructose
(C
6
H
12
O
6
)
Figure 8.13
Course of
reaction
without
enzyme
E
A

without
enzyme
E
A
with
enzyme
is lower
Course of
reaction
with enzyme
Reactants
Products
!G is unaffected
by enzyme
Progress of the reaction
F
r
e
e

e
n
e
r
g
y

Oxidation of Organic Fuel Molecules During
Cellular Respiration
During cellular respiration, the fuel (such as glucose)
is oxidized, and O
2
is reduced
becomes oxidized
becomes reduced
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
Dehydrogenase
Nicotinamide
(oxidized form)
NAD
+

(from food)
Dehydrogenase
Reduction of NAD
+

Oxidation of NADH
Nicotinamide
(reduced form)
NADH
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
O
2
pulls electrons down the chain in an
energy-yielding tumble
The energy yielded is used to
regenerate ATP
(a) Uncontrolled reaction (b) Cellular respiration
Explosive
release of
heat and light
energy
Controlled
release of
energy for
synthesis of
ATP
F
r
e
e

e
n
e
r
g
y
,

G

F
r
e
e

e
n
e
r
g
y
,

G

H
2
+
1
/
2
O
2
2 H

+

1
/
2
O
2
1
/
2
O
2
H
2
O
H
2
O
2 H
+
+ 2 e
-
2 e
-
2 H
+
ATP
ATP
ATP
E
l
e
c
t
r
o
n

t
r
a
n
s
p
o
r
t

c
h
a
i
n

(from food via NADH)
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)
Figure 9.6-3
Electrons
carried
via NADH
Electrons carried
via NADH and
FADH
2

Citric
acid
cycle
Pyruvate
oxidation
Acetyl CoA
Glycolysis
Glucose Pyruvate
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
CYTOSOL
MITOCHONDRION
ATP ATP
ATP
Substrate-level
phosphorylation
Substrate-level
phosphorylation
Oxidative
phosphorylation
The process that generates most of the ATP is called
oxidative phosphorylation because it is powered by redox
reactions
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 CO
2
and water by
respiration, the cell makes up to 32 molecules of ATP
Oxidative Phosphorylation
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 O
2
is present
Figure 9.8
Energy Investment Phase
Glucose
2 ADP + 2 P
4 ADP + 4 P
Energy Payoff Phase
2 NAD
+
+ 4 e
-
+ 4 H
+

2 Pyruvate + 2 H
2
O
2 ATP used
4 ATP formed
2 NADH + 2 H
+

Net
Glucose 2 Pyruvate + 2 H
2
O
2 ATP
2 NADH + 2 H
+
2 NAD
+
+ 4 e
-
+ 4 H
+

4 ATP formed - 2 ATP used
Figure 9.9a
Glycolysis: Energy Investment Phase
ATP
Glucose Glucose 6-phosphate
ADP
Hexokinase

1
Fructose 6-phosphate
Phosphogluco-
isomerase

2
Figure 9.9b
Glycolysis: Energy Investment Phase
ATP
Fructose 6-phosphate
ADP
3
Fructose 1,6-bisphosphate
Phospho-
fructokinase

4
5
Aldolase

Dihydroxyacetone
phosphate
Glyceraldehyde
3-phosphate
To
step 6
Isomerase

Figure 9.9c
Glycolysis: Energy Payoff Phase
2 NADH
2 ATP
2 ADP
2
2
2 NAD
+

+

2 H
+
2 P
i

3-Phospho-
glycerate
1,3-Bisphospho-
glycerate
Triose
phosphate
dehydrogenase
Phospho-
glycerokinase
6
7
Figure 9.9d
Glycolysis: Energy Payoff Phase
2 ATP
2 ADP
2 2 2 2
2 H
2
O
Pyruvate
Phosphoenol-
pyruvate (PEP)
2-Phospho-
glycerate
3-Phospho-
glycerate
8
9
10
Phospho-
glyceromutase
Enolase Pyruvate
kinase
After pyruvate is oxidized, the citric acid cycle completes
the energy-yielding oxidation of organic molecules
In the presence of O
2
, pyruvate enters the mitochondrion (in
eukaryotic cells) where the oxidation of glucose is completed
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
Pyruvate
Transport protein
CYTOSOL
MITOCHONDRION
CO
2
Coenzyme A
NAD
+
+

H
+
NADH
Acetyl CoA
1
2
3
The citric acid cycle,
also called the Krebs
cycle, completes the
break down of pyrvate
to CO
2

The cycle oxidizes
organic fuel derived
from pyruvate,
generating 1 ATP, 3
NADH, and 1 FADH
2

per turn
The Citric Acid
Cycle
Pyruvate
NAD
+

NADH
+ H
+
Acetyl CoA
CO
2

CoA
CoA
CoA
2 CO
2

ADP + P
i
FADH
2

FAD
ATP
3 NADH
3 NAD
+

Citric
acid
cycle
+ 3 H
+
NADH
1
Acetyl CoA
Citrate
Isocitrate
"-Ketoglutarate
Succinyl
CoA
Succinate
Fumarate
Malate
Citric
acid
cycle
NAD
+

NADH
NADH
FADH
2

ATP
+ H
+
+ H
+
+ H
+
NAD
+

NAD
+

H
2
O
H
2
O
ADP
GTP GDP
P
i

FAD
3
2
4
5
6
7
8
CoA-SH
CO
2

CoA-SH
CoA-SH
CO
2

Oxaloacetate
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 FADH
2

produced by the cycle
relay electrons extracted
from food to the electron
transport chain
Figure 9.12a
Acetyl CoA
Oxaloacetate
Citrate
Isocitrate
H
2
O
CoA-SH
1
2
Figure 9.12b
Isocitrate
"-Ketoglutarate
Succinyl
CoA
NADH
NADH
NAD
+

NAD
+

+ H
+
CoA-SH
CO
2

CO
2

3
4
+ H
+
Figure 9.12c
Fumarate
FADH
2

CoA-SH
6
Succinate
Succinyl
CoA
FAD
ADP
GTP GDP
P
i

ATP
5
Figure 9.12d
Oxaloacetate
8
Malate
Fumarate
H
2
O
NADH
NAD
+

+ H
+
7
During oxidative phosphorylation,
chemiosmosis couples electron transport to
ATP synthesis
Following glycolysis and the citric acid cycle, NADH and
FADH
2
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
Electrons are transferred from NADH or FADH
2
to the
electron transport chain
Electrons are passed through a number of proteins including
cytochromes (each with an iron atom) to O
2

The electron transport chain generates no ATP directly
It breaks the large free-energy drop from food to O
2
into
smaller steps that release energy in manageable amounts
The Pathway of
Electron Transport
The electron transport chain is
in the inner membrane
(cristae) of the mitochondrion
Most of the chains
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 O
2
,
forming H
2
O
NADH
FADH
2

2 H
+
+
1
/
2
O
2

2 e
-

2 e
-

2 e
-

H
2
O
NAD
+

Multiprotein
complexes
(originally from
NADH or FADH
2
)
I
II
III
IV
50
40
30
20
10
0
F
r
e
e

e
n
e
r
g
y

(
G
)

r
e
l
a
t
i
v
e

t
o

O
2

(
k
c
a
l
/
m
o
l
)

FMN
FeS
FeS
FAD
Q
Cyt b
Cyt c
1

Cyt c
Cyt a
Cyt a
3

FeS
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
INTERMEMBRANE SPACE
Rotor
Stator
H
+

Internal
rod
Catalytic
knob
ADP
+
P
i
ATP
MITOCHONDRIAL MATRIX
Protein
complex
of electron
carriers
(carrying electrons
from food)
Electron transport chain
Oxidative phosphorylation
Chemiosmosis
ATP
synth-
ase
I
II
III
IV
Q
Cyt c
FAD FADH
2

NADH
ADP + P
i

NAD
+

H
+

2 H
+
+
1
/
2
O
2
H
+

H
+

H
+

2 1
H
+

H
2
O

ATP
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
Electron shuttles
span membrane
MITOCHONDRION
2 NADH
2 NADH 2 NADH 6 NADH
2 FADH
2

2 FADH
2

or
+ 2 ATP + 2 ATP + about 26 or 28 ATP
Glycolysis
Glucose 2 Pyruvate
Pyruvate oxidation
2 Acetyl CoA
Citric
acid
cycle
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
CYTOSOL
Maximum per glucose:
About
30 or 32 ATP
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
There are several reasons why the number of ATP is not known exactly
Fermentation and anaerobic respiration enable
cells to produce ATP without the use of oxygen
Most cellular respiration requires O
2
to produce ATP
Without O
2
, the electron transport chain will cease to operate
In that case, glycolysis couples with fermentation or anaerobic
respiration to produce ATP
Anaerobic respiration uses an electron transport chain with a
final electron acceptor other than O
2
, for example sulfate
Fermentation uses substrate-level phosphorylation instead of
an electron transport chain to generate ATP
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
In alcohol fermentation, pyruvate is converted to ethanol in two
steps, with the first releasing CO
2
Alcohol fermentation by yeast is used in brewing, winemaking, and
baking
In lactic acid fermentation, pyruvate is reduced to NADH,
forming lactate as an end product, with no release of CO
2

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 O
2
is scarce
Figure 9.17
2 ADP
2 ATP
Glucose Glycolysis
2 Pyruvate
2 CO
2

2
+

2 NADH
2 Ethanol
2 Acetaldehyde
(a) Alcohol fermentation (b) Lactic acid fermentation
2 Lactate
2 Pyruvate
2 NADH
Glucose Glycolysis
2 ATP 2 ADP + 2 P
i

NAD
2 H
+
+ 2 P
i

2 NAD
+

+

+

2 H
+
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
The processes have different final electron acceptors: an organic
molecule (such as pyruvate or acetaldehyde) in fermentation and
O
2
in cellular respiration
Cellular respiration produces 32 ATP per glucose molecule;
fermentation produces 2 ATP per glucose molecule
Obligate anaerobes carry out fermentation or anaerobic
respiration and cannot survive in the presence of O
2

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
Figure 9.18
Glucose
CYTOSOL
Glycolysis
Pyruvate
No O
2
present:
Fermentation
O
2
present:
Aerobic cellular
respiration
Ethanol,
lactate, or
other products
Acetyl CoA
MITOCHONDRION
Citric
acid
cycle
Glycolysis and the citric acid cycle connect
to many other metabolic pathways
Gycolysis and the citric acid cycle are major intersections to various
catabolic and anabolic pathways
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; amino groups can
feed glycolysis or the citric acid cycle
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
Carbohydrates Proteins
Fatty
acids
Amino
acids
Sugars
Fats
Glycerol
Glycolysis
Glucose
Glyceraldehyde 3- P
NH
3

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