Cellular Respiration

Chapter Concepts
7.1 Aerobic Cellular Respiration
• During aerobic cellular respiration, the
breakdown of glucose drives the synthesis of
ATP. 118
• Aerobic cellular respiration requires a number of
reactions within three metabolic pathways. 119
7.2 Outside the Mitochondria: Glycolysis
• Glycolysis is a metabolic pathway that partially
breaks down glucose outside the mitochondria.
120

7.3 Inside the Mitochondria

• The transition reaction and the Krebs cycle,
which occur inside the mitochondria, continue
the breakdown of glucose until carbon dioxide
and water result. 122
• The electron transport system, which receives
electrons from NAD and FAD, produces most
of the ATP during aerobic cellular respiration.
124

7.4 Metabolic Pool and Biosynthesis

• A number of molecules in addition to glucose
can be broken down to drive ATP synthesis.
127

7.5 Fermentation
• Fermentation is a metabolic pathway that
partially breaks down glucose under anaerobic
conditions. 129
The well-developed muscles of these swimmers give them
strength. Muscles are powered by the energy of ATP, and
mitochondria are the organelles that convert the energy of various
organic compounds to the energy of ATP.

117

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 118 Part 1 Cell Biology
he long-distance runner breathes deeply and rhyth-
T mically as his legs keep up a steady beat along the
track. Internally, his body responds smoothly to
match the pace of his motions. Oxygen flowing into his lungs
enters the blood, passes through the heart and then ever
smaller blood vessels, until it is delivered to the cells of his
tissues. The intake of oxygen by the lungs and delivery by
the blood has been enhanced by his previous training. His
lung capacity is greater, his blood contains more red blood
cells, and the blood supply to his muscles is greater than in
those who do not train. His muscle cells are ready to receive
oxygen; they contain an abundance of mitochondria, which
start producing ATP as soon as oxygen has appeared.
Mitochondria are fueled by glucose breakdown. Glucose is
present because it has been stored in his muscle cells as
glycogen—the runner loaded up on carbohydrates a couple
of days before the race.
Respiration involves breathing and the transport of oxy-
gen to cells, but this chapter concerns only the use of energy
from the breakdown of organic molecules for the production
of ATP.
7.1 Aerobic Cellular Respiration
Aerobic cellular respiration includes all the various
metabolic pathways by which carbohydrates and other
molecules are broken down with the concomitant buildup
of ATP. The expression refers to pathways that require
oxygen, as indicated by the word aerobic, and results in a
complete breakdown of molecules to carbon dioxide (CO2)
and water (H2O). Figure 7.1 shows an overall equation for
aerobic cellular respiration, when glucose is the first
reactant.
Glucose is a high-energy molecule, and its breakdown
products, CO2 and H2O, are low-energy molecules. There-
fore, we would expect the process to be exergonic, that is,
releases energy:
Oxidation
C6H12O6 + 6 O2 6 CO2 + 6 H2O + energy
glucose
Reduction
As breakdown occurs, electrons are removed from sub-
strates and eventually are received by O2, which then com-
bines with H and becomes H2O. The equation shows
changes in regard to hydrogen atom (H) distribution. A hy-
drogen atom consists of a hydrogen ion plus an electron
(H + e). When hydrogen atoms are removed from glu-
cose, so are electrons. Since oxidation is the loss of electrons,
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7-2
O2
land O2 water
ADP + P ATP
C6H12O6 + 6 O2 6 CO2 + 6 H2O + ATP
glucose oxygen carbon water energy
dioxide
Figure 7.1 Aerobic cellular respiration.
Almost all organisms, whether they reside on land or in the water,
carry on aerobic cellular respiration, which is most often glucose
breakdown coupled to ATP buildup.
and reduction is the gain of electrons, glucose breakdown is
an oxidation-reduction reaction. Glucose is oxidized and O2
is reduced.
The buildup of ATP is an endergonic reaction, that is,
it requires energy. The overall equation for aerobic cellu-
lar respiration (Fig. 7.1) shows the coupling of glucose
breakdown to ATP buildup. As glucose is broken down,
ATP is built up, and this is the reason the ATP reaction is
drawn using a curved arrow above the glucose reaction
arrow. The breakdown of one glucose molecule results in
a maximum of 36 or 38 ATP molecules. This represents
about 40% of the potential energy within a glucose mole-
cule; the rest of the energy is lost as heat. This conversion
is more efficient than many others; for example, only
about 25% of the energy within gasoline is converted to
the motion of a car.
Phases of Aerobic Cellular Respiration
Aerobic cellular respiration does not occur all at once as in-
dicated by the overall reaction. If it did, all of the energy
within glucose would be given off at once and much of it
would be lost as heat. Instead, glucose breakdown involves
the four phases shown in Figure 7.2. Three of these are meta-
bolic pathways and one is an individual reaction:
• Glycolysis is the breakdown of glucose to two
molecules of pyruvate. Oxidation by removal of
hydrogen atoms provides enough energy for the
immediate buildup of two ATP. Glycolysis takes
place outside the mitochondria and does not utilize
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 7-3 Chapter 7 Cellular Respiration 119

glucose
C6

ATP Glycolysis

pyruvate
C3

CO2
Transition
reaction

acetyl group
C2

CO2 Krebs
Krebs
ATP cycle cycle

e–
H 2O Electron
ATP transport
system
e–
O2

Figure 7.2 Steps of aerobic cellular respiration.

Glycolysis, the transition reaction, the Krebs cycle, and the electron transport system are the four phases of aerobic cellular respiration which
results in 36 or 38 ATP per glucose molecule.

oxygen. The other stages of aerobic cellular
respiration take place inside the mitochondria,
where oxygen is utilized.
• During the transition reaction, pyruvate is oxidized
to an acetyl group carried by CoA, and CO2 is
removed. Since glycolysis ends with two molecules
of pyruvate, the transition reaction occurs twice per
glucose molecule.
• The Krebs cycle is a cyclical series of oxidation
reactions that give off CO2 and produce one ATP.
The Krebs cycle turns twice because two acetyl
CoA molecules enter the cycle per glucose
molecule. Altogether then, the Krebs cycle accounts
for two immediate ATP molecules per glucose
molecule.
• The electron transport system is a series of carriers
that accept the electrons removed from glucose and
pass them along from one carrier to the next until
they are finally received by O2. As the electrons pass
from a higher energy to a lower energy state, energy
is released and used for ATP buildup. The electrons
from one glucose result in 32 or 34 ATP, depending
on certain conditions.
Aerobic cellular respiration involves (1) glycolysis;
(2) the transition reaction; (3) the Krebs cycle; and
(4) the electron transport system. A total of 36 or
38 ATP molecules are produced per glucose
molecule in aerobic cellular respiration.

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 120 Part 1 Cell Biology 7-4

7.2 Outside the Mitochondria:

Glycolysis
Glycolysis, which takes place within the cytoplasm outside
the mitochondria, is the breakdown of glucose to two pyru-
vate molecules. Since glycolysis is universally found in or-
ganisms, it most likely evolved before the Krebs cycle and
the electron transport system. This may be why glycolysis
occurs in the cytoplasm and does not require oxygen.

Energy Investment Steps

As glycolysis begins, two ATP are used to activate glucose, a
C6 (six-carbon) molecule that splits into two C3 molecules,
each of which carries a phosphate group. From this point on,
each C3 molecule undergoes the same series of reactions. Note
that the left and right sides of Figure 7.3 are exactly the same.

Cytoplasm
Energy Harvesting Steps
During glycolysis, oxidation of substrates occurs by the re-
moval of electrons. However, these electrons are accompa-
nied by a hydrogen ion, so in effect two hydrogen atoms
(2e  2H) are removed. These are picked up by the coen-
zyme NAD (nicotinamide adenine dinucleotide):
NAD + 2H £ NADH  H
Later, when NADH passes two electrons on to another elec-
tron carrier, it becomes NAD again. Only a small amount
of NAD need be present in a cell, because like other coen-
zymes it is used over and over again.
Oxidation results in high-energy phosphate molecules
that allow the formation of four ATP. This is called
substrate-level phosphorylation because a substrate passes
a high-energy phosphate to ADP, and ATP results. Subtract-
ing the two ATP that were used to get started, there is a net
gain of two ATP from glycolysis (Fig. 7.3).
When glycolysis is a part of aerobic cellular respiration,
the end product pyruvate enters the mitochondria, where
oxygen is utilized. However, glycolysis does not need to be a.
a part of aerobic cellular respiration and can occur even Figure 7.3 Glycolysis.
when oxygen is not present in cells. As we will see on page (a) Glycolysis takes place in cytoplasm. (b) This pathway begins with
129, glycolysis is also a part of fermentation. Fermentation is glucose and ends with two pyruvate molecules; there is a gain of two
an anaerobic process; it does not require oxygen. NADH, and a net gain of two ATP from glycolysis.
Altogether the inputs and outputs of glycolysis are as
follows:

Glycolysis
inputs outputs

glucose 2 pyruvate
2 NAD+ 2 NADH
2 ATP
4 ATP (net 2 ATP)
4 ADP + 2 P

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 7-5 Chapter 7 Cellular Respiration 121

Energy Investment Steps

glucose
C6

ATP ATP 1. Two ATP are used

–2 ATP to activate glucose.

ADP ADP

P C6 P

2. A resulting C6 molecule breaks

down to 2 PGAL (glyceraldehyde
-2-phosphate) molecules.

PGAL PGAL
C3 P C3 P

Energy Harvesting Steps

P P
NAD+ NAD+ 3. Oxidation and phosphorylation of 2
PGAL results in 2 NADH and 2 high-
energy PGAP (1,3-bisphosphoglycerate)
NADH NADH molecules.

PGAP PGAP
P C3 P P C3 P
4. Removal of high-energy phosphate from
ADP ADP
2 PGAL by 2 ADP produces 2 ATP and
2 PGA (3-phosphoglycerate) molecules.

+2 ATP ATP ATP

PGA PGA
C3 P C3 P

5. Oxidation of 2 PGA by removal of

H 2O H2O water results in 2 high-energy PEP
(phosphoenolpyruvate) molecules.

PEP PEP
C3 P C3 P
ADP ADP

+2 ATP ATP ATP 6. Removal of high-energy phosphate

from 2 PGA by 2 ADP produces 2
pyruvate pyruvate ATP and 2 pyruvate molecules.
2 ATP C3 C3
(net gain)
b.
b.

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 122 Part 1 Cell Biology 7-6

cytosol: location of glycolysis

matrix: location of the transition

200 nm reaction and the Krebs cycle
cristae matrix

cristae: location of the electron

outer transport system
membrane

intermembrane inner
space membrane

Figure 7.4 Mitochondrion structure and function.

A mitochondrion is bounded by a double membrane, with an intermembrane space. The inner membrane invaginates to form the shelflike cristae.
The matrix is the fluid-filled interior of the mitochondrion. Note that glycolysis occurs outside the mitochondrion, whereas the Krebs cycle occurs
in the matrix and the electron transport system is located on the cristae, both within the mitochondrion.

7.3 Inside the Mitochondria M Carbon dioxide diffuses out of the cell and enters the blood-
stream. The bloodstream takes the CO2 to the lungs, where it
Whereas glycolysis takes place in the cytoplasm, the transi- is exchanged. The H2O can remain in the mitochondria, or
tion reaction, the Krebs cycle, and the electron transport sys- the cell, or enter the blood and be excreted by the kidneys as
tem all take place inside the cellular organelle called a need be.
mitochondrion. A mitochondrion has a double membrane,
with an intermembrane space (between the outer and inner Transition Reaction
membrane). Cristae are folds of inner membrane that jut out The transition reaction is so-called because it connects glycol-
into the matrix, the innermost compartment, which is filled ysis to the Krebs cycle. In this reaction, pyruvate is converted
with a gel-like fluid (Fig. 7.4). The transition reaction and the to a two-carbon acetyl group attached to coenzyme A, or CoA,
Krebs cycle enzymes are located in the matrix, and the elec- and CO2 is given off. This is an oxidation reaction in which
tron transport system is located in the cristae. Most of the electrons are removed from pyruvate by an enzyme that uses
ATP produced during cellular respiration is produced in mi- NAD as a coenzyme. NAD goes to NADH  H as acetyl-
tochondria; therefore, mitochondria are often called the CoA forms. This reaction occurs twice per glucose molecule.
powerhouses of the cell.
It is interesting to think about how our bodies provide
the reactants for aerobic cellular respiration. The air we
breathe contains oxygen, and the food we eat contains glu- 2 NAD+ 2 NADH + H+
cose. These enter the bloodstream, which carries them about
the body, and they move into each and every cell. The end
product of glycolysis, pyruvate, enters the mitochondria, 2 C3 H4 O3 + 2 CoA 2 C2 H3 O CoA + 2 CO2
where the transition reaction, the Krebs cycle, and electron
transport system occur. Eventually, pyruvate is completely
broken down to CO2 and H2O as ATP is produced. The CO2 2 pyruvate + 2 CoA 2 acetyl-CoA + 2 carbon
and ATP diffuse out of mitochondria into the cytoplasm. The dioxide
ATP is utilized in the cell for energy-requiring processes.

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 7-7 Chapter 7 Cellular Respiration 123

NADH
+
NAD

CO2
citrate
C6
1. The cycle begins when 2. Twice over, substrates
an acetyl group carried by are oxidized, NAD+ is
CoA
CoA combines with a C4 reduced to NADH,
molecule to form citrate. ketoglutarate and CO2 is released.
C5
NAD+
Acetyl-CoA
Krebs cycle
oxaloacetate
C4

NADH NADH

fumarate succinate
5. Once again a substrate C4 C4 CO2
NAD+ 3. ADP becomes ATP as a
is oxidized and NAD+
high-energy phosphate is
is reduced to NADH. FAD removed from a substrate.
ATP

4. Again a substrate
is oxidized but this
FADH2 time FAD is reduced
to FADH2.

Figure 7.5 Krebs cycle.

The net result of this cycle of reactions is the oxidation of an acetyl group to two molecules of CO2 along with a transfer of electrons to NAD and
FAD and a gain of one ATP. The Krebs cycle turns twice per glucose molecule.

Krebs Cycle tion is an important event of the Krebs cycle. When a high-
energy phosphate molecule gives up its phosphate group,
The Krebs cycle is a cyclical metabolic pathway located in ATP eventually results.
the matrix of mitochondria. The Krebs cycle, named for Sir The Krebs cycle turns twice for each original glucose
Hans Krebs, a British scientist, begins with the molecule cit- molecule. Therefore, the inputs and outputs of the Krebs
rate. For this reason, it is also known as the citric acid cycle cycle per glucose molecule are as follows:
(Fig. 7.5). During the Krebs cycle, the acetyl group that re-
sults from the transition reaction undergoes oxidation by the
removal of hydrogen atoms as two molecules of CO2 are Krebs Cycle
given off. inputs outputs
At the start of the Krebs cycle, the C2 acetyl group car-
ried by CoA joins with a C4 molecule, and citrate results. 2 acetyl groups 4 CO2
Oxidation occurs during the cycle not only by NAD but 2 ADP + 2 P 2 ATP
6 NAD+
also by FAD. FAD (flavin adenine dinucleotide) is another 6 NADH
2 FAD 2 FADH2
coenzyme of oxidation-reduction which is sometimes
used instead of NAD. After FAD accepts two electrons, it
becomes FADH2. During the Krebs cycle, electrons are ac-
cepted by NAD in three instances; FAD is used only We have now accounted for six carbon dioxide mole-
once. cules—two from the transition reaction and four from the
The two carbons of the acetyl group come off as CO2 as Krebs cycle. Carbon dioxide is one of the end products of
a part of the oxidation process. Substrate-level phosphoryla- aerobic cellular respiration.

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 124 Part 1 Cell Biology 7-8

Electron Transport System reduction

2e– NADH
NAD+ + H+
The electron transport system located in the cristae of the
mitochondria is a series of carriers that pass electrons from NADH
reductase
one to the other. Some of the electron carriers of the system ADP + P
are cytochromes; therefore, the system is also termed a cy-
tochrome system. Cytochromes are protein molecules with a oxidation
heme group that contains an iron atom (Fe) capable of being ATP
reduced and oxidized in a reversible manner. 2e–
The electrons that enter the electron transport system
2e–
are carried by NAD and FAD. Figure 7.6 is arranged to reduction
FADH 2
FAD + 2H
+
show that high-energy electrons enter the system, and low-
energy electrons leave the system. When NADH gives up its coenzyme
electrons, it becomes NAD; the next carrier gains the elec- Q
trons and is reduced. This oxidation-reduction reaction
starts the process, and each of the carriers in turn becomes oxidation
reduced and then oxidized as the electrons move down the
system. As the pair of electrons is passed from carrier to car- 2e–
rier, energy is released and used to form ATP molecules. reduction
Oxygen receives the energy-spent electrons from the last of
the carriers. After receiving electrons, oxygen combines with cytochrome
hydrogen ions and water forms: b, c1

oxidation ADP + P
1
2
O2 + 2 e – + 2 H + H2O
2e–
ATP

This manner of producing ATP is sometimes called oxida- reduction

tive phosphorylation because O2 must be present to re-
ceive electrons or the electron transport system does not cytochrome
work. c
When NADH delivers electrons to the first carrier of the
electron transport system, enough energy is released by the oxidation
time the electrons are received by O2 to permit the pro-
duction of three ATP molecules. When FADH2 delivers elec- 2e–
trons to the electron transport system, only two ATP are reduction
produced.
The cell needs only a limited supply of the coenzymes cytochrome c
NAD and FAD because they are constantly being recycled oxidase
ADP + P
and reused. Therefore, once NADH has delivered electrons
to the electron transport system, it is “free” to return and oxidation
pick up more hydrogen atoms. In the same manner, the com-
ATP
ponents of ATP are recycled in cells. Energy is required to
join ADP +  P , and then when ATP is used to do cellular 2e–
work, ADP and  P result once more. The recycling of coen-
zymes and ADP increases cellular efficiency since it does 2H+
away with the necessity to synthesize NAD, FAD, and
ADP anew. 1
2 O2 H 2O

As electrons pass down the electron transport
system, energy is released and ATP is produced.
Figure 7.6 Overview of the electron transport system.
NADH and FADH2 bring electrons to the electron transport system.
As the electrons move down the system, energy is released and used
to form ATP. For every pair of electrons that enters by way of NADH,
three ATP result. For every pair of electrons that enters by way of
FADH2, two ATP result. Oxygen, the final acceptor of the electrons,
becomes a part of water.

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 7-9 Chapter 7 Cellular Respiration 125

Organization of Cristae intermembrane space of a mitochondrion. The vertical ar-

Figure 7.6 is a simplified overview of the electron transport rows in Figure 7.8 show that the first complex, called the
system. Figure 7.7 shows how the electron transport system NADH dehydrogenase complex, the cytochrome b–c1 com-
consists of three protein complexes and two mobile carriers. plex, and the cytochrome c oxidase complex all pump H
The mobile carriers transport electrons between the com- into the intermembrane space. This establishes a very
plexes, which also contain electron carriers. strong electrochemical gradient; there are many hydrogen
Thus far we have been stressing that the carriers accept ions in the intermembrane space and few in the matrix of a
electrons, which they pass from one to the other. What hap- mitochondrion.
pens to the hydrogen ions (H) carried by NADH and The cristae also contain an ATP synthase complex through
FADH2? The carriers of the electron transport system use which hydrogen ions flow down their gradient from the
the energy released by electrons as they move down the intermembrane space into the matrix. As hydrogen ions
electron transport system to pump hydrogen ions into the flow from high to low concentration, energy is released,
allowing the enzyme ATP synthase to synthesize ATP from

ADP +  P . Just how H flow drives ATP synthesis is not
known; perhaps the hydrogen ions
participate in the reaction, or perhaps
they cause a change in the shape of ATP
NADH cytochrome b,c1
dehydrogenase H+ complex H+ synthase and this brings about ATP syn-
H+
complex H + thesis. Mitochondria produce ATP by
H+ chemiosmosis, so-called because ATP
H+ H+ H+ H+ production is tied to an electrochemical
H+ cytochrome c
oxidase
gradient that is an H gradient.
complex Once formed, ATP molecules dif-
fuse out of the mitochondrial matrix by
e– way of a channel protein.
H+

e– Mitochondria utilize ATP

e–
synthesis by chemiosmosis.
FADH2 FAD + 2 H+ e–
H+ ATP production is dependent
H+ upon an electrochemical
NADH H+ NAD+ 2 H+ + 1
2
O2 gradient established by the
pumping of H into the
electron transport system intermembrane space.

H 2O
ATP H+ H+
ADP + P
Matrix

H+

H+

ATP channel ATP synthase

protein complex Intermembrane
ATP H+ Space

Figure 7.7 Organization of cristae.

The electron transport system is located in the cristae. As electrons (e) move from one
complex to the other, hydrogen ions (H) are pumped from the matrix into the intermembrane
space. As hydrogen ions flow down their concentration gradient from the intermembrane
space into the matrix, ATP is synthesized by an ATP synthase. ATP leaves the matrix by way
of a channel protein.

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 126 Part 1 Cell Biology 7-10

Energy Yield From Glucose Metabolism
Figure 7.8 calculates the ATP yield for the complete break-
down of glucose to CO2 and H2O. Notice that the diagram in-
cludes the number of ATP produced directly by glycolysis and
the Krebs cycle and the number that is produced as a result of
electrons passing down the electron transport system.
Per glucose molecule, there is a net gain of two ATP
from glycolysis, which takes place in the cytoplasm. The
Krebs cycle, which occurs in the matrix of mitochondria, ac-
counts for two ATP per glucose molecule. This means that
there is a total of four ATP formed outside the electron trans-
port system.
Most ATP is produced by the electron transport system.
Per glucose molecule, ten NADH and two FADH2 take elec-
trons to the electron transport system. For each NADH
formed inside the mitochondria by the Krebs cycle, three
ATP result, but for each FADH2, there are only two ATP pro-
duced. Figure 7.6 explains the reason for this difference:
FADH2 delivers its electrons to the transport system after
NADH, and therefore these electrons cannot account for as
much ATP production.
What about the ATP yield of NADH generated outside
the mitochondria by the glycolytic pathway? NADH cannot
cross mitochondrial membranes, but there is a “shuttle”
mechanism that allows its electrons to be delivered to the
electron transport system inside the mitochondria. The shut-
tle consists of an organic molecule, which can cross the outer
membrane, accept the electrons, and in most but not all cells,
deliver them to a FAD molecule in the inner membrane. If
FAD is used, only two ATP result because the electrons have
not entered the start of the electron transport system.
Efficiency of Aerobic Respiration
It is interesting to calculate how much of the energy in a glu-
cose molecule eventually becomes available to the cell. The
difference in energy content between the reactants (glucose
and O2) and the products (CO2 and H2O) is 686 kcal. An ATP
phosphate bond has an energy content of 7.3 kcal, and 36 of
these are usually produced during glucose breakdown; 36
phosphates are equivalent to a total of 263 kcal. Therefore,
263/686, or 39%, of the available energy is usually trans-
ferred from glucose to ATP. The rest of the energy is lost in
the form of heat.

glucose
Cytoplasm

glycolysis
2 ATP
2 NADH 4 or 6 ATP
2 pyruvate
Electron Transport System

2 NADH 6 ATP
2 acetyl-CoA

2 CO2
Mitochondrion

6 NADH 18 ATP

Krebs
cycle
2 ATP
2 FADH2 4 ATP
4 CO2

O2 H2O

ATP Yield 4 ATP

+ 32 or 34 ATP

36 or 38 ATP

Figure 7.8 Accounting of energy yield per glucose molecule breakdown.

Substrate-level phosphorylation during glycolysis and the Krebs cycle accounts for four ATP. Oxidative phosphorylation accounts for 32 or 34
ATP, and the grand total of ATP is therefore 36 or 38 ATP. Cells differ as to the delivery of the electrons from NADH generated outside the
mitochondria. If they are delivered by a shuttle mechanism to the start of the electron transport system, 6 ATP result; otherwise, 4 ATP result.

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 7-11 Chapter 7 Cellular Respiration 127

7.4 Metabolic Pool and Biosynthesis
Degradative reactions, which participate in catabolism,
break down molecules and tend to be exergonic. Synthetic
reactions, which participate in anabolism, tend to be ender-
gonic. It is correct to say that catabolism drives anabolism
because catabolism results in an ATP buildup that is used by
anabolism.
Catabolism
We already know that glucose is broken down during aero-
bic cellular respiration. However, other molecules can also
undergo catabolism. When a fat is used as an energy source,
it breaks down to glycerol and three fatty acids. As Figure
7.9 indicates, glycerol is converted to PGAL, a metabolite in
glycolysis. The fatty acids are converted to acetyl-CoA,
which enters the Krebs cycle. An 18-carbon fatty acid results
in nine acetyl-CoA molecules. Calculation shows that respi-
ration of these can produce a total of 216 ATP molecules. For
this reason, fats are an efficient form of stored energy—there
are three long fatty acid chains per fat molecule.
The carbon skeleton of amino acids can also be broken
down. The carbon skeleton is produced in the liver when an
amino acid undergoes deamination, or the removal of the
amino group. The amino group becomes ammonia (NH3),
which enters the urea cycle and becomes part of urea, the
primary excretory product of humans. Just where the carbon
skeleton begins degradation is dependent on the length of
the R group, since this determines the number of carbons
left after deamination.

glucose
Anabolism
C6 glycogen
We have already mentioned that the ATP produced
during catabolism drives anabolism. But there is an-
other way catabolism is related to anabolism. The
substrates making up the pathways in Figure 7.9 can
C6 – P be used as starting materials for synthetic reactions.
In other words, compounds that enter the pathways
are oxidized to substrates that can be used for biosyn-
thesis. This is the cell’s metabolic pool, in which one
type of molecule can be converted to another. In this
glycerol PGAL way, carbohydrate intake can result in the formation
C3 C3 – P
of fat. PGAL can be converted to glycerol, and acetyl
groups can be joined to form fatty acids. Fat synthesis
follows. This explains why you gain weight from eat-
lactate pyruvate ing too much candy, ice cream, and cake.
C3 C3
proteins Some substrates of the Krebs cycle can be con-
fats verted to amino acids through transamination, the
transfer of an amino group to an organic acid, form-
ing a different amino acid. Plants are able to synthe-
size all of the amino acids they need. Animals,
however, lack some of the enzymes necessary for syn-
fatty acids acetyl-CoA amino acids thesis of all amino acids. Adult humans, for example,
(C2)n C2 NH2 – CH – COOH
can synthesize 11 of the common amino acids, but
R they cannot synthesize the other 9. The amino acids
that cannot be synthesized must be supplied by the
deamination diet; they are called the essential amino acids. The
nonessential amino acids can be synthesized. It is
quite possible for animals to suffer from protein defi-
Krebs NH3 ciency if their diets do not contain adequate quanti-
cycle
ties of all the essential amino acids.

All the reactions involved in aerobic cellular

Figure 7.9 The metabolic pool concept.
Carbohydrates, fats, and proteins can be used as energy sources, and they
enter degradative pathways at specific points. Catabolism produces molecules
that can also be used for anabolism of other compounds.
respiration are a part of a metabolic pool;
the molecules from the pool can be used for
catabolism or for anabolism.

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 Exercise: A Test of Homeostatic Control
Exercise is a dramatic test of the body’s homeostatic control sys- Training also results in greater reliance on the Krebs cycle
tems—there is a large increase in muscle oxygen (O2) require- and increased fatty acid metabolism, because fatty acids are bro-
ment, and a large amount of carbon dioxide (CO2) is produced. ken down to acetyl-CoA, which enters the Krebs cycle. This pre-
These changes must be countered by increases in breathing and serves plasma glucose concentration and also helps the body
blood flow to increase O2 delivery and remove the metabolically maintain homeostasis.
produced CO2. Also, heavy exer-
cise can produce a large amount of
lactic acid due to the utilization of In athletes, there is:
fermentation, an anaerobic process. a smaller O2 deficit due to a more rapid increase in O2 uptake at the onset of work;
Both the accumulation of CO2 an increase in fat metabolism that spares blood glucose;
and lactic acid can lead to an in- a reduction in lactate and H+ formation;
crease in intracellular and extracel- an increase in lactate removal.
lular activity. Further, during heavy
exercise, the working muscles pro-
duce large amounts of heat that
must be removed to prevent over-
heating. In a strict sense, the body
rarely maintains true homeostasis
while performing intense exercise
or during prolonged exercise in a
hot or humid environment. How-
ever, a better maintenance of home-
ostasis is observed in those who
have had endurance training.
The number of mitochondria in-
creases in the muscles of persons
who train; therefore, there is
greater reliance on the Krebs cycle
and the electron transport system
to generate energy. Muscle cells
with few mitochondria must have a
high ADP concentration to stimu-
late the limited number of mito-
chondria to start consuming O2.
After an endurance training pro-
gram, the large number of mito-
chondria start consuming O2 as
soon as the ADP concentration
starts rising due to muscle contrac-
tion and subsequent breakdown of
ATP. Therefore, a steady state of O2
intake by mitochondria is achieved
earlier in the athlete. This faster rise
in O2 uptake at the onset of work
means that the O2 deficit is less,
and the formation of lactate due to
fermentation is less. Further, any
lactate that is produced is removed
and processed more quickly.

128

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 7-13 Chapter 7 Cellular Respiration 129

7.5 Fermentation glucose

C6
Fermentation consists of glycolysis plus one other
2 ATP
reaction—the reduction of pyruvate to either lactate or alco-
hol and CO2 (Fig. 7.10). The pathway operates anaerobically
because after NADH transfers its electrons to pyruvate, it is 2 ADP
“free” to return and pick up more electrons during the ear- 2
lier reactions of glycolysis. PGAL
Certain anaerobic bacteria such as lactic-acid bacteria, C3 P
which help us manufacture cheese, consistently produce lac-
tate in this manner. Other bacteria anaerobically produce
2 P
chemicals of industrial importance: isopropanol, butyric 2 NAD+
acid, propionic acid, and acetic acid. Yeasts are good exam-
ples of organisms that generate alcohol and CO2. Yeast is 2 NADH
used to leaven bread; the CO2 produced makes bread rise.
Yeast is also used to ferment wine; in that case, it is the ethyl 2
alcohol that is desired. Eventually yeasts are killed by the PGAP
very alcohol they produce. P C3 P
Animal, including human, cells are similar to lactic
4 ADP
acid bacteria in that pyruvate, when produced faster than
it can be oxidized through the Krebs cycle, is reduced to
lactate. 4 ATP
2
pyruvate
Advantages and Disadvantages of C3
2 NADH

Fermentation
Despite its low yield of only two ATP, fermentation is essen- 2 NAD+
tial to humans because it can provide a rapid burst of ATP;
muscle cells more than other cells are apt to carry on fer-
mentation. When our muscles are working vigorously over
a short period of time, as when we run, fermentation is a or
way to produce ATP even though oxygen is temporarily in a
limited supply. 2 lactate (C3) 2 alcohol (C2) and
2 CO2
Lactate, however, is toxic to cells. At first, blood carries
away all the lactate formed in muscles. Eventually, however,
lactate begins to build up, changing the pH and causing the Figure 7.10 Fermentation.
muscles to fatigue so that they no longer contract. When we Fermentation consists of glycolysis followed by a reduction of
pyruvate. This “frees” NAD, and it returns to the glycolytic pathway
stop running, our bodies are in oxygen debt, as signified by
to pick up more electrons.
the fact that we continue to breathe very heavily for a time. Re-
covery is complete when the lactate is transported to the liver,
where it is reconverted to pyruvate. Some of the pyruvate is
respired completely, and the rest is converted back to glucose.

Efficiency of Fermentation
The two ATP produced per glucose molecule during fer-
mentation is equivalent to 14.6 kcal. Complete glucose
molecule breakdown to CO2 and H2O represents a possible Fermentation
energy yield of 686 kcal per molecule. Therefore, the effi- inputs outputs
ciency for fermentation is only 14.6/686, or 2.1%. This is 2 lactate or
glucose
much less efficient than the complete breakdown of glu- 2 alcohol and 2 CO2
2 ATP
cose. The inputs and outputs of fermentation are as shown 4 ATP (net 2 ATP)
4 ADP + 2 P
in the illustration to the right.

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 130 Part 1 Cell Biology 7-14

F eeling tired and run down? Want to

jump start your mitochondria? If you
have iron deficiency anemia, you could
take iron tablets to encourage your body to
build more hemoglobin, the substance that
carries oxygen in your blood. If you are di-
abetic, medications are available to make
sure glucose is entering your cells. How-
ever, if you seem to have no specific ail-
ment, you might be tempted to turn to
what is now called alternative medicine.
Alternative medicine includes such non-
conventional therapies as herbal supple-
ments, acupuncture, chiropractic therapy,
homeopathy, osteopathy, and therapeutic
touch (e.g., the laying on of hands).
Advocates of alternative medicine
have made some headway in having alter-
native medicine practices accepted by
most anyone. In 1992, congress established
what is now called the National Center for
Complementary and Alternative Medicine
(NCCAM), whose budget has grown from
$2 million to its present $50 million for
1999. Then in 1994, the Dietary Supple-
ment Health and Education Act allowed
the marketing of vitamins, minerals, and
herbs without the requirement that they
be approved by the Food and Drug Ad-
ministration (FDA).
Many scientists feel that alternative
medicine should be subjected to the same
rigorous clinical testing as traditional
medicine. They approve of a study that is
now testing the efficacy of the herb St.
John’s wort, for example. In the study, 336
patients diagnosed with moderate depres-
sion will be divided into three groups. One
group will receive the herb St. John’s wort;
another will be given sertraline, a tradi-
tional medicine, and a third group will re-
ceive a placebo. The results are expected to
tell whether St. John’s wort, a relatively in-
expensive remedy, works just as well as a
relatively expensive drug produced by
pharmaceutical firms.
Questions Go To Student OLC
1. Do you believe that alternative medical
practices should be subjected to clinical
testing, or do you believe the public
should simply rely on “word of mouth”
recommendations?
2. What changes do you anticipate if
alternative medical practices were to
become a regular part of traditional
medicine?
3. Would it be acceptable to you if it could be
shown that alternative medical practices
succeed simply for psychological reasons
rather than for their physical benefits?

complexes on the cristae of the mitochondria. Each protein complex re-

Summarizing the Concepts
7.1 Aerobic Cellular Respiration
During aerobic cellular respiration, glucose is oxidized to CO2 and
H2O. This exergonic reaction drives ATP buildup, an endergonic reac-
tion. Four phases are required: glycolysis, the transition reaction, the
Krebs cycle, and the electron transport system. Oxidation occurs by the
removal of hydrogen atoms (e + H) from substrate molecules.
7.2 Outside the Mitochondria: Glycolysis
Glycolysis, the breakdown of glucose to two pyruvate, is a series of en-
zymatic reactions that occur in the cytoplasm. Oxidation by NAD re-
leases enough energy immediately to give a net gain of two ATP by
substrate-level phosphorylation. Two NADH are formed.
7.3 Inside the Mitochondria
Pyruvate from glycolysis enters a mitochondrion, where the transition
reaction takes place. During this reaction, oxidation occurs as CO2 is re-
moved. NAD is reduced, and CoA receives the C2 acetyl group that
remains. Since the reaction must take place twice per glucose, two
NADH result.
The acetyl group enters the Krebs cycle, a cyclical series of reac-
tions located in the mitochondrial matrix. Complete oxidation follows,
as two CO2, three NADH, and one FADH2 are formed. The cycle also
produces one ATP. The entire cycle must turn twice per glucose mole-
cule.
The final stage of glucose breakdown involves the electron trans-
port system located in the cristae of the mitochondria. The electrons re-
ceived from NADH and FADH2 are passed down a chain of carriers
until they are finally received by O2, which combines with H to pro-
duce H2O. As the electrons pass down the chain, ATP is produced. The
term oxidative phosphorylation is sometimes used for ATP production
by the electron transport system.
The carriers of the electron transport system are located in protein
ceives electrons and pumps H into the intermembrane space, setting
up an electrochemical gradient. When H flows down this gradient
through the ATP synthase complex, energy is released and used to
form ATP molecules from ADP and  P . This is ATP synthesis by
chemiosmosis.
To calculate the total number of ATP per glucose breakdown, con-
sider that for each NADH formed inside the mitochondrion, three ATP
are produced. In most cells, each NADH formed in the cytoplasm results
in only two ATP. This is because the carrier that shuttles the hydrogen
atoms across the mitochondrial outer membrane usually passes them to
an FAD. Each molecule of FADH2 results in the formation of only two
ATP because the electrons enter the electron transport system at a lower
energy level than NADH. Of the 36 or 38 ATP formed by aerobic cellular
respiration, four occur outside the electron transport system: two are
formed directly by glycolysis and two are formed directly by the Krebs
cycle. The rest are produced by the electron transport system.
7.4 Metabolic Pool and Biosynthesis
Carbohydrate, protein, and fat can be broken down by entering the
degradative pathways at different locations. These pathways also pro-
vide molecules needed for the synthesis of various important sub-
stances. Catabolism and anabolism, therefore, both utilize the same
metabolic pool of reactants.
7.5 Fermentation
Fermentation involves glycolysis, followed by the reduction of pyru-
vate by NADH to either lactate or alcohol and CO2. The reduction
process “frees” NAD so that it can accept more electrons during gly-
colysis.
Although fermentation results in only two ATP, it still serves a
purpose: In humans, it provides a quick burst of ATP energy for short-
term, strenuous muscular activity. The accumulation of lactate puts the
individual in oxygen debt because oxygen is needed when lactate is
completely metabolized to CO2 and H2O.

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 7-15 Chapter 7 Cellular Respiration 131

7. Which of these is not true of fermentation?

Studying the Concepts a. net gain of only two ATP d. begins with glucose
b. occurs in cytoplasm e. carried on by yeast
1. What is the equation for aerobic cellular respiration? Explain
c. NADH donates electrons to electron transport system
how this is an oxidation-reduction reaction. Why is the reac-
For questions 8–10, match the items below to one of the locations in the
tion able to drive ATP buildup? 118
key.
2. What are the four phases occurring during aerobic cellular
Key:
respiration? 119
a. matrix of the mitochondrion
3. Define glycolysis; what are its inputs and outputs? 120
b. cristae of the mitochondrion
4. What portions of aerobic cellular respiration occur inside
c. the intermembrane space of mitochondrion
mitochondria? How does a human being acquire the needed
d. in the cytoplasm
substrates, and what happens to the products? 122
e. None of these are correct.
5. Give the substrates and products of the transition reaction.
8. electron transport system
Where does it take place? 122
9. glycolysis
6. What happens to the acetyl group that enters the Krebs cycle?
10. accumulation of hydrogen ions (H)
What are the other steps in this cycle? 123
11. Label this diagram of a mitochondrion.
7. What are NAD and FADH2, and what role do they play in
aerobic cellular respiration? 120, 123
8. What is the electron transport system, and what are its func- a. b.
tions? 124
9. Describe the organization of protein complexes within the
cristae. 125
10. Calculate the energy yield of aerobic cellular respiration per
glucose molecule. 126
11. Give examples to support the concept of the metabolic pool.
127
12. What is fermentation and how does it differ from glycolysis?
Mention the benefit of pyruvate reduction during fermenta-
tion. What types of organisms carry out lactate fermentation, c.
and what types carry out alcoholic fermentation? 129 d. e.

Testing Yourself Understanding the Terms

Choose the best answer for each question. For questions 1–3, iden-
acetyl-CoA 122 fermentation 129
tify the pathway involved by matching them to the terms in the
aerobic 118 glycolysis 119
key.
aerobic cellular respiration Krebs cycle 119
Key:
118 metabolic pool 127
a. glycolysis
anabolism 127 mitochondrion 122
b. Krebs cycle
anaerobic 120 NAD (nicotinamide adenine
c. electron transport system
catabolism 127 dinucleotide) 120
1. carbon dioxide (CO2) given off
chemiosmosis 125 oxidative phosphorylation
2. PGAL
cytochrome 124 124
3. cytochrome carriers
deamination 127 oxygen debt 129
4. The greatest contributor of electrons to the electron transport
electron carrier 124 pyruvate 119
system is
electron transport system 119 substrate-level phosphoryla-
a. oxygen. d. the transition reaction.
FAD (flavin adenine dinu- tion 120
b. glycolysis. e. fermentation.
cleotide) 123 transition reaction 119
c. the Krebs cycle.
5. Substrate-level phosphorylation takes place in Match the terms to these definitions:
a. glycolysis and the Krebs cycle. a. Cycle of reactions in mitochondria that begins
b. the electron transport system and the transition reaction. with citric acid; it produces CO2, ATP, NADH, and FADH2;
c. glycolysis and the electron transport system. also called the citric acid cycle.
d. the Krebs cycle and the transition reaction.
b. Growing or metabolizing in the absence of oxygen.
6. Fatty acids are broken down to
a. pyruvate molecules, which take electrons to the electron c. Anaerobic breakdown of glucose that results in a
transport system. gain of two ATP and end products such as alcohol and lactate.
b. acetyl groups, which enter the Krebs cycle. d. End product of glycolysis; pyruvic acid.
c. glycerol, which is found in fats. e. Passage of electrons along a series of membrane-
d. amino acids, which excrete ammonia. bounded carrier molecules from a higher to lower energy
e. All of these are correct. level; the energy released is used for the synthesis of ATP.

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 132 Part 1 Cell Biology
Thinking Scientifically
1. Considering aspects of cellular respiration (page 118)
a. The body breathes in oxygen (O2). What exact function
does oxygen perform in the body?
b. The body breathes out carbon dioxide (CO2). Exactly how
does the body produce carbon dioxide?
c. Just before a competition, athletes eat carbohydrates. Why
does the intake of carbohydrates ensure them a supply of
energy for the athletic event?
2. The drug dinitrophenol makes the inner mitochondrial mem-
brane leaky to hydrogen ions (H+),
a. In which direction would you expect the H+ to leak, from
the intermembrane space to the matrix or the reverse? Why?
b. What effect would this drug have on ATP production?
Why?
c. What effect would this drug have on stored glycogen and
lipid supplies?
d. Would you recommend this drug for weight loss? Why or
why not?
Using Technology
Your study of cellular respiration is supported by these available
technologies:
Essential Study Partner CD-ROM
Cells £ Respiration
Visit the Mader web site for related ESP activities.
Exploring the Internet
The Mader Home Page provides resources and tools as
you study this chapter.
http://www.mhhe.com/biosci/genbio/mader
Life Science Animations 3D Video
9 Electron Transport Chain
Further Readings for Part 1
Armbruster, P., and Hessberger, F. P. September 1998. Making new
elements. Scientific American 279(3):72. The process of creating
new artificial elements is examined.
Bayley, H. September 1997. Building doors into cells. Scientific
American 277(3):62. Protein engineers are designing artificial
pores for drug delivery.
Becker, W. M., and Deamer, D. W. 1996. The world of the cell. 3d ed.
Redwood City, Calif.: Benjamin/Cummings Publishing.
Presents an overview of cell biology.
Back Forward Main Menu TOC Study Guide TOC
7-16
Caret, R. L., et al. 1997. Principles and applications of organic and
biological chemistry. 2d ed. Dubuque, Iowa: Wm. C. Brown
Publishers. For undergraduates in the allied health fields, this
text emphasizes material unique to health-related studies.
Chang, R. 1998. Chemistry. 6th ed. Dubuque, Iowa: McGraw-Hill.
This general chemistry text provides a foundation in chemical
concepts and principles, and presents topics clearly.
Chapman, C. 1999. Basic chemistry for biology. 2d ed.
WCB/McGraw-Hill. The goal of this workbook is to provide
a review of basic principles for biology students.
Ford, B. J. April 1998. The earliest views. Scientific American
278(4):50. Presents experiments of early microscopists.
Frank, J. September/October 1998. How the ribosome works.
American Scientist 86(5):428. New imaging techniques using
cryo-electron microscopy allows researchers to study a three-
dimensional map of the ribosome.
Gerstein, M., and Levitt, M. November 1998. Simulating water
and the molecules of life. Scientific American 279(5):100.
Computer models show how water affects the structure and
movement of proteins and other biological molecules.
Ingber, D. E. January 1998. The architecture of life. Scientific
American 278(1):48. Simple mechanical rules may govern cell
movements, tissue organization, and organ development.
Lang, F., and Waldegger, S. September/October1997. Regulating
cell volume. American Scientist 85(5):456. Changes in cell
volume may threaten organ or tissue function.
Lasic, D. D. May/June 1996. Liposomes. Science & Medicine
3(3):34. Liposomes can deliver genes or drugs for gene
therapy.
Nemecek, S. October 1997. Gotta know when to fold ‘em. Scientific
American 277(4):28. Details about how proteins fold are
discussed.
Nurse, P., et al. October 1998. Understanding the cell cycle. Nature
Medicine 4(1):1103. Gives the relevance of cell-cycle research.
Ojcius, D. M., et al. January/February 1998. Pore-forming
proteins. Science & Medicine 5(1):44. Peptide molecules that
cause pore formation in membranes are similar in structure
and function.
Scerri, E. R. November/December 1997. The periodic table and
the electron. American Scientist 85(6):546. Electron
configurations may only give an approximate explanation of
the periodic table.
Scerri, E. R. September 1998. The evolution of the periodic system.
Scientific American 279(3):78. Article discusses the history and
evolution of the periodic table.
Schwartz, A. T., et al. 1997. Chemistry in context: Applying chemistry
to society. 2d ed. Dubuque, Iowa: Wm. C. Brown Publishers.
This introductory text is designed for students in the allied
health fields.
Sperelakis, N., editor. 1998. Cell physiology source book. 2d ed. San
Diego: Academic Press. For advanced biology students, this is
a comprehensive and authoritative text covering topics in cell
physiology written by experts in the field.
Stix, G. October 1997. Growing a new field. Scientific American
277(4):15. Tissue engineers try to grow organs in the
laboratory.
Zubay, G. L. 1998. Biochemistry. 4th ed. Dubuque, Iowa: Wm. C.
Brown Publishers. This text for chemistry majors relates
biochemistry to cell biology, physiology, and genetics.
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