1. Part 3 Metabolism and Energy Balance
Energy Metabolism
Life depends on energy from the sun.
During photosynthesis, plants transform
solar energy into chemical energy
in the form of carbohydrates. During
energy metabolism, we transform this
chemical energy into ATP. Learn more
at health.nih.gov.

2. 9.1 Metabolism: Chemical Reactions in
the Body
9.2 ATP Production from Carbohydrates
9.3 ATP Production from Fats
9.4 Protein Metabolism
9.5 Alcohol Metabolism
9.6 Regulation of Energy Metabolism
9.7 Fasting and Feasting
Medical Perspective: Inborn Errors of
Metabolism
STUDENT LEARNING OUTCOMES
after studying this chapter, you will be able to
1. Explain the differences among metabolism, 5. Identify the conditions that lead to ketogenesis
catabolism, and anabolism. and its importance in survival during fasting.
2. Describe aerobic and anaerobic metabolism of 6. Describe the process of gluconeogenesis.
glucose. 7. Discuss how the body metabolizes alcohol.
3. Illustrate how energy is extracted from 8. Compare the fate of energy from
glucose, fatty acids, amino acids, and alcohol macronutrients during the fed and fasted
using metabolic pathways, such as glycolysis, states.
beta-oxidation, the citric acid cycle, and the
electron transport system. 9. Describe common inborn errors of metabolism.
4. Describe the role that acetyl-CoA plays in cell
metabolism.
The macronutrients and alcohol are rich sources of energy; however, the energy they provide is
neither in the form that cells can use nor in the amount needed to carry out the thousands of chemical
reactions that occur every day in the human body. Thus, the body must have a process for breaking
down energy-yielding compounds to release and convert their chemical energy to a form the body can
use.1 That process is energy metabolism—an elaborate, multistep series of energy-transforming chemical
reactions. Energy metabolism occurs in all cells every moment of every day for your entire lifetime; it is
slowest when we are resting and fastest when we are physically active.
Understanding energy metabolism clarifies how carbohydrates, proteins, fats, and alcohol
are interrelated and how they serve as fuel for body cells. In this chapter, you will see how the
macronutrients and alcohol are metabolized and discover why proteins can be converted to glucose
but most fatty acids cannot. Studying energy metabolism pathways in the cell also sets the stage for
examining the roles of vitamins and minerals. As you’ll see in this and subsequent chapters, many
micronutrients contribute to the enzyme activity that supports metabolic reactions in the cell.2 Thus,
both macronutrients and micronutrients are required for basic metabolic processes.
281

3. 282 Part 3 Metabolism and Energy Balance
Proteins
Glycogen 9.1 Metabolism: Chemical Reactions in the Body
Protein Triglycerides
Carbohydrate and other
Fat lipids Metabolism refers to the entire network of chemical processes involved in maintaining
C life. It encompasses all the sequences of chemical reactions that occur in the body. Some
A of these biochemical reactions enable us to release and use energy from carbohydrate,
T
A fat, protein, and alcohol. They also permit us to synthesize 1 substance from another and
B A prepare waste products for excretion.1 A group of biochemical reactions that occur in a
O N
L A progression from beginning to end is called a metabolic pathway. Compounds formed
I B in 1 of the many steps in a metabolic pathway are called intermediates.
S O
M L All of the pathways that take place within the body can be categorized as either ana-
I bolic or catabolic. Anabolic pathways use small, simpler compounds to build larger, more
S
M complex compounds (Fig. 9-1). The human body uses compounds, such as glucose, fatty
acids, cholesterol, and amino acids, as building blocks to synthesize new compounds,
CO2 Amino acids such as glycogen, hormones, enzymes, and other proteins, to keep the body functioning
H2O Sugars
Fatty acids
and to support normal growth and development. For example, to make glycogen (a stor-
NH3 Glycerol age form of carbohydrate), we link many units of the simple sugar glucose. Energy must
be expended for anabolic pathways to take place.
Conversely, catabolic pathways break down compounds into small units. The gly-
Figure 9-1 Anabolism relies on catabolism cogen molecule discussed in the anabolism example is broken down into many glucose
to provide the energy (ATP) required to build
compounds.
molecules when blood levels of glucose drop. Later, the complete catabolism of this glu-
cose results in the release of carbon dioxide (CO2) and water (H2O). Energy is released
during catabolism: some is trapped for cell use and the rest is lost as heat.
The body strives for a balance between anabolic and catabolic processes. However,
there are times when one is more prominent than the other. For example, during growth
there is a net anabolic state because more tissue is being synthesized than broken down.
However, during weight loss or a wasting disease, such as cancer, more tissue is being
broken down than synthesized.
Energy for the Cell
Cells use energy for the following purposes: building compounds, contracting muscles, con-
ducting nerve impulses, and pumping ions (e.g., across cell membranes).1 This energy comes
from catabolic reactions that break the chemical bonds between the atoms in carbohydrate,
fat, protein, and alcohol. This energy is originally produced during photosynthesis, when
plants use solar energy to make glucose and other
Catabolism
organic (carbon-containing) compounds (see
Chapter 5). The chemical reactions in photosyn-
Proteins Carbohydrates Lipids Alcohol
Stage 1 thesis form compounds that contain more energy
Digestion: breakdown 1 than the building blocks used—carbon dioxide
of complex molecules and water. Virtually all organisms use the sun—
to their component either indirectly, as we do, or directly—as their
Amino acids Monosaccharides Fatty acids,
building blocks
glycerol source of energy.1
ATP As shown in Figure 9-2, the series of cata-
Stage 2 2
CO2
bolic reactions that produce energy for body cells
Conversion of building
blocks to acetyl-CoA begins with digestion and continues when mono-
(or other simple Acetyl-CoA saccharides, amino acids, fatty acids, glycerol, and
intermediates) alcohol are sent through a series of metabolic path-
3 ways, which finally trap a portion of the energy
Stage 3
they contain into a compound called adenosine
Metabolism of
acetyl-CoA to CO2 ATP triphosphate (ATP)—the main form of energy
Citric acid
and formation of ATP cycle CO2 the body uses. Heat, carbon dioxide, and water
(and electron also result from these catabolic pathways. The heat
transport chain)
produced helps maintain body temperature. Plants
can use the carbon dioxide and water to produce
Figure 9-2 Three stages of catabolism. glucose and oxygen via photosynthesis.

4. chapter 9 Energy Metabolism 283
Adenosine Triphosphate (ATP)
Only the energy in ATP and related compounds can be used directly by the cell.3 A molecule
of ATP consists of the organic compound adenosine (comprised of the nucleotide adenine
and the sugar ribose) bound to 3 phosphate groups (Fig. 9-3). The bonds between the phos-
phate groups contain energy and are called high-energy phosphate bonds. Hydrolysis of the
high-energy bonds releases this energy. To release the energy in ATP, cells break a high-energy
phosphate bond, which creates adenosine diphosphate (ADP) plus Pi, a free (inorganic)
phosphate group (Fig. 9-4). Hydrolysis of ADP results in the compound adenosine mono-
phosphate (AMP) in a reaction muscles are capable of performing during intense exercise
when ATP is in short supply (ADP + ADP → ATP + AMP). ATP can be regenerated by add-
ing the phosphates back to AMP and ADP.
Figure 9-3 ATP is a storage form of energy
Adenine for cell use because it contains high-energy
bonds. Pi is the abbreviation for an inorganic
phosphate group.
Ribose Pi Pi Pi
Adenosine High-energy
bonds
High-energy bonds Figure 9-4 ATP stores and yields energy. ATP
is the high-energy state; ADP is the lower-energy
P ~P ~P ATP state. When ATP is broken down to ADP plus Pi ,
energy is released for cell use. When energy is
trapped by ADP plus Pi ATP can be formed.
,
Pi
Pi
P ~P ADP
Energy released Energy used
in catabolic in anabolic
pathways pathways
Every cell requires energy from ATP to synthesize new compounds (anabolic path-
ways), to contract muscles, to conduct nerve impulses, and to pump ions across membranes.
Catabolic pathways in cells release energy, which allows ADP to combine with Pi
and form ATP. Every cell has pathways to break down and resynthesize ATP. A
A Biochemist , View
cell is constantly breaking down ATP in one site while rebuilding it in another.
This recycling of ATP is an important strategy because the body contains only
about 0.22 lb (100 g) of ATP at any given time, but a sedentary adult uses about s
88 lb (40 kg) of ATP each day. The requirement increases even more during NH2
exercise—during 1 hour of strenuous exercise, an additional 66 lb (30 kg) of
ATP are used. In fact, the runner who currently holds the American record for N
Adenine N
the men’s marathon was estimated to use 132 lb (65 kg) to run the race.24
High-energy
phosphate bonds N
N
Oxidation-Reduction Reactions: Key Processes
O O O
in Energy Metabolism O
�O
P O P O P O
The synthesis of ATP from ADP and Pi involves the transfer of energy from
energy-yielding compounds (carbohydrate, fat, protein, and alcohol). This pro- O� O� O�
cess uses oxidation-reduction reactions, in which electrons (along with hydrogen OH OH
ions) are transferred in a series of reactions from energy-yielding compounds
eventually to oxygen. These reactions form water and release much energy, Ribose
which can be used to produce ATP.

5. 284 Part 3 Metabolism and Energy Balance
The mnemonic “LeO [loss of electrons is A substance is oxidized when it loses 1 or more electrons. For example, copper is
oxidation] the lion says Ger [gain of electrons oxidized when it loses an electron:
is reduction]” can help you differentiate Cu+ ∆ Cu2+ + e-
between oxidation and reduction. A substance is reduced when it gains 1 or more electrons. For example, iron is re-
duced when it gains an electron:
Fe3+ + e- ∆ Fe2+
, The movement of electrons governs oxidation-reduction processes. If 1 substance loses
A Biochemist s View electrons (is oxidized), another substance must gain electrons (is reduced). These processes
go together; one cannot occur without the other.2 In the previous examples, the electron lost
CH2OH
by copper can be gained by the iron, resulting in this overall reaction;:
Cu+ + Fe3+ → Cu2++ Fe2+
O
H H Oxidation-reduction reactions involving organic (carbon-containing) compounds are
H somewhat more difficult to visualize. Two simple rules help identify whether these com-
OH H pounds are oxidized or reduced:
HO OH If the compound gains oxygen or loses hydrogen, it has been oxidized.
H OH If it loses oxygen or gains hydrogen, the compound has been reduced.
Enzymes control oxidation-reduction reactions in the body. Dehydrogenases, one
Glucose
class of these enzymes, remove hydrogens from energy-yielding compounds or their
O breakdown products. These hydrogens are eventually donated to oxygen to form water.
In the process, large amounts of energy are converted to ATP.1
C O�
Two B-vitamins, niacin and riboflavin, assist dehydrogenase enzymes and, in turn, play
a role in transferring the hydrogens from energy-yielding compounds to oxygen in the meta-
C O
bolic pathways of the cell.2 In the following reaction, niacin functions as the coenzyme nicoti-
CH3 namide adenine dinucleotide (NAD). NAD is found in cells in both its oxidized form (NAD)
and reduced form (NADH). During intense (anaerobic) exercise, the enzyme lactate dehy-
Pyruvate drogenase helps reduce pyruvate (made from glucose) to form lactate. During reduction, 2
hydrogens, derived from NADH + H+, are gained. Lactate is oxidized back to pyruvate by
losing 2 hydrogens. NAD+ is the hydrogen acceptor. That is, the oxidized form of niacin
coenzyme Compound that combines (NAD+) can accept 1 hydrogen ion and 2 electrons to become the reduced form NADH +
with an inactive protein, called an H+. (The plus [+] on NAD+ indicates it has 1 less electron than in its reduced form. The extra
apoenzyme, to form a catalytically hydrogen ion [H+] remains free in the cell.) By accepting 2 electrons and 1 hydrogen ion,
active protein, called a holoenzyme. In NAD+ becomes NADH + H+, with no net charge on the coenzyme.
this manner, coenzymes aid in enzyme
function.
NADH ϩ Hϩ NADϩ
O O OH O
The term antioxidant is typically used
CH3 C C OϪ CH3 C C OϪ
to describe a compound that can donate
electrons to oxidized compounds, putting them Pyruvate
(Oxidized) H
into a more reduced (stable) state. Oxidized NADH ϩ Hϩ NADϩ
compounds tend to be highly reactive; they Lactate
(Reduced)
seek electrons from other compounds to
stabilize their chemical configuration. Dietary Riboflavin plays a similar role. In its oxidized form, the coenzyme form is known as
antioxidants, such as vitamin E, donate flavin adenine dinucleotide (FAD). When it is reduced (gains 2 hydrogens, equivalent to
electrons to these highly reactive compounds, 2 hydrogen ions and 2 electrons), it is known as FADH2.
in turn, putting these oxidized compounds into The reduction of oxygen (O) to form water (H2O) is the ultimate driving force for life be-
a less reactive state (see Chapter 12). cause it is vital to the way cells synthesize ATP. Thus, oxidation-reduction reactions are a key to life.
Knowledge Check
1. What is the main form of energy used by the body?
2. What are catabolic and anabolic reactions?
3. What is the difference between oxidation and reduction reactions?
4. How do niacin and riboflavin play a role in metabolism?

6. CHaPtEr 9 Energy Metabolism 285
9.2 ATP Production from Carbohydrates A new tool for understanding how
individuals differ in the metabolic response
to nutrients may lie in the ability to track the
Cells release energy stored in food fuels and then trap as much of this energy as possible
actual metabolic intermediates made during
in the form of ATP. The body cannot afford to lose all energy immediately as heat, even
metabolism, such as how we respond to
though some heat is necessary for the maintenance of body temperature. This section ex-
exposure to different fatty acids. This approach,
amines how ATP is produced from carbohydrates. Subsequent sections will explore how
called metabolomics, should be more accurate
ATP is produced using the energy stored in fats, proteins, and alcohol. Along the way,
than looking for differences in DNA between
you will see how these energy-yielding processes are interconnected.
individuals to predict dietary responses.
ATP is generated through cellular respiration. The process of cellular respira-
tion oxidizes (removes electrons) food molecules to obtain energy (ATP). Oxygen
is the final electron acceptor. As you know, humans inhale oxygen and exhale carbon
dioxide. When oxygen is readily available, cellular respiration may be aerobic. When
oxygen is not present, anaerobic pathways are used. Aerobic respiration is far more
efficient than anaerobic metabolism at producing ATP. As an example, the aerobic
respiration of a single molecule of glucose will result in a net gain of 30 to 32 ATP.
In contrast, the anaerobic metabolism of a single molecule of glucose is limited to a aerobic Requiring oxygen.
net gain of 2 ATP.
The 4 overall stages of aerobic cellular respiration of glucose are as follows anaerobic Not requiring oxygen.
(Fig. 9-5).1, 4
cytosol Water-based phase of a cell’s
Stage 1: Glycolysis. In this pathway, glucose (a 6-carbon compound) is oxidized and cytoplasm; excludes organelles, such as
forms 2 molecules of the 3-carbon compound pyruvate, produces NADH + H+, and mitochondria.
generates a net of 2 molecules of ATP. Glycolysis occurs in the cytosol of cells.
Figure 9-5 The 4 phases of aerobic carbohydrate metabolism. Glycolysis in the cytoplasm produces
pyruvate (stage 1 ), which enters mitochondria if oxygen is available. The transition reaction (stage 2 ), citric
acid cycle (stage 3 ), and electron transport chain (stage 4 ) occur inside the mitochondria. The electron
transport chain receives the electrons that were removed from glucose breakdown products during stages 1
through 3. The result of aerobic glucose breakdown is 30 to 32 ATP depending on the particular cell.
,
e�
4
NADH � H�
Electron transport chain
e� 3O2 � 12H� 6H2O
NADH � H�
e� NADH � H�
and FADH2
1
2
Transition
Glycolysis reaction 3
Acetyl- Citric acid
Glucose 2 Pyruvate CoA cycle
2 CO2 2 CO2
26 or
2 ADP 2 ADP 28 ADP
2 ATP 2 ATP 26 or
28 ATP

7. 286 Part 3 Metabolism and Energy Balance
Stage 2: Synthesis of acetyl-CoA. In this stage, pyruvate is further oxidized and joined
mitochondria Main sites of energy with coenzyme A (CoA) to form acetyl-CoA. The transition reaction also produces
production in a cell. They also contain NADH + H+ and releases carbon dioxide (CO2) as a waste product. The transition
the pathway for oxidizing fat for fuel, reaction takes place in the mitochondria of cells.
among other metabolic pathways.
Stage 3: Citric acid cycle. In this pathway, acetyl-CoA enters the citric acid cycle, result-
ing in the production of NADH + H+, FADH2, and ATP. Carbon dioxide is released
A number of defects are related to as a waste product. Like the transition reaction, the citric acid cycle takes place within
the metabolic processes that take place the mitochondria of cells.
in mitochondria. A variety of medical
Stage 4: Electron transport chain. The NADH + H+ produced by stages 1 through 3
interventions, some of which use
of cellular respiration and FADH2 produced in stage 3 enter the electron transport
specific nutrients and related metabolic
chain, where NADH + H+ is oxidized to NAD+, and FADH2 is oxidized to FAD. At
intermediates, can be used to treat the
the end of the electron transport chain, oxygen is combined with hydrogen ions (H+)
muscle weakness and muscle destruction
and electrons to form water. The electron transport chain takes place within the mi-
typically arising from these disorders.
tochondria of cells. Most ATP is produced in the electron transport chain; thus, the
mitochondria are the cell’s major energy-producing organelles.
acetyl-coa
O
O Glycolysis
Because glucose is the main carbohydrate involved in cell metabolism, we will track its
CoA – S
CoA – S CH 33
CH step-by-step metabolism as an example of carbohydrate metabolism. Glucose metabolism
begins with glycolysis, which means “breaking down glucose.” Glycolysis has 2 roles:
CoA is short for coenzyme A. The A stands for to break down carbohydrates to generate energy and to provide building blocks for syn-
acetylation because CoA provides the 2-carbon thesizing other needed compounds. During glycolysis, glucose passes through several
acetyl group to start the citric acid cycle. steps, which convert it to 2 units of a 3-carbon compound called pyruvate. The details of
glycolysis can be found in Figure 9-6.
Synthesis of Acetyl-CoA
Pyruvate passes from the cytosol into the mitochondria, where the enzyme pyruvate
Pyruvate dehydrogenase converts pyruvate into the compound acetyl-CoA in a process called a tran-
CO2
sition reaction5 (Fig. 9-7). This overall reaction is irreversible, which has important met-
NAD� abolic consequences. Whereas glycolysis requires only the B-vitamin niacin as NAD, the
CoA conversion of pyruvate to acetyl-CoA requires coenzymes from 4 B-vitamins—thiamin,
riboflavin, niacin, and pantothenic acid. In fact, CoA is made from the B-vitamin pantoth-
NADH � H� enic acid. For this reason, carbohydrate metabolism depends on an ample supply of these
Acetyl-CoA vitamins (see Chapter 13).2
The transition reaction oxidizes pyruvate and reduces NAD+. Each glucose yields
Figure 9-6 Pyruvate dehydrogenase assists 2 acetyl-CoA. As with the NADH + H+ produced by glycolysis, the 2 NADH + 2 H+
in the transition reaction where pyruvate is
metabolized to acetyl-CoA. It is acetyl-CoA that
produced by the transition reaction will eventually enter the electron transport chain.
actually enters the citric acid cycle. In the process, Carbon dioxide is a waste product of the transition reaction and is eventually eliminated
NADH + H+ is produced and CO2 is lost. by way of the lungs.
Knowledge Check
1. What is the first step to bring glucose into the cell to start glycolysis?
2. How many 3-carbon compounds are made from a 6-carbon glucose
molecule?
3. What is the end product of glycolysis?
4. What nutrients are involved in the transition reaction?

8. chapter 9 Energy Metabolism 287
Glucose
ATP ~ ~ The first step of glycolysis is to activate the glucose molecule by attaching
1 1
ADP ~ a phosphate group to it. The attached phosphate group is supplied by
ATP, which means that energy is required for this step and that ADP is
formed.
Glucose
6-phosphate
Fructose
6-phosphate
ATP ~ ~ The molecule is rearranged and a second phosphate group is added
2 2
ADP ~ using ATP, forming fructose 1,6-bisphosphate. Again, ATP provides the
phosphate, making this an energy-requiring step.
Fructose
1,6-bisphosphate 3 Fructose 1,6-biphosphate is split in half to form two 3-carbon molecules,
each of which has 1 phosphate—glyceraldehyde 3-phosphate and
dihydroxyacetone phosphate. Dihydroxyacetone phosphate is eventually
converted into glyceraldehyde 3-phosphate. Thus, step 4 onward
Glyceraldehyde Dihydroxyacetone occurs twice for each molecule of glucose that enters glycolysis.
3-phosphate 3 phosphate
NAD�
4 4 A dehydrogenase enzyme oxidizes each of the two 3-carbon molecules.
NADH � H� NAD is reduced, forming 2NADH � 2H�. A phosphate molecule is
added to each 3-carbon molecule.
1,3-bisphospho-
glycerate ~
ADP ~ 5 5 An enzyme transfers 1 phosphate from each of the 3-carbon molecules to
an ADP, forming 2 ATP. This is the first synthesis of the high-energy
ATP ~ ~ compound ATP in the pathway.
3-phospho-
glycerate
6 6 Water is removed from each of the 3-carbon molecules, which produces
H2O two 3-carbon-phosphate molecules.
Phospho-
~
enolpyruvate
ADP ~ An enzyme transfers 1 phosphate from each of the 3-carbon molecules to
7 7
ATP ~ ~ an ADP, thereby producing a total of 2 ATP.
Pyruvate 8 8 The last step in glycolysis is the formation of pyruvate. Generally, pyruvate
enters the mitochondria for further metabolism. A total of 2 pyruvates are
formed from each glucose that enters glycolysis.
Carbon
Phosphate group
Adenosine
Figure 9-7 Glycolysis takes place in the cytosol portion of the cell. This process breaks glucose (a 6-carbon compound) into 2 units of a 3-carbon compound
called pyruvate. More details can be found in Appendix A.

9. 288 Part 3 Metabolism and Energy Balance
, Citric Acid Cycle
A Biochemist s View The acetyl-CoA molecules produced by the transition reaction enter the citric acid cycle,
O O which also is known as the tricarboxylic acid cycle (TCA cycle) and the Krebs cycle. The
citric acid cycle is a series of chemical reactions that cells use to convert the carbons of an
C C O� acetyl group to carbon dioxide while harvesting energy to produce ATP.3
O It takes 2 turns of the citric acid cycle to process 1 glucose molecule because glycolysis and
the transition reaction yield 2 acetyl-CoA. Each complete turn of the citric acid cycle produces
CH2 C O� 2 molecules of CO2 and 1 potential ATP in the form of 1 molecule of guanosine triphosphate
Oxaloacetate
(GTP), as well as 3 molecules of NADH + H+ and 1 molecule of FADH2. Oxygen does not
participate in any of the steps in the citric acid cycle; however, it does participate in the electron
O
transport chain. The details of the citric acid cycle can be found in Figure 9-8; further details are
in Appendix A.
CH2 C O�
O
HO C C O� Pyruvate
O
NAD� Transition step:
CH2 C O� Oxidation generates
CoA NADH � H� NADH, CO2 is removed,
Citrate (Citric Acid) and coenzyme A is added.
CO2
1 To begin the citric acid cycle, the 2-carbon compound acetyl-
Acetyl-CoA CoA combines with a 4-carbon compound, oxaloacetate, to
CoA form the 6-carbon compound citrate. In the process, the
corresponding CoA molecule is released and can be reused.
NADH � H� Oxaloacetate
Citrate NAD� 2 The 6-carbon citrate is oxidized
(hydrogen removed), forming
the 5-carbon compound alpha-
5 The 4-carbon fumarate is NADH � H�
NAD� ketoglutarate, NADH � H�,
oxidized, forming the 4-carbon
and CO2.
compound oxaloacetate—the
compound used to begin the
citric acid cycle (step 1)—and CO2
NADH � H�.
H2O
�-ketoglutarate
Fumarate
4 The 4-carbon succinate is NAD�
oxidized to the 4-carbon
FADH2 compound fumarate.
FADH2 is formed.
NADH � H�
3 The 5-carbon alpha-ketoglutarate
FAD CO2 is oxidized, forming the 4-carbon
Succinate compound succinate, NADH �
H�, CO2, and guanosine
triphosphate (GTP), which is
GDP ~
converted to ATP.
GTP ~ ~
Figure 9-8 How the citric acid cycle works. During ATP ~ ~
1 complete turn of the citric acid cycle, the 6-carbon
citrate molecule is converted to a 4-carbon oxaloacetate
molecule. The cycle is now ready to begin again with the
regenerated oxaloacetate and another acetyl-CoA. See
Figure A-2 in Appendix A for a more detailed view of the
citric acid cycle. ADP ~

10. chaPter 9 Energy Metabolism 289
Electron Transport Chain Intermediates of the citric acid cycle, such
as oxaloacetate, can leave the cycle and go
The final pathway of aerobic respiration is the electron transport chain located in the on to form other compounds, such as glucose.
mitochondria. The electron transport chain functions in most cells in the body. Cells Thus, the citric acid cycle should be viewed as a
that need a lot of ATP, such as muscle cells, have thousands of mitochondria, whereas traffic circle, rather than as a closed circle.
cells that need very little ATP, such as adipose cells, have fewer mitochondria. Almost
90% of the ATP produced from the catabolism of glucose is produced by the electron
transport chain.
The electron transport chain involves the passage of electrons along a series of
electron carriers. As electrons are passed from one carrier to the next, small amounts How many ATP are produced by
of energy are released. NADH + H+ and FADH2, produced by glycolysis, the transi- 1 molecule of glucose? The metabolism
tion reaction, and the citric acid cycle, supply both hydrogen ions and electrons to the of 1 glucose molecule yields
electron transport chain. The metabolic process, called oxidative phosphorylation, Glycolysis 2 NADH and 2 ATP
is the way in which energy derived from the NADH + H+ and FADH2 is transferred
Transition reaction 2 NADH
to ADP + Pi to form ATP (Fig. 9-9). Oxidative phosphorylation requires the minerals
copper and iron. Copper is a component of an enzyme, whereas iron is a component Citric acid cycle 6 NADH, 2 FADH2,
of cytochromes (electron-transfer compound) in the electron transport chain. In ad- and 2 GTP
dition to ATP production, hydrogen ions, electrons, and oxygen combine to form total 10 NaDh,
water. The details of the electron transport chain are presented in Figure 9-10. 2 FaDh2,
2 GtP, and 2 atP
High-energy Low-energy
molecule, molecule, such as The NADH and FADH2 generated undergo
such as glucose CO2 and H2O
H� oxidative phosphorylation in the electron
H� transport chain to yield
e�
NADH � H�
e� 2.5 ATP molecules per NADH
or FADH2 1.5 ATP molecules per FADH2
NAD� Thus, 28 ATP molecules are synthesized in
the electron transport chain.
or FAD e� total atP Produced from each Glucose
H� Molecule
e� H�
Pi ATP Glycolysis ATP 2 ATP
ADP �
1
—O
2 2
Citric acid cycle GTP 2 ATP
H2O
Citric acid cycle ATP 28 ATP
total 32 atP
Figure 9-9 Simplified depiction of electron transfer in energy metabolism. High-energy compounds,
such as glucose, give up electrons and hydrogen ions to NAD and FAD. The NADH + H and FADH2 that are
+ +
formed transfer these electrons and hydrogen ions, using specialized electron carriers, to oxygen to form
water (H2O). The energy yielded by the entire process is used to generate ATP from ADP and Pi.
The Importance of Oxygen
NADH + H+ and FADH2 produced during the citric acid cycle can be regenerated into Coenzyme Q-10 is sold as a nutrient
NAD+ and FAD only by the eventual transfer of their electrons and hydrogen ions to supplement in health food stores (10 signifies
oxygen, as occurs in the electron transport chain. The citric acid cycle has no ability that it is the form found in humans). However,
to oxidize NADH + H+ and FADH2 back to NAD+ and FAD. This is ultimately why when the mitochondria need coenzyme Q,
oxygen is essential to many life forms—it is a final acceptor of the electrons and hydro- they make it. Thus, to maintain overall health,
gen ions generated from the breakdown of energy-yielding nutrients. Without oxygen, coenzyme Q is not needed in the diet or as
most of our cells are unable to extract enough energy from energy-yielding nutrients a supplement. (Such use may be helpful,
to sustain life.1 however, in people with heart failure.)

11. 290 Part 3 Metabolism and Energy Balance
Cytosol
Outer
membrane
ATP
Outer H� H� H� H� ATP Carrier
compartment 2 e� 2 synthase ADP molecule
Pi
Inner I II III 2 e� IV
membrane
Inner
compartment 2 e�
2 e� Pi � ADP
2 e�
NADH H� 1 FADH2 H� H�
ATP
2 e�
2 H� H� 4
NAD� H2O 1 3
2 O2
1 2 3 4
NADH � H� and FADH2 transfer Pairs of electrons are then As hydrogen ions diffuse One carrier molecule
their hydrogen ions and electrons to separated by coenzyme Q back into the inner moves ADP into the inner
the electron carriers located on the (CoQ) and each electron is compartment through compartment and a
inner mitochondrial membrane. then passed along a group special channels, ATP is different carrier molecule
Although NADH � H� and FADH2 of iron-containing produced by the enzyme moves phosphate (Pi) into
transfer their hydrogens to the electron cytochromes. At each ATP synthase. At the end of the inner compartment. In
transport chain, the hydrogen ions transfer from one the chain of cytochromes, the inner compartment, the
(H�), having been separated from cytochrome to the next, the electrons, hydrogen energy generated by the
their electron (H H� � e�), are not energy is released. Some ions, and oxygen combine electron transport chain
carried down the chain with the of this energy is used to to form water. Oxygen is unites ADP to Pi to form
electrons. Instead, the hydrogen ions pump hydrogen ions into the final electron acceptor ATP. ATP is transported out
are pumped into the outer the outer compartment. A and is reduced to form of the inner compartment
compartment (located between the portion of the energy is water. by a carrier protein
inner and outer membrane of a eventually used to generate molecule that exchanges
mitochondrion). The NAD� and FAD ATP from ADP and Pi, but ATP for ADP.
regenerated from the oxidation of the much is simply released as
NADH � H� and FADH2 are now heat.
ready to function in glycolysis, the
transition reaction, and the citric acid
cycle.
Figure 9-10 The electron transport chain.
In Figure 9-10, step 1, NADH + H+ donates
its chemical energy to an FAD-related Anaerobic Metabolism
compound called flavin mononucleotide
(FMN). In contrast, FADH2 donates its chemical Some cells lack mitochondria and, so, are not capable of aerobic respiration. Other cells
energy at a later point in the electron transport are capable of turning to anaerobic metabolism when oxygen is lacking. When oxygen is
chain. This different placement of FAD and absent, pyruvate that is produced through glycolysis is converted into lactate, or lactic acid.
NAD+ in the electron transport chain results in Anaerobic metabolism is not nearly as efficient as aerobic respiration because it converts
a difference in ATP production. Each NADH + H+ only about 5% of the energy in a molecule of glucose to energy stored in the high-energy
in a mitochondrion releases enough energy to phosphate bonds of ATP.1
form the equivalent of 2.5 ATP, whereas each The anaerobic glycolysis pathway encompasses glycolysis and the conversion of
FADH2 releases enough energy to form the pyruvate to lactate (Fig. 9-11). The 1-step reaction, catalyzed by the enzyme pyruvate
equivalent of 1.5 ATP.1 dehydrogenase, involves a simple transfer of a hydrogen from NADH + H+ to pyruvate

12. chaPter 9 Energy Metabolism 291
to form lactate and NAD+. The synthesis of lactate In anaerobic environments, some
regenerates the NAD+ required for the continued microorganisms, such as yeast, produce
function of glycolysis. The reaction can be sum- ethanol, a type of alcohol, instead of lactate
marized as from glucose. Other microorganisms produce
various forms of short-chain fatty acids. All
Pyruvate + NADH + H+ → Lactate + NAD+ this anaerobic metabolism is referred to as
fermentation.
For cells that lack mitochondria, such as red
blood cells, anaerobic glycolysis is the only meth-
od for making ATP because they lack the electron
transport chain and oxidative phosphorylation. Glucose
Therefore, when red blood cells convert glucose
to pyruvate, NADH + H+ builds up in the cell. 2 ATP
Eventually, the NAD+ concentration falls too low
to permit glycolysis to continue.5 The anaerobic 2 ADP
glycolysis pathway produces lactate to regener-
ate NAD+. The lactate produced by the red blood 2X P
Glyceraldehyde 3–phosphate
cell is then released into the bloodstream, picked
up primarily by the liver, and used to synthesize
Quick bursts of activity rely on the
production of lactate to help meet the ATP
pyruvate, glucose, or some other intermediate in 2 NAD�
energy demand. aerobic respiration.
Even though muscles cells contain mito- 2 NADH � H�
chondria, during intensive exercise they also produce lactate when NAD+ is depleted. By
regenerating NAD+, the production of lactate allows anaerobic glycolysis to continue. 2X P~ P
1,3–bisphosphoglycerate
Muscle cells can then make the ATP required for muscle contraction even if little oxygen
is present. However, as you will find out in Chapter 11, it becomes more difficult to con-
tract those muscles as the lactate concentration builds up. 2 ADP
2 ATP
Knowledge Check
1. How is citric acid in the citric acid cycle formed? 2X
Pyruvate
2. How many NADH + H+ are formed in the citric acid cycle?
3. Why is the citric acid cycle called a cycle?
4. What is the purpose of the electron transport chain?
5. What are the end products of the electron transport chain? 2X
Lactate
Figure 9-11 Anaerobic glycolysis “frees”
NAD+ and it returns to the glycolysis pathway to
pick up more hydrogen ions and electrons.
C A S E ST U DY
Melissa is a 45-year-old woman who is obese. ketones. In the book, the author states that anyone going on this
At her last physical, her doctor told her that she diet should purchase ketone strips to dip in his or her urine for the
needs to lose weight. Melissa purchased a low- detection of ketones. The author strongly suggests these tests,
carbohydrate, high-protein diet book and has read especially during the extremely low-carbohydrate part of the
it and is now ready to try the diet. She knows it diet. Melissa wonders if she should be considering this diet if the
will be difficult to follow because many of the author is telling her to check something and she wonders what
foods Melissa likes are rich in carbohydrates, and ketones are.
the first 2 weeks of the diet eliminates almost What are ketones and why does a very-low-carbohydrate diet
all carbohydrates from her diet. Although she produce an increase in ketones in both the blood and the urine? Can
is ready to try the diet, she is confused about certain phases of you speculate at this time why low carbohydrates cause ketones? Why
the program, especially the part where the author talks about do some fad diets produce ketones?

13. 292 Part 3 Metabolism and Energy Balance
9.3 ATP Production from Fats
Carnitine is a popular nutritional Just as cells release the energy in carbohydrates and trap it as ATP, they also release and
supplement. In healthy people, cells trap energy in triglyceride molecules. This process begins with lipolysis, the breaking
produce the carnitine needed, and carnitine down of triglycerides into free fatty acids and glycerol. The further breakdown of fatty ac-
supplements provide no benefit. In patients ids for energy production is called fatty acid oxidation because the donation of electrons
hospitalized with acute illnesses, however, from fatty acids to oxygen is the net reaction in the ATP-yielding process. This process
carnitine synthesis may be inadequate. These takes place in the mitochondria.
patients may need to have carnitine added Fatty acids for oxidation can come from either dietary fat or fat stored in the body
to their intravenous feeding (total parenteral as adipose tissue. Following high-fat meals, the body stores excess fat in adipose tissue.
nutrition) solutions. However, during periods of low calorie intake or fasting, triglycerides from fat cells are
broken down into fatty acids by an enzyme called hormone-sensitive lipase and released in
the blood. The activity of this enzyme is increased by hormones such as glucagon, growth
hormone, and epinephrine and is decreased by the hormone insulin. The fatty acids are
taken up from the bloodstream by cells throughout the body and are shuttled from the cell
cytosol into the mitochondria using a carrier called carnitine (Fig. 9-12).6
Figure 9-12 Lipolysis. Because of the action GI Tract
of hormone-sensitive lipase, fatty acids are
released from triglycerides in adipose cells and Dietary
enter the bloodstream. The fatty acids are taken fat
up from the bloodstream by various cells and
shuttled by carnitine into the inner portion of the
cell mitochondria. The fatty acid then undergoes
beta-oxidation, which yields acetate molecules Glycerol Fatty acids
equal in number to half of the carbons in the
fatty acid.
Adipose tissue
Cell
Triglycerides
Hormone- Beta-oxidation
sensitive Acetyl
Fatty acids Carnitine Fatty acids
lipase molecules
Glycerol Fatty acids Mitochondria
Cytosol
Bloodstream
ATP Production from Fatty Acids
Almost all fatty acids in nature are composed of an even number of carbons, ranging from
2 to 26. The first step in transferring the energy in such a fatty acid to ATP is to cleave the
carbons, 2 at a time, and convert the 2-carbon fragments to acetyl-CoA. The process of
converting a free fatty acid to multiple acetyl-CoA molecules is called beta-oxidation be-
cause it begins with the beta carbon, the second carbon on a fatty acid (counting after the
carboxyl [acid] end).1 (See Chapter 6.) During beta-oxidation, NADH + H+ and FADH2
are produced (Fig. 9-13). Thus, as with glucose, a fatty acid is eventually degraded into a
number of the 2-carbon compound acetyl-CoA (the exact number produced depends on
the number of carbons in the fatty acid). Some of the chemical energy contained in the fatty
acid is transferred to NADH + H+ and FADH2.

14. chapter 9 Energy Metabolism 293
H
Figure 9-13 In beta-oxidation, each 2-carbon
H H H H H H O
fragment cleaved from a fatty acid (acetyl group)
yields electrons and hydrogen ions to form NADH
H C C C C C C C C OH + H+ and FADH2 as the fragments are split off the
parent fatty acid. The 2-carbon acetyl molecule
H H H H H H H then typically enters the citric acid cycle (as
acetyl-CoA).
NADH � H� Beta-carbon
FADH2
H H H H H H H O
H C C C C C C C C OH
H H H H H H H
NADH � H� NADH � H�
FADH2 FADH2
H H H H H H H O
H C C C C C C C C OH
H H H H H H H
NADH � H� NADH � H� NADH � H�
Glucose
FADH2 FADH2 FADH2
P
~
The acetyl-CoA enters the citric acid cycle, and 2 carbon dioxides are re- Phosphoenolpyruvate
leased, just as with the acetyl-CoA produced from glucose. Thus, the breakdown
product of both glucose and fatty acids—acetyl-CoA—enter the citric acid cy-
cle. One big difference, however, is that a 16-carbon fatty acid yields 104 ATP,
whereas the 6-carbon glucose yields only 30 to 32 ATP. The difference in ATP
production occurs because each 2-carbon segment in the fatty acid goes around Pyruvate
Fatty acids
the citric acid cycle; thus, a 16-carbon fatty acid goes around the citric acid cycle from beta-
oxidation
8 times. Additionally, each fatty acid carbon results in about 7 ATP, whereas about
5 ATP per carbon result from glucose oxidation. This is because fatty acids have
CoA
~
more carbon-hydrogen bonds and fewer carbon-oxygen atoms than glucose. The
carbons of glucose exist in a more oxidized state than fat; as a result, fats yield more Acetyl-CoA
energy than carbohydrates (9 kcal/g versus 4 kcal/g).1
Occasionally, a fatty acid has an odd number of carbons, so the cell forms a 3-car-
bon compound (propionyl-CoA) in addition to the acetyl-CoA. The propionyl-CoA en-
ters the citric acid cycle directly, bypassing acetyl-CoA. It can then go on to yield NADH
Oxaloacetate Citrate
+ H+ and FADH2, CO2, and even other products, such as glucose (see Section 9.4).
Citric acid
cycle
Carbohydrate Aids Fat Metabolism
In addition to its role in energy production, the citric acid cycle provides compounds
that leave the cycle and enter biosynthetic pathways. This results in a slowing of the
cycle, as eventually not enough oxaloacetate is formed to combine with the acetyl- Figure 9-14 As acetyl-CoA concentrations
increase due to beta-oxidation, oxaloacetate
CoA entering the cycle. Cells are able to compensate for this by synthesizing addi- levels are maintained by pyruvate from
tional oxaloacetate. One potential source of this additional oxaloacetate is pyruvate carbohydrate metabolism. In this way,
(Fig. 9-14). Thus, as fatty acids create acetyl-CoA, carbohydrates (e.g., glucose) are carbohydrates help oxidize fatty acids.

15. 294 Part 3 Metabolism and Energy Balance
, needed to keep the concentration of pyruvate high enough to resupply oxaloacetate
A Biochemist s View to the citric acid cycle. Overall, the entire pathway for fatty acid oxidation works
better when carbohydrate is available.
O O
CH3 C C O� Ketogenesis
Pyruvate Ketone bodies are products of incomplete fatty acid oxidation.7 This occurs mainly
CO2 with hormonal imbalances—chiefly, inadequate insulin production to balance glucagon
action in the body. These imbalances lead to a significant production of ketone bodies
and a condition called ketosis. The key steps in the development of ketosis are shown
O O in Figure 9-15.
Most ketone bodies are subsequently converted back into acetyl-CoA in other body
C C O� cells, where they then enter the citric acid cycle and can be used for fuel. One of the ketone
O bodies formed (acetone) leaves the body via the lungs, giving the breath of a person in
ketosis a characteristic, fruity smell.
CH2 C O�
Oxaloacetate
Ketosis in Diabetes
In type 1 diabetes, little to no insulin is produced. This lack of insulin does not allow for
ketone bodies Incomplete breakdown normal carbohydrate and fat metabolism. Without sufficient insulin, cells cannot readily
products of fat, containing 3 or 4 utilize glucose, resulting in rapid lipolysis and the excess production of ketone bodies.8
carbons. Most contain a chemical If the concentration of ketone bodies rises too high in the blood, the excess spills into
group called a ketone. An example is the urine, pulling the electrolytes sodium and potassium with it. Eventually, severe ion
acetoacetic acid. imbalances occur in the body. The blood also becomes more acidic because 2 of the 3
ketosis Condition of having a high
concentration of ketone bodies and
related breakdown products in the Stage 1
bloodstream and tissues.
1 Insufficient insulin production Blood insulin drops, usually as a result of
type 1 diabetes or low carbohydrate
intake.
Stage 2
Large amounts of fatty acids
2 released by adipose cells A fall in blood insulin promotes lipolysis,
which causes fatty acids stored in adipose
cells to be released rapidly into the
bloodstream.
Fatty acids flood into the liver and are
3 broken down into acetyl-CoA. Stage 3
Most of the fatty acids in the blood are
taken up by the liver.
Stage 4
Acetyl-CoA Ketone bodies As the liver oxidizes the fatty acids to
acetyl-CoA, the capacity of the citric acid
O O cycle to process the acetyl-CoA molecules
decreases. This is mostly because the
metabolism of fatty acids to acetyl-CoA
5 CH3 C CH2 C OH yields many ATP. When the cells have
Citric acid plenty of ATP, there is no need to use the
cycle High amounts of acetyl- citric acid cycle to produce more.
CoA unite in pairs to form
4 ketone bodies, such as Stage 5
acetoacetic acid.
High amounts of ATP These metabolic changes encourage liver
slow the processing cells to combine a 2 acetyl-CoA molecules
of acetyl-CoA to ATP. to form a 4-carbon compound. This
compound is further metabolized and
eventually secreted into the bloodstream
Figure 9-15 Key steps in ketosis. Any as ketone bodies (acetoacetic acid and
condition that limits insulin availability to cells the related compounds, beta-
results in some ketone body production. hydroxybutyric acid and acetone).

16. chaPter 9 Energy Metabolism 295
forms of ketone bodies contain acid groups. The resulting condition, known as diabetic
ketoacidosis, can induce coma or death if not treated immediately, such as with insulin, CRITICAL THINKING
electrolytes, and fluids (see Chapter 5). Ketoacidosis usually occurs only in ketosis caused
The use of a very low carbohydrate
by uncontrolled type 1 diabetes; in fasting, blood concentrations of ketone bodies typi-
diet to induce ketosis for weight loss is
cally do not rise high enough to cause the problem.
covered in Chapter 10. Why is careful
physician monitoring needed if this type
of diet is followed?
Ketosis in Semistarvation or Fasting
When a person is in a state of semistarvation or fasting, the amount of glucose in the body
falls, so insulin production falls. This fall in blood insulin then causes fatty acids to flood
into the bloodstream and eventually form ketone bodies in the liver. The heart, muscles,
and some parts of the kidneys then use ketone bodies for fuel. After a few days of ketosis,
the brain also begins to metabolize ketone bodies for energy.
This adaptive response is important to semistarvation or fasting. As more body cells
begin to use ketone bodies for fuel, the need for glucose as a body fuel diminishes. This
then reduces the need for the liver and kidneys to produce glucose from amino acids
(and from the glycerol released from lipolysis), sparing much body protein from being
used as a fuel source (see Section 9.4). The maintenance of body protein mass is a key to
survival in semistarvation or fasting—death occurs when about half of the body protein
is depleted, usually after about 50 to 70 days of total fasting.9
Knowledge Check
1. What is anaerobic glycolysis?
2. What cells use anaerobic glycolysis?
3. How do fatty acids enter the citric acid cycle?
4. What conditions must exist in the body to promote the formation of
ketones?
9.4 Protein Metabolism
The metabolism of protein (i.e., amino acids) takes place primarily in the liver. Only
branched-chain amino acids—leucine, isoleucine, and valine—are metabolized mostly at
other sites—in this case, the muscles.2
Metabolism is part of everyday life; metabolic
Protein metabolism begins after proteins are degraded into amino acids. To use activity increases when we increase physical activity
an amino acid for fuel, cells must first deaminate them (remove the amino group) (see and slows during fasting and semi-starvation.
Chapter 7). These pathways often require vitamin B-6 to function. Removal of the amino
group produces carbon skeletons, most of which enter the citric acid cycle. Some carbon
skeletons also yield acetyl-CoA or pyruvate.5
Some carbon skeletons enter the citric acid cycle as acetyl-CoA, whereas others
form intermediates of the citric acid cycle or glycolysis (Fig. 9-16). Any part of the carbon
skeleton that can form pyruvate (i.e., alanine, glycine, cysteine, serine, and threonine)
or bypass acetyl-CoA and enter the citric acid cycle directly (such amino acids include
asparagine, arginine, aspartic acid, histidine, glutamic acid, glutamine, isoleucine, me-
thionine, proline, valine, and phenylalanine) are called glucogenic amino acids because
these carbons can become the carbons of glucose. Any parts of carbon skeletons that
become acetyl-CoA (leucine and lysine, as well as parts of isoleucine, phenylalanine, tryp- Branched-chain amino acids are added to
tophan, and tyrosine) are called ketogenic amino acids because these carbons cannot some liquid meal replacement supplements
become parts of glucose molecules. The factor that determines whether an amino acid is given to hospitalized patients. Some fluid
glucogenic or ketogenic is whether part or all of the carbon skeleton of the amino acid replacement formulas marketed to athletes
can yield a “new” oxaloacetate molecule during metabolism, 2 of which are needed to also contain branched-chain amino acids (see
form glucose. Chapter 11).

17. 296 Part 3 Metabolism and Energy Balance
Figure 9-16 Gluconeogenesis. Amino acids
that can yield glucose can be converted to Glucose
pyruvate 1 , directly enter the citric acid cycle 3 ,
or be converted directly to oxaloacetate 2X 2X
4 . Amino acids that cannot yield glucose are
converted to acetyl Co-A and are metabolized in
the citric acid cycle 2 . The glycerol portion of Glyceraldehyde Glycerol 5
triglycerides 5 can be converted to glucose. All 3-phosphate
amino acids except ketogenic amino acids can be
used to make glucose. Fatty acids with an even
number of carbons and ketogenic amino acids
cannot become glucose 2 .
~
Phosphoenolpyruvate
(PEP)
Glucogenic amino acids, such as
alanine, glycine, cysteine, serine, and
threonine 1
Pyruvate
Fatty acids
CoA
~
Acetyl-CoA Ketogenic amino acids, such as leucine
4 and lysine, and parts of isoleucine, 2
phenylalanine, tryptophan, and tyrosine
Oxaloacetate
Citric acid
cycle Glucogenic amino acids, such as
asparagine, arginine, aspartic acid,
histidine, glutamic acid, glutamine, 3
gluconeogenesis Generation (genesis) isoleucine, methionine, proline, valine,
of new (neo) glucose from certain and phenylalanine
(glucogenic) amino acids. Glucogenic amino acids,
such as alanine,
isoleucine, phenylalanine,
threonine, methionine,
tyrosine, and aspartate
,
A Biochemist s View
NH3 Gluconeogenesis: Producing Glucose from Glucogenic Amino
CH3 CH O Acids and Other Compounds
C OH The pathway to produce glucose from certain amino acids—gluconeogenesis—is pres-
Alanine ent only in liver cells and certain kidney cells. The liver is the primary gluconeogenic or-
gan. A typical starting material for this process is oxaloacetate, which is derived primarily
CO2
from the carbon skeletons of some amino acids, usually the amino acid alanine. Pyruvate
NH3
also can be converted to oxaloacetate (see Fig. 9-14).
Gluconeogenesis begins in the mitochondria with the production of oxaloacetate.
The 4-carbon oxaloacetate eventually returns to the cytosol, where it loses 1 carbon di-
O O O oxide, forming the 3-carbon compound phosphoenolpyruvate, which then reverses the
path back through glycolysis to glucose. It takes 2 of this 3-carbon compound to produce
�O C C CH2 C O�
the 6-carbon glucose. This entire process requires ATP, as well as coenzyme forms of the
Oxaloacetate B-vitamins biotin, riboflavin, niacin, and B-6.5