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Focus on Metabolism
CHAPTER OUTLINE
FOCUS 6.1
The Chemistry of Life
Molecules
Chemical Reactions
FOCUS 6.2
Metabolic Pathways
Catabolic Pathways
Anabolic Pathways
Energy-Yielding Nutrients and Energy
Balance
The Role of Micronutrients
in Metabolism
FOCUS 6.3
Breaking Down Nutrients
to Provide Energy
Cellular Respiration: Glucose Catabolism
Breaking Down Triglycerides for Energy
Using Amino Acids for Energy
FOCUS 6.4
The Metabolism of Feasting
and Fasting
The Fed State
The Fasted State
F6.1
atom The smallest unit of an
element that still retains the
properties of that element.
ion An atom or molecule that
has a positive or negative charge
because it has unequal numbers
of protons and electrons.
molecule A group of two or
more atoms of the same or different elements bonded together.
The Chemistry of Life
All matter on Earth is made of units called atoms. Atoms
of different elements have different characteristics. Carbon,
hydrogen, oxygen, and nitrogen are the most abundant elements in our bodies and in the foods we eat. The atoms of each element have a characteristic way of losing, gaining, or sharing their electrons when interacting with other atoms
to achieve stability. The way that electrons behave enables atoms in the body to exist in
electrically charged forms called ions or to join with each other into complex combinations called molecules. The chemistry of all life on Earth is based on organic molecules,
which are those that contain carbon bonded to hydrogen. Water is an inorganic molecule
because it does not contain carbon-hydrogen bonds.
2
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Figure F6.1
organic molecule A molecule
that contains carbon bonded to
hydrogen.
Chemical bonds
Na
Na
Electron
donated
Sodium Atom
inorganic molecule A molecule
that contains no carbon-hydrogen
bonds.
Sodium Ion
Cl
Na
Electron
accepted
Sodium chloride
Cl
Cl
Chloride Atom
Chloride Ion
(a) If an atom or molecule either gives up an electron, as shown by the sodium (Na) atom, or gains an
electron, as shown by the chloride (Cl) atom, it becomes an ion. An ionic bond is formed when the electrical
charges attract the ions to each other, in this case forming sodium chloride (NaCl), or table salt.
+
H
Hydrogen atoms
H
H
FOCUS ON Metabolism
F 6 .1 The Chemistry of Life 3
metabolic pathway A series
of chemical reactions inside a
living organism that results in the
transformation of one molecule
into another.
H
Hydrogen molecule
Sugar
(b) Covalent bonds form when two atoms share electrons. In this example, two hydrogen (H) atoms share
an electron, forming a hydrogen molecule (H2).
Molecules
The forces that link atoms together are called chemical bonds (Figure F6.1). With
the exception of minerals, which are individual elements, all of the nutrients we
consume are molecules. Most biological molecules are very large and are built
by assembling small molecules, or monomers, into long chains, called polymers
(Figure F6.2). Polymers are formed by chemical reactions called condensation or
dehydration reactions that link monomers. Each reaction removes two hydrogen
atoms and one oxygen atom to form water.
Carbohydrate (starch)
Amino
acids
Chemical Reactions
Chemical reactions are the foundation of all life processes. A chemical reaction
occurs when new bonds form or old bonds break between atoms. After a chemical reaction has occurred, the atoms of the reactants are arranged differently to
yield products with new chemical properties.
Each chemical reaction involves energy changes. Chemical energy is a
form of energy that is stored in the bonds that hold molecules together. The
total amount of energy present at the beginning and end of a chemical reaction is the same. Although energy can neither be created nor destroyed, it
may be converted from one form to another. The conversion of one molecule
into another often involves a series of reactions. The series of biochemical
reactions needed to go from a raw material to the final product is called a
metabolic pathway.
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Protein
Fatty acids
Lipid (triglyceride)
Figure F6.2 Nutrient monomers and polymers
Starch is a polymer of glucose, and proteins are
polymers of amino acids. Although not true polymers, triglycerides include three fatty acids.
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FOCUS ON Metabolism
4 FOCUS ON Metabolism
Electron
donor
Electron
acceptor
A
B
e–
Oxidation
Compound A
loses an electron.
Oxidation-Reduction Reactions Some chemical reactions involve
the transfer of electrons from one atom or molecule to another. The loss,
gain, and transfer of electrons are important in biological reactions. A
substance that loses an electron is said to be oxidized and one that gains
an electron is said to be reduced. Reactions that transfer electrons are
called oxidation-reduction reactions and are very important in energy
metabolism (Figure F6.3).
Reduction
Compound B
gains an electron.
Free Radicals and Antioxidants Reactions in the body sometimes
result in the formation of free radicals. A free radical is an atom or molecule with one or more unpaired electrons. Having an unpaired electron
makes the molecule unstable, highly reactive, and destructive to nearby
Oxidized
Reduced
molecules. To become stable, a free radical will steal an electron from a
donor
acceptor
surrounding molecule, forming a new free radical in its place. The newly
Figure F6.3 Oxidation-reduction reactions
formed free radical then steals an electron from one of its neighbors,
In this reaction, molecule A (shown in orange) is oxidized
because it gives up an electron. The electron is accepted
beginning a chain reaction that can damage thousands of molecules.
by molecule B (shown in turquoise), so it is said to be
A common example of a free radical is superoxide, which is formed by
reduced.
the addition of an electron to an oxygen molecule. Superoxide radicals
are continuously formed within the mitochondria as a by-product of the
normal reactions of metabolism. Although we typically think of free radicals as damagoxidized Refers to a compound
that has lost an electron or undering, the immune system uses free radicals to mark foreign invaders and damaged tissue so
gone a chemical reaction with
they can be destroyed. A balance between free-radical production and the availability of
oxygen.
antioxidants is needed to prevent the buildup of free radicals, which can cause damage.
Antioxidant defenses within the body, including antioxidant nutrients consumed in the
reduced Refers to a substance
diet, such as vitamin E and vitamin C, protect us from the damaging effects of free radicals
that has gained an electron.
(Figure F6.4).
A
e–
B
oxidation-reduction reaction
A reaction in which electrons are
transferred from a donor molecule
(the reducing agent) to an
acceptor molecule (the oxidizing
agent).
Free
radicals
Damaged
membrane
free radical An atom or group
of atoms that has at least one
unpaired electron and is therefore
unstable and highly reactive and
can cause cellular damage.
antioxidant A substance that
significantly decreases the
adverse effects of free radicals
and other reactive species on
normal physiological function.
To neutralize reactive
electron-scavenging
molecules, such as free
radicals, vitamin E donates
one of its electrons.
Vitamin E
Vitamin E
Vitamin C
Vitamin C
Vitamin E
e–
e–
Vitamin E
The antioxidant function
of vitamin E can be restored
by another antioxidant
vitamin—vitamin C, which
gives an electron back to
vitamin E.
Undamaged
membrane
Neutralized
free radical
Figure F6.4 Antioxidant nutrients protect us from free radical damage
The unsaturated bonds of fatty acids are particularly susceptible to damage by free radicals. The free radicals
steal electrons from the carbon-carbon double bonds, creating a new free radical and initiating a series of
reactions that damage the membrane. Antioxidants such as the vitamin E, shown here, neutralize the free
radicals by donating an electron. Another oxidation-reduction reaction mediated by vitamin C can then donate
an electron to vitamin E to restore its activity.
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F6.2
Metabolic Pathways
Metabolism refers to all of the chemical reactions and metabolic pathways that occur in the
body. Some of these reactions break down complex organic molecules into simpler ones.
These are collectively known as catabolism. Metabolic reactions that combine simple molecules to form the body’s complex structural and functional components are collectively
known as anabolism. Each of the essential nutrients plays a unique role in metabolism.
Catabolic Pathways
Catabolic reactions split up large molecules into smaller molecules, atoms, or ions. For
instance, when starch is converted into glucose, this is a catabolic reaction as is the breakdown of glucose to form carbon dioxide and water. Overall, catabolic reactions are exergonic; they produce more energy than they consume, releasing the chemical energy stored
in the bonds that hold molecules together. Some of this energy is lost as heat, but some
can be captured and used to synthesize a molecule called adenosine triphosphate (ATP),
which can be used as an energy source by the body (Figure F6.5a). ATP can be thought
of as the energy currency of the cell. The chemical bonds of ATP are very high in energy;
when they break, this energy is released and can be used to power body processes, such as
muscle contraction or nerve conduction—or it can be used for anabolic reactions, which
synthesize new molecules needed to maintain and repair body tissues (Figure F6.5b).
catabolism The processes by
which substances are broken
down into simpler molecules
releasing energy.
anabolism Energy-requiring
processes in which simpler
molecules are combined to form
more complex substances.
FOCUS ON Metabolism
F 6.2 Metabolic Pathways 5
adenosine triphosphate (ATP)
The high-energy molecule used
by the body to perform energyrequiring functions.
Anabolic Pathways
When two or more atoms, ions, or molecules combine to form new and larger molecules,
the processes are called anabolic reactions. Glucose, fatty acids, and amino acids that are
not broken down for energy are used in anabolic pathways to synthesize structural, regulatory, or storage molecules (see Figure F6.5b). Glucose molecules can be used to synthesize
glycogen, a storage form of carbohydrate. If the body has enough glycogen, glucose can
also be used to synthesize fatty acids. Fatty acids can be used to synthesize triglycerides that
are stored as body fat. Amino acids can be used to synthesize the various proteins that the
body needs, such as muscle proteins, enzymes, and blood proteins. Excess amino acids can
be converted into fatty acids and stored as body fat. Anabolic reactions are endergonic; they
consume more energy than they produce. They require ATP as a source of energy.
Figure F6.5
(b)
ATP links catabolic and anabolic reactions
Glucose
Amino acids
Fatty acids
(a)
High-energy bonds
P
P
Catabolic pathways
Anabolic pathways
Nutrients used as fuel
Nutrients used as raw materials
P
3 phosphate groups
Adenosine
ATP
Muscle contraction,
kidney function,
and other body work
Adenosine triphosphate (ATP)
(a) ATP consists of an adenosine molecule attached to three
phosphate groups. The bonds between the phosphate groups are
very high in energy, which is released when the bonds are broken.
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(b) Glucose, amino acids, and fatty acids delivered to body cells can be used
either in catabolic reactions to produce ATP or as raw materials in anabolic
reactions that use ATP to synthesize molecules needed by the body.
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FOCUS ON Metabolism
6 FOCUS ON Metabolism
Energy out
Energy in
Energy out
Energy in
Carbohydrate
Diet
Protein
Fat
When you eat more than you need
Glycogen
Glucose
Body protein
Amino acids
Energy
Fatty acids
Adipose tissue
When you eat less than you need
Figure F6.6 Energy balance
When you eat more than you need at the time, some energy is put into body stores. When you haven’t eaten
in a while, you retrieve energy from these stores.
Energy-Yielding Nutrients and Energy Balance
To stay alive, energy must be available to the body at all times. Excess energy can be
stored for later use. When the amount of energy supplied by the diet is insufficient to
meet needs, energy reserves can be tapped to fuel body processes. All the energy in the
human body originates from the energy–yielding nutrients: carbohydrates, fats, and
proteins. After you have eaten, catabolic pathways break down ingested nutrients to provide ATP and anabolic pathways synthesize molecules needed for tissue growth, maintenance, and repair as well as energy storage. Carbohydrate can be stored as glycogen
and excess calories, whether consumed as carbohydrate, fat, or protein, can be stored
as triglycerides in adipose tissue. Between meals, catabolic pathways break down these
energy stores to provide the ATP needed to sustain life. Over time, if the amount of
energy consumed in the energy-yielding nutrients is equal to the amount needed to fuel
body activity and maintain and repair body tissues, the amount of stored energy and
hence body weight remain the same (Figure F6.6).
The Role of Micronutrients in Metabolism
enzymes Protein molecules that
accelerate the rate of specific
chemical reactions without being
changed themselves.
cofactor An inorganic ion or
organic molecule required for
enzyme activity.
coenzyme A small organic
molecule (not a protein but
sometimes a vitamin) that is
necessary for the proper
functioning of many enzymes.
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The chemical reactions of metabolism are facilitated by enzymes. These protein molecules
catalyze, or speed up, the reactions. To be active, most enzymes require the assistance of
helper molecules called cofactors. Some enzymes or enzyme complexes require more than
one cofactor. Some cofactors are inorganic molecules, while others are organic. Many of
the minerals required in the diet (iron, zinc, copper, selenium, magnesium, manganese,
and molybdenum) serve as inorganic cofactors in metabolism. Organic cofactors are
called coenzymes. Many of the vitamins that are required in the diet serve as precursors
to coenzymes or as coenzymes themselves. There are also coenzymes that are not vitamins
because they can be synthesized in the body in sufficient amounts. Coenzymes act as carriers of electrons or chemical groups that are added, removed, or transferred in the chemical
reactions of metabolism (Figure F6.7). For example, folate coenzymes carry single-carbon
groups and are involved in reactions that add a carbon to a molecule. Niacin coenzymes
shuttle electrons in anabolic and catabolic reactions throughout metabolism. Coenzymes
are continuously recycled as part of metabolism.
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Vitamin
7
FOCUS ON Metabolism
F 6 . 3 Breaking Down Nutrients to Provide Energy
Chemical
Group
1 The vitamin combines with
a chemical group to form the
functional coenzyme (active vitamin).
Incomplete
enzyme
Functional
coenzyme
Active
enzyme
2 The functional coenzyme
combines with the incomplete
enzyme to form the active enzyme.
Molecule
3 The active enzyme binds to one
or more molecules and accelerates
the chemical reaction to form one or
more new molecules.
New
molecule
4 The new molecules are released,
and the enzyme and coenzyme (vitamin)
can be reused or separated.
Figure F6.7
Coenzymes
Coenzymes bind to enzymes to promote their activity. They act as carriers of electrons, atoms, or chemical
groups that participate in the reaction. All the B vitamins are coenzymes, but not all vitamins function as
coenzymes.
F6.3
Breaking Down Nutrients
to Provide Energy
Inside cells, a set of catabolic reactions called cellular respiration converts the energy
stored in the chemical bonds of glucose, fatty acids, and amino acids into ATP. Some of
these reactions take place in the cytosol of the cell and proceed in the absence of oxygen. This is referred to as anaerobic metabolism. Others take place in the mitochondria and require oxygen and constitute aerobic metabolism.
cellular respiration The reactions that break down glucose,
fatty acids, and amino acids in
the presence of oxygen to produce carbon dioxide, water, and
energy in the form of ATP.
Cellular Respiration: Glucose Catabolism
anaerobic metabolism Chemical reactions that occur in the
absence of oxygen and partially
break down glucose to yield
pyruvate, water, and two ATP
molecules.
The complete oxidation of glucose via cellular respiration uses six molecules of oxygen to
convert one molecule of glucose into 6 molecules of carbon dioxide, 6 molecules of water,
and about 38 molecules of ATP:
C6H12O6 1 6 O2 →
6 CO2
1 6 H2O 1 ∼38 ATP
Glucose
oxygen
carbon dioxide
water
Glucose is the only one of the energy-yielding nutrients that can provide ATP in the
absence of oxygen. This affects the way body processes are fueled during intense exercise,
when the demand for ATP exceeds the ability to deliver enough oxygen to support aerobic
metabolism.
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aerobic metabolism Chemical reactions that occur in the
presence of oxygen and can
completely break down glucose to
yield carbon dioxide, water, and
as many as 38 ATP molecules.
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FOCUS ON Metabolism
8 FOCUS ON Metabolism
CO2
O2
Lungs
5 Carbon dioxide is
exhaled through
the lungs.
CO2
O2
1 The respiratory system
takes in oxygen and
delivers it to the blood.
2 The cardiovascular system
circulates the oxygen-rich
blood throughout the body.
Heart
O2
Blood vessels
3 Oxygen is taken up by
CO2
CO2
4 Carbon dioxide is
carried away from the
muscle by the blood.
the muscles and other
tissues and used in
aerobic metabolism,
producing carbon dioxide
as a waste product.
Figure F6.8 Oxygen and carbon dioxide
Cells need oxygen for aerobic metabolism. Oxygen is inhaled through the lungs, and it is delivered to cells
by the blood. Aerobic metabolism produces carbon dioxide as a metabolic waste product. The carbon dioxide
produced by cells is transferred in the blood to the lungs for elimination.
The oxygen needed for cellular respiration is brought into the body by the respiratory
system and delivered to cells by the circulatory system. The carbon dioxide produced as
a by-product of cellular respiration is transported in the blood to the lungs where it is
eliminated in exhaled air (Figure F6.8).
glycolysis (also called anaerobic
metabolism) Metabolic reactions
in the cytosol of the cell that
split glucose into two 3-carbon
pyruvate molecules, yielding two
ATP molecules.
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Glycolysis: Anaerobic Metabolism The first stage of cellular respiration takes
place in the cytosol of the cell and is called glycolysis, meaning “glucose breakdown.”
Because oxygen isn’t needed for this reaction, glycolysis is also called anaerobic metabolism. In glycolysis, the 6-carbon sugar glucose is broken into two 3-carbon pyruvate
molecules (Figure F6.9). These reactions generate two molecules of ATP for each molecule of glucose and release hydrogen ions and high-energy electrons that are passed
to nicotinamide adenine dinucleotide (NAD), a coenzyme form of the vitamin niacin, converting it to NADH. NADH shuttles the electrons and hydrogen ions to the
last stage of cellular respiration: the electron transport chain. When oxygen is limited,
NADH cannot release the electrons, and no further metabolism of glucose or production of ATP occurs.
During intense exercise, the demand for ATP to fuel muscle contraction exceeds the
ability of the lungs and circulatory system to deliver oxygen to the muscles and generate the ATP by aerobic pathways. To allow vigorous activity to continue, extra ATP must
be generated by anaerobic metabolism. Anaerobic metabolism can use only glucose as an
energy source so it rapidly depletes body glucose stores. This limits how long intense activity can be sustained. Lower-intensity exercise relies on aerobic metabolism and can use
fatty acids as well as glucose to fuel activity. This allows aerobic exercise to continue for a
much longer time period than anaerobic exercise (see Chapter 13).
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C
1
Glycolysis
C
O
C
C
C
Cytosol
C
Anaerobic
metabolism
1 Glucose
ATP
e–
NADH
C C C
2 Pyruvate
2
CoA
Acetyl–CoA
formation
Mitochondrion
2CO2
e–
C C CoA
2 Acetyl–CoA
ATP
9
FOCUS ON Metabolism
F 6 . 3 Breaking Down Nutrients to Provide Energy
NADH
3
Citric
acid
cycle
4CO2
Aerobic
metabolism
e–
NADH
FADH2
High-energy
electrons
4
6H2O
ATP
6O2
e–
ADP
e–
Electron
transport
chain
Inner membrane
H+
H+
molecules of
1 In the cytosol of the cell, glycolysis splits glucose, a six-carbon molecule, into two
–
pyruvate, a three-carbon molecule. This step releases high-energy electrons (e ) that are
picked up by NAD to form NADH, and two molecules of ATP per molecule of glucose.
2 When oxygen is available, pyruvate can be used to produce more ATP in the mitochondria. The first
step is to remove one carbon as carbon dioxide from each pyruvate. This produces a two-carbon
molecule that combines with coenzyme A (CoA) to form acetyl-CoA and releases high-energy
electrons that are picked up by NAD, forming NADH.
3 Each acetyl-CoA enters the citric acid cycle, where two carbons are lost as carbon dioxide,
high-energy electrons are released and picked up by NAD or FAD (forming NADH and FADH2,
respectively), and a small amount of ATP is produced.
4 Most ATP is produced in the final step of cellular respiration: the electron transport chain. Here,
the energy from the high-energy electrons released in previous steps pumps hydrogen ions
across the inner mitochondrial membrane. As the hydrogen ions flow back the energy is used to
convert ADP to ATP. The electrons are finally combined with oxygen and hydrogen to form water.
Figure F6.9
Cellular respiration
The reactions of cellular respiration split the bonds between carbon atoms in glucose, releasing energy that
is used to add a phosphate group to ADP, to form ATP. ATP is used to power the energy-requiring processes in
the body.
Acetyl-CoA Formation When oxygen is present, aerobic metabolism can proceed.
Formation of acetyl coenzyme A (acetyl-CoA) is a transition step that prepares pyruvate
for entrance into the citric acid cycle. In the mitochondria, one carbon is removed from
pyruvate and released as CO2. The remaining two-carbon compound combines with a
molecule of coenzyme A (CoA) to form acetyl-CoA (see Figure F6.9). High-energy electrons are released and passed to NAD to form NADH, which transports them to the last
stage of cellular respiration. Acetyl-CoA then enters the third stage of breakdown: the
citric acid cycle. In addition to coenzyme A (which includes the B vitamin pantothenic
acid as part of its structure) and NAD, a coenzyme form of riboflavin called flavin adenine
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FOCUS ON Metabolism
10 F OCUS O N Metabolism
dinucleotide (FAD) and the thiamin coenzyme thiamin pyrophosphate (TPP) are required
for the conversion of pyruvate to acetyl-CoA.
Citric Acid Cycle In the third stage, acetyl-CoA combines with oxaloacetate, a four-carbon
molecule derived from carbohydrate, to form a six-carbon molecule called citric acid and begin
the citric acid cycle (see Figure F6.9). The reactions of the citric acid cycle then remove one carbon at a time to produce carbon dioxide. After two carbons have been removed in this manner, a four-carbon oxaloacetate molecule is re-formed, and the cycle can begin again. These
chemical reactions produce two ATP molecules per glucose molecule and also release highenergy electrons, which are passed to NAD or FAD to form NADH and FADH2, respectively,
for transport to the fourth and last stage of cellular respiration: the electron transport chain.
Electron Transport Chain The electron transport chain consists of a series of molecules, most
of which are proteins, associated with the inner membrane of the mitochondria and involves a
series of oxidation-reduction reactions. The electrons carried by NADH and FADH2 are transferred to this series of electron carriers and passed down the chain. The electrons are finally
combined with oxygen and with the addition of two hydrogen ions form water. As the electrons
are passed along, their energy is released and used to transport hydrogen ions across the inner
mitochondrial membrane, creating an electrical and pH gradient across the membrane. This is
analogous to water held behind a dam; when the water flows through the dam past turbines,
the energy can be used to generate electrical energy. When the hydrogen ions flow through the
membrane past an enzyme called ATP synthase, the energy is used to convert ADP to ATP.
Breaking Down Triglycerides for Energy
beta-oxidation (␤-oxidation) The
first step in the production of ATP
from fatty acids. This pathway
breaks the carbon chain of fatty
acids into two-carbon units that
form acetyl-CoA and releases
high-energy electrons that are
passed to the electron transport
chain.
Triglycerides consumed in the diet or stored in the body provide a source of energy. The
first step is to split the triglycerides into glycerol and fatty acids (Figure F6.10). The majority of ATP produced from triglyceride metabolism is from the oxidation of fatty acids.
In the first step of fatty acid breakdown, called beta-oxidation (␤-oxidation), the
carbon chain of a fatty acid is split into two-carbon units that form acetyl-CoA and
release high-energy electrons that are shuttled to the electron transport chain by FADH2
and NADH (Figure F6.11).
The acetyl-CoA derived from ␤-oxidation combines with oxaloacetate to enter the
citric acid and proceed through aerobic metabolism, as shown in figure F6.11. The highenergy electrons released in both ␤-oxidation and the citric acid cycle are used to generate ATP. When compared to glucose, fatty acid molecules contain less oxygen and more
carbon in their structure and thus require more oxidation to become carbon dioxide and
water. The amount of ATP generated per gram of fatty acids is therefore greater than can
be generated per gram of glucose. This is the reason fat provides more calories than carbohydrate; 9 kcals per gram of fat compared to 4 kcals per gram of glucose.
The glycerol from triglyceride breakdown can also be used to produce ATP. Glycerol
makes up only a small proportion of the carbon in a triglyceride molecule, so the amount
of ATP that results is small.
Triglyceride
3 fatty acids
+
Glycerol
Carbon chain
(variable length)
H
O
H
H C
C
O C H
H
H C
H
C OH
HO C H
H
H
H
O
H C
C
H
O C H
H
+
3
H2O
H C
O
C OH
+
HO C H
H
H
O
H C
C
H
O
H
O C H
H
H C
H
O
C OH
HO C H
H
Figure F6.10 Triglyceride breakdown
The breakdown of a triglyceride is a hydrolysis reaction in which the addition of three molecules of water
splits the triglyceride into three fatty acids and one molecule of glycerol.
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Figure F6.11 Fatty acid metabolism
Fatty acids provide most of the energy
stored in a triglyceride molecule.
C
Glycolysis
C
O
C
C
Cytosol
C
C
Anaerobic
metabolism
Glucose
C
11
ATP
C
4
C
NADH
e–
C C C
Pyruvate
Glycerol
CoA
Acetyl–CoA
formation
Mitochondrion
CO2
e–
NADH
FOCUS ON Metabolism
F 6 . 3 Breaking Down Nutrients to Provide Energy
2
C C CoA
Acetyl–CoA
Citric
acid
cycle
CO2
Aerobic
metabolism
e–
ATP
NADH
FADH2
3
NADH
FADH2
e–
H2O
ATP
O2
e–
ADP
e–
Electron
transport
chain
H+
H+
Inner membrane
1
Fatty acid
8 Acetyl–CoA
H O
C C
H
S
CoA
H
NADH
FADH2
e–
H
H
C
H C
C
C
C
C
C
C
C
C
C
C
C
C
C
O
C
+ 8 CoA
OH
Fatty acid (palmitic acid)
1 Fatty acids are transported into the mitochondria where b-oxidation splits the carbon chains into two-carbon
units that form acetyl-CoA and produces high-energy electrons that are transported by NADH and FADH2.
b-Oxidation of the 16-carbon palmitic acid molecule, shown here, yields 8 molecules of acetyl-CoA.
2 If oxygen and enough carbohydrate are available, acetyl-CoA combines with oxaloacetate to enter the citric
acid cycle, producing two molecules of carbon dioxide and releasing high-energy electrons that are shuttled
by NADH and FADH2 to the electron transport chain.
3 In the final step of aerobic metabolism, the energy in the high-energy electrons released from b-oxidation
and the citric acid cycle is trapped and used to produce ATP and water.
4 Glycerol molecules, from triglyceride breakdown, contain three carbon atoms. They can be used to produce
small amounts of ATP.
Using Amino Acids for Energy
Although carbohydrate and fat are more efficient energy sources, amino acids from
the diet and from body proteins are also used to provide energy. Before this can occur, the
nitrogen-containing amino group must be removed from the amino acids in a process called
deamination (Figure F6.12). Deamination requires the coenzyme pyridoxal phosphate (PLP),
which is the active form of vitamin B6. The amino group that is released is eventually converted
into urea and excreted in the urine. The remaining structure, which is composed of carbon,
hydrogen, and oxygen, can be converted into pyruvate, acetyl-CoA, or intermediates in the citric
acid cycle to produce ATP (see Figure F6.12). As discussed below, the use of amino acids as an
energy source increases both when the diet does not provide enough total energy to meet needs,
as in starvation, and when protein is consumed in excess of need. When both protein and energy
are plentiful, amino acids can be converted into acetyl-CoA and used to synthesize fat for storage.
focus-06.indd 11
deamination The removal of the
amino group from an amino acid.
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FOCUS ON Metabolism
12 F OCUS O N Metabolism
C
Glycolysis
C
O
C
C
C
C
Cytosol
Anaerobic
metabolism
Glucose
ATP
e–
NADH
C C C
Pyruvate
CoA
Acetyl–CoA
formation
2
3
Mitochondrion
CO2
e–
C C CoA
Acetyl–CoA
NADH
Citric
acid
cycle
CO2
e–
4
ATP
NADH
FADH2
High-energy
electrons
e–
5
e–
Electron
transport
chain
H
PLP
O
H2N
1
C
C
OH
Acid
group
Amino
group
Deamination
Aerobic
metabolism
H2O
ATP
O2
ADP
H+
H+
Inner membrane
Side chain
NH2
Amino acid
NH3
Ammonia
1 The amino group is removed by deamination, allowing the carbon
6
compounds that remain to be further metabolized. Deamination
requires the vitamin B6 coenzyme pyridoxal phosphate (PLP).
2 NH3 + CO2
Liver
ATP
H2N
2 Deamination of some amino acids produces three-carbon molecules
that can form pyruvate.
H2O
C
3 Deamination of some amino acids results in molecules that form
NH2
acetyl-CoA, which can enter the citric acid cycle.
Urea
O
Urea
Figure F6.12 Amino acid metabolism
4 Deamination of some amino acids forms intermediates in the citric
acid cycle.
Kidney
Excreted
in urine
In order for the body to use amino acids as an energy source,
the nitrogen-containing amino group must first be removed.
The compounds remaining after the amino group has been
removed are composed of carbon, hydrogen, and oxygen and
can be broken down to produce ATP or used to make glucose
or fatty acids.
focus-06.indd 12
5 High-energy electrons from the breakdown of amino acids are
transferred to the electron transport chain where the energy is trapped
and used to produce ATP and water.
6 The amino group released by deamination produces ammonia, which
is toxic. To protect the body, the liver combines ammonia with carbon
dioxide to form a less toxic waste product called urea, which can be
filtered out of the blood by the kidneys and eliminated from the body in
the urine.
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F6.4
FOCUS ON Metabolism
F 6 . 4 The Metabolism of Feasting and Fasting 13
The Metabolism of Feasting and Fasting
When the body is in the fed state, which is during the few hours after a meal, nutrients are
available to provide energy and synthesize regulatory and structural molecules as well as to
build body stores. When the body is in the fasted state, between meals and during longer
periods without food, adjustments need to be made in metabolism to ensure that energy
is available to body cells. The human body is like a well-run business. When business is
booming, the extra resources are stored for later use and spent on expanding and improving the business. When times are bad, expenditures must be cut and resources must be
taken out of storage and used.
The Fed State
After a meal, the carbohydrate, fat, and protein it provides are digested and the resulting
glucose, fatty acids, and amino acids are absorbed. Some of these nutrients are used to
supply ATP to fuel body processes; some are used to synthesize important structural and
regulatory molecules, and what remains can be converted into storage molecules.
Carbohydrate Stores After a carbohydratecontaining meal, insulin is released, allowing glucose to be taken up by muscle and
adipose tissue cells and stimulating anabolic
pathways (see Chapter 4). Glucose that is not
broken down to meet the body’s immediate
need for energy can be used to synthesize
the glucose storage molecule glycogen. This
process, called glycogenesis, takes place in
both muscle and liver and is activated by
insulin. Muscle glycogen stores provide glucose for the exercising muscle. Liver glycogen supplies glucose to the blood. Glycogen
synthesis requires the input of energy, but
instead of ATP, a similar high-energy compound called uridine triphosphate (UTP) is
used (Figure F6.13).
glycogenesis The conversion of
glucose to glycogen for storage.
Diet
Fat
Protein
Carbohydrate
C
Body
proteins
C
UTP
C
O
C
C
C
C
Amino acids
Glucose
Glycogen
Pyruvate
Fat Stores After a meal, some essential fatty
NH2
acids are used for the synthesis of cell membranes and regulatory molecules, and other
fatty acids are broken down to provide energy.
O
Acetyl–CoA
Fatty acids ingested in excess of needs can be H CH
Citric
C OH
acid
stored as fat in adipose tissue. Excess energy
H
cycle
consumed as fat is packaged in chylomicrons
Fatty acids
ATP
ATP
Electron
and transported directly from the intestines
transport
to the adipose tissue. Because the fatty acids
chain
in our body fat come from the fatty acids we
Fatty acids
eat, what we eat affects the fatty acid composiGlycerol
tion of our adipose tissue; therefore, if you eat
more saturated fat, there will be more saturated fat stored in your adipose tissue.
Once glycogen stores are full, excess
energy consumed as carbohydrate can also
Triglycerides
be converted into fat. Glucose must first go
for storage
to the liver, where it is broken down to form
Figure
F6.13
Storing
energy
acetyl-CoA, which can be used, although
Excess energy consumed as dietary fat is efficiently stored as body fat. Excess energy from
inefficiently, to synthesize fatty acids, glucose or amino acids can also be converted to body fat, but the metabolic conversions are
These fatty acids are then assembled into less efficient.
focus-06.indd 13
11/07/12 10:22 PM
FOCUS ON Metabolism
14 F OCUS O N Metabolism
triglycerides, which are transported to the adipose tissue in VLDLs. Lipoprotein lipase at
the membrane of cells lining the blood vessels breaks down the triglycerides from both
chylomicrons and VLDLs so that the fatty acids can enter the cells, where they are reassembled into triglycerides for storage (see Figure F6.13).
The ability of the body to store fat is theoretically limitless. Fat cells can increase in
weight by about 50 times, and new fat cells can be synthesized when existing cells reach
their maximum size (see Chapter 7). Because each gram of fat provides 9 kcals, compared
with only 4 kcals per gram from carbohydrate or protein, a large amount of energy can
be stored in the body as fat without a great increase in body size. Even a lean man, whose
body fat is only about 10% of his weight, stores over 50,000 kcals of energy as fat.
When Protein Intake Exceeds Need Excess amino acids are not stored in the body. When
the diet is adequate in energy and high in protein, amino acids that are not needed to synthesize body proteins or other nitrogen-containing molecules are deaminated and the carbon
compounds that remain can be oxidized to produce ATP. If both energy and protein intake
exceeds needs, the extra amino acids are converted, although inefficiently, into fatty acids,
stored as triglycerides in adipose tissue, and can contribute to weight gain (see Figure F6.13).
The Fasted State
gluconeogenesis The synthesis
of glucose from simple noncarbohydrate molecules. Amino acids
from protein are the primary
source of carbons for glucose
synthesis.
Between meals and during longer periods without food, regulatory mechanisms shift
metabolism from storing excesses to retrieving energy from body stores. Pathways that produce ATP from the breakdown of energy-yielding nutrients are still in place, but adjustments are made to ensure that blood glucose levels are maintained and to conserve proteins
that are essential to body function.
Providing Glucose Since the brain must obtain some of its energy from glucose, maintaining blood glucose levels within the normal range is a metabolic priority. When glucose
is not being supplied by the diet, it can come from the breakdown of glycogen as well as
hormone-sensitive lipase An
from synthesis via gluconeogenesis. Both of these pathways are stimulated by release of
enzyme present in adipose cells
the hormone glucagon (see Chapter 4). Gluconeogenesis, which occurs in liver and kidney
that responds to chemical signals
cells, is an energy-requiring process that synthesizes glucose from three-carbon molecules.
by breaking down triglycerides
These three-carbon molecules come primarily from amino acids derived from protein
into fatty acids and glycerol for
breakdown (Figure F6.14). When energy is deficient, body proteins, such as enzymes and
release into the bloodstream.
muscle proteins, are broken down into amino acids. Some of these amino
C
acids, referred to as glucogenic amino acids, form pyruvate or intermediates in the citric acid cycle, which can then be used to make glucose.
O
C
A small amount of glucose can also be made from glycerol from triglycerC
C
ide breakdown. Fatty acids and other amino acids, referred to as ketogenic
C
C
amino acids, cannot be used to make glucose because the reactions that
Glucose
break them down produce primarily two-carbon molecules that form
acetyl-CoA. Both ketogenic and glucogenic amino acids can be broken
Gluconeogenesis
ATP
down to provide ATP (see Figure F6.12).
Gluconeogenesis is essential for meeting the body’s immediate need
Pyruvate
Glycerol
for glucose when energy and/or carbohydrate intake is very low, but it uses
amino acids from proteins that could be used for other essential functions
such as growth and maintenance of muscle tissue. Since adequate dietary
NH3
carbohydrate eliminates the need to use amino acids from protein to synthesize glucose, carbohydrate is said to “spare protein.”
C
Citric
acid
cycle
Amino acids
Figure F6.14 Substrates for gluconeogenesis
The primary source of three-carbon molecules for
gluconeogenesis is amino acids that break down to form
pyruvate or intermediates in the citric acid cycle.
A small amount of glucose can be made from glycerol
from triglyceride breakdown.
focus-06.indd 14
Short-Term Fast In the fasting state, body fat stores are broken down
to release fatty acids as a source of energy. In this situation, the enzyme
hormone-sensitive lipase inside the fat cells receives a hormonal signal
that turns on enzyme activity so it begins breaking down stored triglycerides. The fatty acids and glycerol are released directly into the blood, where
they can be taken up by cells throughout the body to produce ATP. Most
tissues in the body can use fatty acids as an energy source, but since fatty
acids are unable to cross the blood-brain barrier, they are inaccessible to
11/07/12 10:22 PM
Muscle
Protein
Amino acids
Liver
Glycogen
Amino
acids
Glucose
Blood glucose
Blood vessel
Glycerol
Fatty acids
Brain
FOCUS ON Metabolism
F 6 . 4 The Metabolism of Feasting and Fasting 15
Ketones
Triglycerides
Glycerol
Fatty
acids
Adipose tissue
Most body tissues
Figure F6.15
The metabolism of starvation
During starvation, gluconeogenesis provides glucose by synthesizing it from three-carbon molecules, derived
primarily from amino acids. Compounds that contain two carbons, such as acetyl-CoA derived from fatty acid
breakdown, cannot be used to make glucose, and the liver converts them to ketones.
the brain. During the first two or three days of starvation, fatty acids are the main fuel for
most body tissues. The brain continues to use glucose because the use of fatty acids by other
tissues has made more glucose available to the brain.
Long-Term Fast The brain requires about 120 g of glucose per day (about 30 teaspoons).
If it continues to use glucose at this rate during fasting, large amounts of body protein will
need to be broken down to supply it. To spare protein, after about three days of fasting, the
brain begins to obtain about half of its energy from molecules known as ketones or ketone
bodies. Ketones are smaller molecules than fatty acids, so they can cross into the brain and
be used for energy.
Ketones are formed in moderate amounts during sleep and at other times when no
carbohydrates are available. This occurs because the liver conserves citric acid cycle intermediates such as oxaloacetate that can be used to synthesize glucose by gluconeogenesis.
When the amount of acetyl-CoA generated exceeds the availability of oxaloacetate, acetylCoA cannot enter the citric acid cycle, so it is used to make ketones. Ketone production is
a normal response to starvation or to a diet very low in carbohydrate. Even during a shortterm fast, the increase in fatty acid breakdown and the limited supply of glucose causes the
amount of acetyl-CoA formed to exceed the amount of oxaloacetate present, resulting in
an increase in ketone formation. Ketones circulate in the blood and can be used by muscle,
heart, and other tissues as an energy source. After about three days of fasting, even the
brain adapts and can obtain about half of its energy from ketones. The use of ketones for
energy helps spare glucose and decreases the amount of protein that must be broken down
to synthesize glucose. The metabolic adaptations that occur during starvation are summarized in Figure F6.15.
The production of ketone bodies reduces the amount of glucose required by the brain,
but the amount needed still exceeds what can be produced by liver gluconeogenesis from
glycerol. The remaining glucose must be supplied by amino acids from breakdown of the
body’s own proteins (see Figure F6.15).
focus-06.indd 15
ketones or ketone bodies
Molecules formed in the liver
when there is not sufficient
carbohydrate to completely
metabolize the two-carbon units
produced from fat breakdown.
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