The Building Reactions—Anabolism
CHAPTER 7
Metabolism: Transportation
and Interaction
 All the energy that sustains human life
initially comes from the sun—the ultimate
source of energy.
 During photosynthesis, plants make simple
sugars from carbon dioxide and capture the
sun’s light energy in the chemical bonds of
those sugars. Then human beings eat either
the plants or animals that have eaten the
plants. These foods provide energy.
 During metabolism, the body releases
energy, water, and carbon dioxide (and
other waste products).
 Photosynthesis: the process by which green
plants use the sun’s energy to make
carbohydrates from carbon dioxide and
water.
 Fuel: compounds that cells can use for
energy.
 The major fuels include glucose, fatty acids,
and amino acids; other fuels include ketone
bodies, lactate, glycerol, and alcohol.
 Metabolism: the sum total of all the chemical
reactions that go on in living cells. Energy
metabolism includes all the reactions by which
the body obtains and expends the energy from
food. • metaballein = change
Chemical Reactions in the Body
The Site of Metabolic Reactions—Cells
 The human body is made up of trillions of cells,
and each cell busily conducts its metabolic work
all the time.
 The type and extent of metabolic activities vary
depending on the type of cell, but of all the
body’s cells, the liver cells are the most
versatile and metabolically active.
 Glucose molecules may be joined together to
make glycogen chains.
 Glycerol and fatty acids may be assembled into
triglycerides.
 Amino acids may be linked together to make
proteins.
 Each of these reactions starts with small, simple
compounds and uses them as building blocks to
form larger, more complex structures.
 Anabolism is the building up of body
compounds.
The Breakdown Reactions—Catabolism
 Catabolism is the breaking down of body
compounds.
 Catabolic reactions release energy.
The Transfer of Energy in Reactions—ATP
 Some of the energy released during the
breakdown of glucose, glycerol, fatty acids, and
amino acids from foods is captured in the high-
energy storage compound ATP (adenosine
triphosphate).
 ATP, as its name indicates, contains three
phosphate groups
 The negative charges on the phosphate groups
make ATP vulnerable to hydrolysis.
 When the bonds between the phosphate
groups are hydrolyzed, they readily break,
splitting off one or two phosphate groups and
releasing energy.
 In this way, ATP provides the energy that
powers all the activities of living cells.
 The hydrolysis of ATP occurs simultaneously
with reactions that will use that energy—a
metabolic duet known as coupled reactions.
 The body uses ATP to transfer the energy
released during catabolic reactions to power
its anabolic reactions.
 The body converts the chemical energy of food
to the chemical energy of ATP with about 50
percent efficiency, radiating the rest as heat.
 Some energy is lost as heat again when the
body uses the chemical energy of ATP to do its
work—moving muscles, synthesizing
compounds, or transporting nutrients.
  ATP or adenosine triphosphate: a common
high-energy compound composed of a purine
(adenine), a sugar (ribose), and three phosphate
groups.
 Coupled reactions: pairs of chemical reactions
in which some of the energy released from the
breakdown of one compound is used to create a
bond in the formation of another compound.
The Helpers in Metabolic Reactions—Enzymes and
Coenzymes
 Metabolic reactions almost always require
enzymes to facilitate their action.
 Enzyme helpers are called coenzymes.
 Coenzymes are complex organic molecules that
associate closely with most enzymes but are not
proteins themselves.
 Without its coenzyme, an enzyme cannot
function.
 Some of the B vitamins serve as coenzymes
that participate in the energy metabolism of
glucose, glycerol, fatty acids, and amino acids.
 Coenzymes: complex organic molecules that
work with enzymes to facilitate the enzymes’
activity. Many coenzymes have B vitamins as
part of their structures.
IN SUMMARY
During digestion the energy-yielding nutrients—
carbohydrates, lipids, and proteins—are broken down
to glucose (and other monosaccharides), glycerol, fatty
acids, and amino acids. With the help of enzymes and
coenzymes, the cells use these products of digestion to
build more complex compounds (anabolism) or break
them down further to release energy (catabolism).
High-energy compounds such as ATP may capture the
energy released during catabolism.
Breaking Down Nutrients for Energy
 During digestion, the body breaks down the
three energy yielding nutrients—carbohydrates,
lipids, and proteins—into four basic units that
can be absorbed into the blood:
• From carbohydrates—glucose (and other
monosaccharides)
• From fats (triglycerides)—glycerol and fatty
acids
• From proteins—amino acids
 The body uses carbohydrates and fats for most
of its energy needs.
 Amino acids are used primarily as building
blocks for proteins, but they also enter energy
pathways, contributing about 10 to 15 percent
of the day’s energy use.
 Glucose, glycerol, fatty acids, and amino acids
are the basic units derived from food, but a
molecule of each of these compounds is made
of still smaller units, the atoms—carbons,
nitrogens, oxygens, and hydrogens. During
catabolism, the body separates these atoms
from one another.
 Glucose has 6 carbons
 Glycerol has 3 carbons
 A fatty acid usually has an even number of
carbons, commonly 16 or 18 carbons
 An amino acid has 2, 3, or more carbons with a
nitrogen attached
 Pyruvate: a 3-carbon compound that plays a
key role in energy metabolism. Can be used to
make glucose.
 Acetyl CoA: a 2-carbon compound (acetate, or
acetic acid) to which a molecule of CoA is
attached. Cannot be used to make glucose.
 The parts of protein and fat that can be
converted to pyruvate can provide glucose for
the body, whereas the parts that are converted
to acetyl CoA cannot provide glucose but can
readily provide fat.
 The body must have glucose to fuel the
activities of the central nervous system and red
blood cells.
 Without glucose from food, the body will
devour its own lean (protein containing) tissue
to get the amino acids needed to make glucose.
 Giving the body only fat, which delivers mostly
acetyl CoA, puts it in the position of having to
break down protein tissue to make glucose.
 Giving the body only protein puts it in the
position of having to convert protein to glucose.
 The best diet provides ample carbohydrate,
adequate protein, and some fat.
 Eventually, all of the energy-yielding nutrients
can enter the final energy pathways of the TCA
cycle and the electron transport chain.
(Similarly, people from three different cities can
all enter an interstate highway and travel to the
same destination.)
  The TCA cycle is also called the citric acid cycle
or the Kreb’s cycle. The electron transport
chain is also called the respiratory chain.
 CoA : coenzyme A; the coenzyme derived from
the B vitamin pantothenic acid and central to
energy metabolism.
 TCA cycle or tricarboxylic acid cycle: a series of
metabolic reactions that break down molecules
of acetyl CoA to carbon dioxide and hydrogen
atoms; also called the citric acid cycle or the
Kreb’s cycle after the biochemist who
elucidated its reactions.
 Electron transport chain: the final pathway in
energy metabolism that transports electrons
from hydrogen to oxygen and captures the
energy released in the bonds of ATP.
Glucose
Pyruvate-to-Lactate (Anaerobic)
 Liver cells can convert the monosaccharides
fructose and galactose to compounds that enter
the same energy pathways.
Glucose-to-Pyruvate
 The first pathway glucose takes on its way to
yield energy is called glycolysis (glucose
splitting).
 In a series of reactions, the 6-carbon glucose is
converted to similar 6-carbon compounds
before being split in half, forming two 3-carbon
compounds.
 These 3-carbon compounds continue along the
pathway until they are converted to pyruvate.
 Thus the net yield of one glucose molecule is
two pyruvate molecules.
 The net yield of energy at this point is small; to
start glycolysis, the cell uses a little energy and
then produces only a little more than it had to
invest initially.
 As glucose breaks down to pyruvate, hydrogen
atoms with their electrons are released and
carried to the electron transport chain by
coenzymes made from the B vitamin niacin.
 Glycolysis: the metabolic breakdown of glucose
to pyruvate. Glycolysis does not require oxygen
(anaerobic).
Pyruvate’s Options—Anaerobic or Aerobic
 Whenever carbohydrates, fats, or proteins are
broken down to provide energy, oxygen is
always ultimately involved in the process.
 When the body needs energy quickly, pyruvate
is converted to lactate.
 The breakdown of glucose-to-pyruvate-to-
lactate proceeds without oxygen—it is
anaerobic.
 This anaerobic pathway yields energy quickly,
but it cannot be sustained for long—a couple of
minutes at most.
 When energy expenditure proceeds at a slower
pace, pyruvate breaks down to acetyl CoA in
an aerobic pathway.
 Aerobic pathways produce energy more
slowly, but because they can be sustained for a
long time, their total energy yield is greater
 Coenzymes carry the hydrogens from glucose
breakdown to the electron transport chain.
 If the electron transport chain is unable to
accept these hydrogens, as may occur when
cells lack sufficient mitochondria or in the
absence of sufficient oxygen, pyruvate can
accept the hydrogens.
 By accepting the hydrogens, pyruvate becomes
lactate, and the coenzymes are freed to return
to glycolysis to pick up more hydrogens.
 In this way, glucose can continue providing
energy anaerobically for a while.
 The production of lactate occurs to a limited
extent even at rest.
 During high intensity exercise, however, the
muscles rely heavily on anaerobic glycolysis to
produce ATP quickly, and the concentration of
lactate increases dramatically
 The rapid rate of glycolysis produces abundant
pyruvate and releases hydrogen-carrying
coenzymes more rapidly than the mitochondria
can handle them.
 To enable exercise to continue at this intensity,
pyruvate is converted to lactate and coenzymes
are released, which allows glycolysis to
continue.
 Making lactate from pyruvate consumes two
hydrogen ions, which actually diminishes
acidity and improves the performance of tired
muscles.
  One possible fate of lactate is to be transported
from the muscles to the liver. There the liver
can convert the lactate produced in muscles to
glucose, which can then be returned to the
muscles. This recycling process is called the Cori
cycle
 Muscle cells cannot recycle lactate to glucose
because they lack a necessary enzyme.
Pyruvate-to-Acetyl CoA (Aerobic)
 If the cell needs energy and oxygen is available,
pyruvate molecules enter the mitochondria of
the cell.
 There a carbon group (COOH) from the 3-
carbon pyruvate is removed to produce a 2-
carbon compound that bonds with a molecule
of CoA, becoming acetyl CoA.
 The carbon group from pyruvate becomes
carbon dioxide, which is released into the
blood, circulated to the lungs, and breathed
out.
 The step from pyruvate to acetyl CoA is
metabolically irreversible: a cell cannot retrieve
the shed carbons from carbon dioxide to
remake pyruvate and then glucose.
Acetyl CoA’s Options
 Acetyl CoA has two main functions—it may be
used to synthesize fats or to generate ATP.
 When ATP is abundant, acetyl CoA makes fat,
the most efficient way to store energy for later
use when energy may be needed.
 Any molecule that can make acetyl CoA—
including glucose, glycerol, fatty acids, and
amino acids—can make fat.
 CoA can be used as a building block for fatty
acids, but it cannot be used to make glucose or
amino acids.
 When ATP is low and the cell needs energy,
acetyl CoA may proceed through the TCA cycle,
releasing hydrogens, with their electrons, to the
electron transport chain.
 When acetyl CoA from the breakdown of
glucose enters the aerobic pathways of the TCA
cycle and electron transport chain, much more
ATP is produced than during glycolysis.
 The role of glycolysis is to provide energy for
short bursts of activity and to prepare glucose
for the later energy pathways.
 Cori cycle: the path from muscle glycogen to
glucose to pyruvate to lactate (which travels to
the liver) to glucose (which can travel back to
the muscle) to glycogen.
 Mitochondria: the cellular organelles
responsible for producing ATP aerobically;
made of membranes (lipid and protein) with
enzymes mounted on them.
 Lactate: a 3-carbon compound produced from
pyruvate during anaerobic metabolism.
IN SUMMARY
 The breakdown of glucose to energy begins
with glycolysis, a pathway that produces
pyruvate.
 Glucose can be synthesized only from pyruvate
or compounds earlier in the pathway.
 Pyruvate may be converted to lactate
anaerobically or to acetyl CoA aerobically.
 Once the commitment to acetyl CoA is made,
glucose is not retrievable; acetyl CoA cannot go
back to glucose.
Glycerol and Fatty Acids
Glycerol-to-Pyruvate
 Glycerol is a 3-carbon compound like pyruvate
but with a different arrangement of H and OH
on the C.
 Glycerol can easily be converted to another 3-
carbon compound that can go either “up” the
pathway to form glucose or “down” to form
pyruvate and then acetyl CoA.
Fatty Acids-to-Acetyl CoA
 Fatty acids are taken apart 2 carbons at a time
in a series of reactions known as fatty acid
oxidation.
 Each 2-carbon fragment splits off and combines
with a molecule of CoA to make acetyl CoA.
 As each 2-carbon fragment breaks off from a
fatty acid during oxidation, hydrogens and their
electrons are released and carried to the
electron transport chain by coenzymes made
from the B vitamins riboflavin and niacin.
Fatty Acids Cannot Be Used to Synthesize Glucose
  Red blood cells and the brain and nervous
system depend primarily on glucose as fuel.
 When carbohydrate is unavailable, the liver
cells can make glucose from pyruvate and other
3-carbon compounds, such as glycerol.
 Cells cannot make glucose from the 2-carbon
fragments of fatty acids.
 Almost all dietary fats are triglycerides and that
triglycerides contain only one small molecule of
glycerol with three fatty acids.
 The glycerol can yield glucose, but that
represents only 3 of the 50 or so carbon atoms
in a triglyceride—about 5 percent of its weight.
The other 95 percent cannot be converted to
glucose.
 Making glucose from noncarbohydrate sources
is called gluconeogenesis. The glycerol portion
of a triglyceride and most amino acids can be
used to make glucose. The liver is the major site
of gluconeogenesis, but the kidneys become
increasingly involved under certain
circumstances, such as starvation.
 Fatty acid oxidation: the metabolic breakdown
of fatty acids to acetyl CoA; also called beta
oxidation.
IN SUMMARY
 The body can convert the small glycerol portion
of a triglyceride to either pyruvate (and then
glucose) or acetyl CoA.
 The fatty acids of a triglyceride, on the other
hand, cannot make glucose, but they can
provide abundant acetyl CoA.
 Acetyl CoA may then enter the TCA cycle to
release energy or combine with other molecules
of acetyl CoA to make body fat.
Amino Acids
 Before entering the metabolic pathways, amino
acids are deaminated.
 A 16-carbon fatty acid yields 8 acetyl CoA.
Amino Acids-to-Energy
 Some amino acids can be converted to
pyruvate, others are converted to acetyl CoA,
and still others enter the TCA cycle directly as
compounds other than acetyl CoA.
Amino Acids-to-Glucose
 Amino acids that are used to make pyruvate can
provide glucose, whereas those used to make
acetyl CoA can provide additional energy or
make body fat but cannot make glucose.
 Amino acids entering the TCA cycle directly can
continue in the cycle and generate energy;
alternatively, they can generate glucose.
 Thus protein, unlike fat, is a fairly good source
of glucose when carbohydrate is not available.
 Amino acids that can make glucose via either
pyruvate or TCA cycle intermediates are
glucogenic; amino acids that are degraded to
acetyl CoA are ketogenic.
IN SUMMARY
 The body can use some amino acids to produce
glucose, whereas others can be used either to
provide energy or to make fat.
 Before an amino acid enters any of these
metabolic pathways, its nitrogen-containing
amino group must be removed through
deamination.
Breaking Down Nutrients for Energy—In
Summary
 To obtain energy, the body uses glucose and
fatty acids as its primary fuels and amino acids
to a lesser extent.
 To make glucose, the body can use all
carbohydrates and most amino acids, but it can
convert only 5 percent of fat (the glycerol
portion) to glucose.
 Fatty acids cannot make glucose.
 To make proteins, the body needs amino acids.
 It can use glucose and glycerol to make some
nonessential amino acids when nitrogen is
available; it cannot use fatty acids to make body
proteins.
 Finally, when energy intake exceeds the body’s
needs, all three energy-yielding nutrients can
contribute to body fat stores.
The Final Steps of Catabolism
  The TCA cycle reactions take place in the inner
compartment of the mitochondria.
The TCA Cycle
 Acetyl CoA goes one way only—down to two
carbon dioxide molecules and a coenzyme
(CoA).
 The TCA cycle is a circular path because a 4-
carbon compound known as oxaloacetate is
needed in the first step and it is synthesized in
the last step.
 When oxaloacetate is insufficient, the TCA cycle
slows down, and the cells face an energy crisis.
 Oxaloacetate is made primarily from pyruvate,
although it can also be made from certain
amino acids.
 Oxaloacetate must be available for acetyl CoA
to enter the TCA cycle underscores the
importance of carbohydrates in the diet.
 A diet that provides ample carbohydrate
ensures an adequate supply of oxaloacetate
(because glucose produces pyruvate during
glycolysis).
 Oxaloacetate is the first 4-carbon compound to
enter the TCA cycle.
 Oxaloacetate picks up acetyl CoA (a 2-carbon
compound), drops off one carbon (as carbon
The kCalories-per-Gram Secret Revealed
dioxide), then another carbon (as carbon
dioxide), and returns to pick up another acetyl
CoA.
 As for the acetyl CoA, its carbons go only one
way—to carbon dioxide.
 As acetyl CoA molecules break down to carbon
dioxide, hydrogen atoms with their electrons
are removed from the compounds in the cycle.
 Each turn of the TCA cycle releases a total of
eight electrons. Coenzymes made from the B
vitamins niacin and riboflavin receive the
hydrogens and their electrons from the TCA
cycle and transfer them to the electron
transport chain.
 Oxaloacetate: a carbohydrate intermediate of
the TCA cycle.
The Electron Transport Chain
 In the final pathway, the electron transport
chain, energy is captured in the high-energy
bonds of ATP.
 The electron transport chain consists of a series
of proteins that serve as electron “carriers.
 These carriers are mounted in sequence on the
inner membrane of the mitochondria.
 As the coenzymes deliver their electrons from
the TCA cycle, glycolysis, and fatty acid
oxidation to the electron transport chain, each
carrier receives the electrons and passes them
on to the next carrier.
 These electron carriers continue passing the
electrons down until they reach oxygen at the
end of the chain.
 Oxygen (O) accepts the electrons and combines
with hydrogen atoms (H) to form water (H2O).
That oxygen must be available for energy
metabolism explains why it is essential to life.
 As electrons are passed from carrier to carrier,
hydrogen ions are pumped across the
membrane to the outer compartment of the
mitochondria.
 The rush of hydrogen ions back into the inner
compartment powers the synthesis of ATP. In
this way, energy is captured in the bonds of
ATP.
 The ATP leaves the mitochondria and enters the
cytoplasm, where it can be used for energy.
 All the bonds in the fatty acid are between
carbons and hydrogens.
 Oxygen can be added to all of them—forming
carbon dioxide with the carbons and water with
the hydrogens.
 As this happens, hydrogens are released to
coenzymes heading for the electron transport
chain.
 In glucose, on the other hand, an oxygen is
already bonded to each carbon.
 Thus there is less potential for oxidation, and
fewer hydrogens are released when the
remaining bonds are broken.
 Because fat contains many carbon-hydrogen
bonds that can be readily oxidized, it sends
numerous coenzymes with their hydrogens and
electrons to the electron transport chain where
that energy can be captured in the bonds of
ATP. This explains why fat yields more
kcalories per gram than carbohydrate or
protein.
  ATP holds energy and that kcalories measure
energy; thus the more ATP generated, the more
kcalories have been collected.
 One glucose molecule will yield 30 to 32 ATP
when completely oxidized.
 One 16-carbon fatty acid molecule will yield 129
ATP when completely oxidized.
 Fat is a more efficient fuel source.
 Gram for gram, fat can provide much more
energy than either of the other two energy-
yielding nutrients, making it the body’s
preferred form of energy storage.
IN SUMMARY
 The digestion of carbohydrate yields glucose
(and other monosaccharides); some is stored as
glycogen, and some is broken down to pyruvate
and acetyl CoA to provide energy.
 The acetyl CoA can then enter the TCA cycle and
coenzymes with their electrons are sent to the
electron transport chain to provide more
energy.
 The digestion of fat yields glycerol and fatty
acids; some are reassembled and stored as fat,
and others are broken down to acetyl CoA,
which can enter the TCA cycle and send
coenzymes with electrons to the electron
transport chain to provide energy.
 The digestion of protein yields amino acids,
most of which are used to build body protein or
other nitrogen containing compounds, but
some amino acids may be broken down through
the same pathways as glucose to provide
energy.
 Other amino acids enter directly into the TCA
cycle, and these, too, can be broken down to
yield energy.
Energy Balance
Feasting—Excess Energy
 When a person eats too much, metabolism
favors fat formation.
 Fat cells enlarge regardless of whether the
excess in kcalories derives from protein,
carbohydrate, or fat.
 The pathway from dietary fat to body fat,
however, is the most direct (requiring only a
few metabolic steps) and the most efficient
(costing only a few kcalories).
 To convert a dietary triglyceride to a
triglyceride in adipose tissue, the body
removes two of the fatty acids from the glycerol
backbone, absorbs the parts, and puts them
(and others) together again.
 By comparison, to convert a molecule of
sucrose, the body has to split glucose from
fructose, absorb them, dismantle them to
pyruvate and acetyl CoA, assemble many acetyl
CoA molecules into fatty acid chains, and finally
attach fatty acids to a glycerol backbone to
make a triglyceride for storage in adipose tissue.
 The body uses much less energy to convert
dietary fat to body fat than it does .
 On average, storing excess energy from dietary
fat as body fat uses only 5 percent of the
ingested energy intake, but storing excess
energy from dietary carbohydrate as body fat
requires 25 percent of the ingested energy
intake.
 The pathways from excess protein and excess
carbohydrate to body fat are not only indirect
and inefficient, but they are also less preferred
by the body (having other priorities for using
these nutrients).
 Before entering fat storage, protein must first
tend to its many roles in the body’s lean
tissues, and carbohydrate must fill the
glycogen stores.
Excess Protein
 Lean tissue such as muscle develops in response
to a stimulus such as hormones or physical
activity.
 When a person overeats protein, the body uses
the surplus first by replacing normal daily losses
and then by increasing protein oxidation.
 The body achieves protein balance this way, but
any increase in protein oxidation displaces fat
in the fuel mix.
 Any additional protein is then deaminated, and
the remaining carbons are used to make fatty
 acids, which are stored as triglycerides in
adipose tissue.
 A person can grow fat by eating too much
protein
Excess Carbohydrate
 Compared with protein, the proportion of
carbohydrate in the fuel mix changes more
dramatically when a person overeats.
 The body handles abundant carbohydrate by
first storing it as glycogen, but glycogen storage
areas are limited and fill quickly.
 Because maintaining glucose balance is critical,
the body uses glucose frugally when the diet
provides only small amounts and freely when
supplies are abundant.
 Glucose oxidation rapidly adjusts to the dietary
intake of carbohydrate.
 Excess glucose can also be converted to fat
directly.
 When excess dietary carbohydrate can displace
fat in the fuel mix, carbohydrate spares both
dietary fat and body fat from oxidation— an
effect that may be more pronounced in
overweight people than in lean people.
 The net result: excess carbohydrate contributes
to obesity or at least to the maintenance of an
overweight body.
Excess Fat
 Unlike excess protein and carbohydrate, which
both enhance their own oxidation, eating too
much fat does not promote fat oxidation.
 Instead, excess dietary fat moves efficiently into
the body’s fat stores; almost all of the excess is
stored.
IN SUMMARY
 If energy intake exceeds the body’s energy
needs, the result will be weight gain—
regardless of whether the excess intake is from
protein, carbohydrate, or fat.
 The difference is that the body is much more
efficient at storing energy when the excess
derives from dietary fat.
The Transition from Feasting to
Fasting
 After a meal, glucose, glycerol, and fatty acids
from foods are used as needed and then stored.
 Later, as the body shifts from a fed state to a
fasting one, it begins drawing on these stores.
 Glycogen and fat are released from storage to
provide more glucose, glycerol, and fatty acids
for energy.
 The cells’ work that maintains all life processes
without any conscious effort—represents about
two-thirds of the total energy a person expends
in a day.
 The small remainder is the work that a person’s
muscles perform voluntarily during waking
hours.
 The body’s top priority is to meet the cells’
needs for energy, and it normally does this by
periodic refueling—that is, by eating several
times a day.
 When food is not available, the body turns to its
own tissues for other fuel sources.
 The body is forced to draw on its reserves of
carbohydrate and fat and, within a day or so, on
its vital protein tissues as well when fasting.
Fasting—Inadequate Energy
 During fasting, carbohydrate, fat, and protein
are all eventually used for energy—fuel must be
delivered to every cell
 As the fast begins, glucose from the liver’s
stored glycogen and fatty acids from the
adipose tissue’s stored fat are both flowing into
cells, then breaking down to yield acetyl CoA,
and finally delivering energy to power the cells’
work.
 Several hours later, however, most of the
glucose is used up—liver glycogen is exhausted
and blood glucose begins to fall.
 Low blood glucose serves as a signal that
promotes further fat breakdown and release of
amino acids from muscles.
Glucose Needed for the Brain
  Red blood cells and the cells of the nervous
system need glucose.
 Glucose is their primary energy fuel, and even
when other energy fuels are available, glucose
must be present to permit the energy-
metabolizing machinery of the nervous system
to work.
 Normally, the brain and nerve cells—which
weigh only about three pounds— consume
about half of the total glucose used each day
(about 500 kcalories’ worth).
 About one-fourth of the energy the adult body
uses when it is at rest is spent by the brain.
Protein Meets Glucose Needs
 The need for glucose poses a problem for the
fasting body.
 The body can use its stores of fat, which may be
quite generous, to furnish most of its cells with
energy, but the red blood cells are completely
dependent on glucose, and the brain and nerves
prefer energy in the form of glucose.
 Amino acids that yield pyruvate can be used to
make glucose.
 To obtain the amino acids, body proteins must
be broken down.
 For this reason, body protein tissues such as
muscle and liver always break down to some
extent during fasting.
 The amino acids that can’t be used to make
glucose are used as an energy source for other
body cells.
 The breakdown of body protein is an expensive
way to obtain glucose.
 In the first few days of a fast, body protein
provides about 90 percent of the needed
glucose; glycerol, about 10 percent.
 If body protein losses were to continue at this
rate, death would follow within three weeks,
regardless of the quantity of fat a person had
stored.
 Fortunately, fat breakdown also increases with
fasting—in fact, fat breakdown almost doubles,
providing energy for other body cells and
glycerol for glucose production.
The Shift to Ketosis
 As the fast continues, the body finds a way to
use its fat to fuel the brain.
 It adapts by combining acetyl CoA fragments
derived from fatty acids to produce an alternate
energy source, ketone bodies.
 Normally produced and used only in small
quantities, ketone bodies can efficiently provide
fuel for brain cells.
 Ketone body production rises until, after about
ten days of fasting, it is meeting much of the
nervous system’s energy needs.
 When ketone bodies contain an acid group
(COOH), they are called keto acids.
 Small amounts of keto acids are a normal part
of the blood chemistry, but when their
concentration rises, the pH of the blood drops.
 This is ketosis, a sign that the body’s chemistry
is going awry.
 Acidic blood denatures proteins, leaving them
unable to function.
 Elevated blood ketones (ketonemia) are
excreted in the urine (ketonuria).
 A fruity odor on the breath (known as acetone
breath) develops, reflecting the presence of the
ketone acetone.
Suppression of Appetite
 Ketosis also induces a loss of appetite.
 As starvation continues, this loss of appetite
becomes an advantage to a person without
access to food because the search for food
would be a waste of energy.
 When the person finds food and eats again, the
body shifts out of ketosis, the hunger center
gets the message that food is again available,
and the appetite returns.
Slowing of Metabolism
 In an effort to conserve body tissues for as long
as possible, the hormones of fasting slow
metabolism.
 As the body shifts to the use of ketone bodies, it
simultaneously reduces its energy output and
conserves both its fat and its lean tissue.
 Still the lean (protein-containing) tissues shrink
and perform less metabolic work, reducing
energy expenditures.
  As the muscles waste, they can do less work and
so demand less energy, reducing expenditures
further.
 Although fasting may promote dramatic weight
loss, a low-kcalorie diet and physical activity
better support fat loss while retaining lean
tissue.
Symptoms of Starvation
 The adaptations just described—slowing of
energy output and reduction in fat loss.
 Such adaptations help to prolong their lives and
explain the physical symptoms of starvation:
wasting; slowed heart rate, respiration, and
metabolism; lowered body temperature;
impaired vision; organ failure; and reduced
resistance to disease.
 Psychological effects of food deprivation include
depression, anxiety, and food-related dreams
 The body’s adaptations to fasting are sufficient
to maintain life for a long time— up to two
months.
 Mental alertness need not be diminished, and
even some physical energy may remain
unimpaired for a surprisingly long time.
 Once the body depletes its glycogen reserves, it
begins making glucose from the amino acids of
protein (gluconeogenesis).
 A low-carbohydrate diet may provide abundant
protein from food, but the body still uses some
protein from body tissues.
 Whenever glycogen or protein is broken down,
water is released and urine production
increases.
 Low-carbohydrate diets also induce ketosis, and
ketones can be detected in the urine.
 Ketones form whenever glucose is lacking and
fat breakdown is incomplete.
 Much of this weight loss in ketosis reflects the
loss of glycogen and protein together with
large quantities of body fluids and important
minerals.

IN SUMMARY
 When fasting, the body makes a number of
adaptations: increasing the breakdown of fat to
provide energy for most of the cells, using
glycerol and amino acids to make glucose for
the red blood cells and central nervous system,
producing ketones to fuel the brain, suppressing
the appetite, and slowing metabolism. All of
these measures conserve energy and minimize
losses.

Low-Carbohydrate Diets
 When a person consumes a low-carbohydrate
diet, a metabolism similar to that of fasting
prevails.
 With little dietary carbohydrate coming in, the
body uses its glycogen stores to provide
glucose for the cells of the brain, nerves, and
blood.