Your Body's Metabolism Explained

8
Your
Meta
Bodys
bolism
1. Metabolism
takes place within cells. T/F
2. The body prefers to use carbohydrates for fuel because

very little energy is needed to break them down during metabolism. T/F
3. Fructose is preferable to glucose as an energy

4.
source.
T/F
Lactate buildup during exercise causes a burning
sensation in the legs. T/F
5. Excess dietary
protein is stored in the
muscle and therefore increases muscle size. T/F
6. Fat is the main fuel used during high-intensity

energy metabolism. T/F
7. Alcohol is converted to blood sugar

during metabolism. T/F
8.
B vitamins provide energy. T/F
9. Kilocalories consumed after 7:00 p.m. are automatically
stored as fat and contribute to weight gain.

10. Children with inborn
T/F
errors of metabolism
will outgrow such disorders when they reach puberty. T/F

See page 36 for answers.
wenty-one-year-old Andrew is a
college senior with a biology major
and a full load of coursework during his final semester of school. His
schedule is hectic, with a three-hour
lecture class on Monday and Wednesday
mornings, and eight hours of classes and
labs on Tuesdays and Thursdays. On
these four days of the week, Andrew is
able to grab coffee and a bagel in the
morning, but usually skips lunch, snacking instead on tortilla chips and salsa, or
potato chips, during the afternoon. He
typically doesnt eat a full meal until he gets home around 5 p.m.
By that time, hes tired, irritable, and starving.
Friday is a welcome change to his hectic Monday-throughThursday schedule. Except for a lecture class in the morning,
Andrew is free to play a few hours of intramural Ultimate Frisbee
in the afternoon before meeting his friends for pizza and beer in
the evening.
Chapter Objectives
After reading this chapter, you will be
able to
1. Define metabolism and the role of
the cell during this process.
2. Distinguish between anabolic and
catabolic reactions and provide
examples of each.
3. Explain the role of adenosine
triphosphate (ATP) as an energy
source for cells.
4. Compare and contrast the major
metabolic pathways that carbohydrates, fatty acids, glycerol, and
amino acids follow to produce ATP.
5. Explain how metabolism changes
when you eat too many or not
enough kilocalories to meet your
energy needs.
6. Describe the metabolic process
of gluconeogenesis.
7. Explain how ketone bodies are
formed.
8. Describe the metabolism of alcohol.
9. Explain how the major hormones
help regulate the anabolic and
catabolic reactions of metabolism.
What Is Metabolism?
How does a kilocalorie from food transform into the energy required to throw a baseball, open a door, or think through a math equation? The answer can be summed up
in one word: metabolism.
Metabolism is the sum of all the chemical reactions that take place within the
10 trillion cells in the body. Some of these reactions generate energy by converting the
kilocalories in carbohydrates, protein, and fats into a more usable form. This energy
is produced anaerobically (without oxygen) or aerobically (with oxygen), depending
on the fuel that is available and the amount of oxygen in the cell.
In addition to energy, metabolic reactions also produce biological compounds
(such as nonessential amino acids) and intermediate substances that are needed to ensure that metabolism runs smoothly. Because the body constantly needs energy, metabolism never stops. The processes adapt and shift with changes in the environment,
whether youre in the middle of a meal or fasting during sleep.
Understanding how metabolism works is an important aspect of the study of nutrition. Learning about the process may seem daunting at first because there are numerous reactions involved, and the macronutrients use different metabolic pathways
to produce energy. With names like glycolysis, the TCA cycle, and the electron transport chain, the pathways can sound complex and intimidating. However, tackling each
pathway individually and comparing them to each other will help you understand
them more easily. Its not unlike assembling a jigsaw puzzle. Once the first pieces are
in place, the larger picture begins to take shape and the later pieces are easier to understand. In this chapter well discuss the individual pieces (pathways) of the greater
metabolic puzzle, then assemble them into the complete energy-making process
(Figure 8.1).
10. Describe the causes, diagnosis,

symptoms, and dietary treatments of the most common inborn errors of metabolism.
Clearly, Andrews energy needs vary

with his changes in schedule. But his
food intake doesnt always provide the
kilocalories he needs to match those energy requirements. In some cases, he
eats more kilocalories than he needs.
Luckily, his metabolism adjusts to these
changes in exercise and food intake by
storing excess kilocalories when he eats
more than he requires and breaking down
stored nutrients for energy when he
doesnt eat for long periods of time. Can
you guess how this works? Why do you
think Andrew is irritable on most weeknights? How does his
body adapt to the increase in kilocalorie intake on the other
days of the week?
In this chapter, we will learn about the bodys metabolism,
including how this process provides energy and adapts to the
day-to-day changes in dietary intake. We will also discuss what
can happen when metabolic processes fail to work properly.
Chapter 8 . Your Bodys Metabolism
Metabolism Takes Place Within Cells

The chemical reactions involved in energy production and storage take place within
the bodys cells. Even though different cells perform different metabolic functions,
their structure is similar (Figure 8.2). All cells have an outer envelope, the plasma membrane, that holds in the cells contents, and several specialized internal structures, called
organelles.
One particular organelle, the mitochondrion (plural: mitochondria), is referred
to as the powerhouse of the cell because it is the site of all aerobic metabolism. Other
than red blood cells, which produce energy anaerobically, almost all body cells contain mitochondria. Anaerobic metabolism takes place in the cytosol, or fluid portion
of the cell.
Other organelles also participate in metabolism. The ribosomes, for example, help
to manufacture proteins, and the smooth endoplasmic reticulum produces lipids used
by the organelles.1 Figure 8.2 illustrates a typical energy-producing cell.
The Liver Plays a Central Role

in Metabolism
The most metabolically active organ in the body is the liver. Once nutrients have been
absorbed, the liver is the first organ to metabolize, store, or send them through the
blood to other tissues. In previous chapters you learned that the proteins, carbohydrates, and fats in foods are digested and absorbed as amino acids, monosaccharides,
glycerol, and fatty acids, respectively. The metabolic processes in the liver convert them
into usable forms of energy, or into storage forms, such as glycogen or triglycerides.
The fate of each nutrient once it reaches the cells is illustrated in Figure 8.3.
Glycolysis
Acetyl CoA
TCA
Cycle
Electron
Transport Chain
Figure 8.1 Overview of Energy

Metabolism
The chemical reactions of metabolism include
glycolysis, the intermediate reaction of
pyruvate to acetyl CoA, the TCA cycle, and the
electron transport chain.
Plasma membrane
Cytosol, the fluid portion
of the cell, is involved in
anaerobic metabolism
Ribosomes
Nucleus
Smooth endoplasmic
reticulum
metabolism The sum of all chemical

reactions in the body.
metabolic pathway A sequence of
reactions that convert compounds from
one form to another.
Mitochondria play a key

role in aerobic energy
production
Figure 8.2 Metabolism Takes Place Within Cells

The mitochondrion is a metabolically active organelle located in the cytoplasm of a cell.
mitochondrion A cellular organelle that

produces energy from carbohydrates, proteins, and fats; pl. mitochondria.
cytosol The fluid portion of the cell
where anaerobic metabolism takes place.
What Is Metabolism?
Figure 8.3 The Metabolic Fate of Food

After the energy-containing nutrients have
been absorbed through the small intestine,
they can enter a metabolic pathway and be
converted to energy, or be stored as fat for
later use.
Proteins
Carbohydrates
Amino acids
Monosaccharides
Lipids
Glycerol
Fatty acids
Glycolysis
Acetyl CoA
TCA
Cycle
Electron
Transport Chain
Metabolism Follows Individual

Metabolic Pathways
Different nutrients will initially follow different pathways on their way to becoming
energy. For example, carbohydrates enter metabolism through a pathway called glycolysis, while the first step in metabolizing fats is beta-oxidation. Eventually, they all
converge in a pathway called the TCA cycle. Protein is used to a very limited extent to
produce energy because of its other specific roles in the body.
Metabolic pathways can involve only two to three reactions, or they can be much
more complex and require many more reactions to complete. As you follow the pathways in Figure 8.3, note the conversion from one compound to another.
Anabolic and Catabolic Reactions

Metabolism allows the body to
convert energy from foods into
energy needed for physical activity.
anabolic reactions Metabolic reactions

that combine smaller compounds into
larger molecules.
In general, there are two types of chemical reactions involved in metabolism: those
that need energy and those that produce energy (Figure 8.4). Anabolic reactions generally use energy to combine simpler molecules into larger, more complex ones. For
example, single amino acids combine to form larger proteins. Excess glucose molecules combine in a branched-chain structure to form glycogen, and excess fatty acids
attach to glycerol molecules and are stored as triglycerides in fat cells. These are all examples of anabolic reactions that require energy.
a Anabolic reactions use ATP

to combine smaller molecules,
such as glucose, into larger
compounds, such as glycogen,
and release small amounts
of heat.
Glucose
Glycogen
Anabolic
reaction
Catabolic
reaction
Glycogen
Glucose
Figure 8.4 Anabolic and Catabolic

Reactions
Metabolic processes involve both anabolic and
catabolic reactions.
b Catabolic reactions break

down larger molecules into
smaller compounds and release
energy in the form of ATP
and heat.
Catabolic reactions are the opposite of anabolic processes: They generate energy
to fuel anabolic reactions. Catabolic processes break down large molecules into simple structures that can be used for energy, recycled for their individual parts, or excreted. For example, larger glycogen molecules can be hydrolyzed to yield smaller
molecules of glucose, and triglycerides are disassembled to yield smaller fatty acids
and glycerol. The smaller glucose, fatty acid, and glycerol molecules are then transformed through energy metabolism to produce energy.
Enzymes and Hormones

Regulate Metabolism
Enzymes and their assistant coenzymes allow the chemical reactions of metabolism
to occur at fast enough rates to maintain normal body function. Nearly every metabolic reaction requires a different enzyme.
Anabolic and catabolic reactions can also be regulated by hormones. When the endocrine system detects a change in the concentration of nutrients, such as when blood
glucose levels rise, hormones are released that influence whether enzymes are activated
or turned offto control the metabolic pathways.For example,the hormone insulin lowers blood glucose levels by controlling the movement of glucose into the cells. Further,
within the cells, insulin controls the metabolism of the glucose. Three other hormones,
namely glucagon, epinephrine, and cortisol, can also influence metabolism and result in
an increase in blood glucose by stimulating glycogenolysis. Table 8.1 outlines the major
hormones controlling anabolic and catabolic reactions.
catabolic reactions Metabolic reactions that break large compounds into

smaller molecules.
Table 8.1
The Major Hormones That Control Metabolism

Hormone
Type of Reaction
Control of
Protein Metabolism
Control of
Carbohydrate Metabolism
Control of
Fat Metabolism
Insulin
Anabolic
Stimulates protein synthesis
Increases glycogen synthesis
Glucagon
Catabolic
Stimulates protein degradation
Stimulates glycogenolysis
Stimulates lipolysis
Epinephrine
Catabolic
No effect
Stimulates glycogenolysis
Stimulates lipolysis
Cortisol
Catabolic
Stimulates protein degradation
Stimulates gluconeogenesis
What Is Metabolism?
Can Energy Drinks Alter Your Metabolism?

In 2006, young adults in the United
States spent over $3 billion on energy
drinks, including brands such as Red
Bull, Monster, and Hype.1 Why are these
drinks so popular, particularly with
college-aged adults? The answer, at least
in part, is that many people believe that
energy drinks boost metabolism.
Energy Drinks Contain

Caffeine
Energy drinks contain a combination of
ingredients including caffeine and an assortment of amino acids, herbs, sugar,
and B vitamins. The main ingredient is
caffeine, a well-known central nervous
system stimulant that makes some people feel more alert and energized, and
others jittery. In addition to its stimulating
effects, caffeine has also been shown to
promote lipolysis,2 enhance the rate of
fatty acid oxidation, and decrease the
utilization of glycogen. In other words,
when you ingest caffeine, you burn more
fat to produce energy and spare
glycogen stores.3 Though this might
sound like an easy recipe for weight

loss, the reality is that consuming too
much caffeine can have negative health
effects. Until further research has been
conducted, caffeine should not be considered a weight-loss aid.
Herbs such as guarana and ginseng
are also often added to energy drinks. In
addition to adding extra caffeine to the
beverage (guarana can add 40 milligrams
of caffeine for every gram of guarana
added to the drink), these substances
may also enhance the effects of the
caffeine.
Side Effects of Caffeine

Though people vary in their responses to
caffeine, overall it is a strong stimulant,
and the amount of caffeine contained in
an energy drink is sufficient to boost
heart rate and raise blood pressure. In
some individuals, caffeine can cause
anxiety and diminish the ability to concentrate, as well as impact sleep and
cause insomnia. Whereas ingesting high
amounts of caffeine may help you stay
awake during an all-night study session,

your classroom performance is actually
more likely to suffer due to lack of adequate sleep.
Most people should limit caffeine intake to no more than 300 milligrams of
caffeine per day, the amount found in
three 8-ounce cups of coffee or four cans
of Red Bull (see table). This amount has
not been found to cause health concerns
for most individuals.
Though it was once known as a diuretic, caffeine does not appear to be
as dehydrating as researchers once
thought.4, 5 Caffeine does stimulate the
kidneys to excrete more water, but the
fluid intake from drinking the beverage
probably offsets the diuresis stimulated
by caffeine.
Energy Drinks and Alcohol

The rise in popularity of mixing energy
drinks with alcoholic beverages, such as
vodka, has been cause for concern in the
last decade.6, 7 Caffeine and alcohol affect
the central nervous system in opposite
Caffeine Content of Energy Drinks and Common Beverages

Beverage
SoBe No Fear
Serving
Size (oz)
Energy
(kcal/8 oz)
Caffeine
(mg/serving)
130
141.1
16
Other Ingredients
Taurine, inositol, ginseng, guarana, carnitine, arginine,
vitamins, minerals
SoBe Adrenaline Rush
8.3
135
76.7
Taurine, carnitine, inositol, ginseng, vitamins
Red Celeste
8.3
100
75.2
Vitamins, corn syrup
Amp
8.4
120
69.6
Taurine, guarana, panax, ginseng, maltodextrin
Red Bull
8.3
109
66.7
Taurine, inositol, vitamins
Red Bull Sugarfree
8.3
64.7
Taurine, inositol, aspartame, vitamins
Red Devil
8.4
80
41.8
Taurine, guarana, ginseng, Ginkgo biloba, vitamins
KMX
8.4
120
33.3
Yerba mat, ginseng, choline, guarana, vitamins
Coca-Cola Classic
12
140
34.0
High-fructose corn syrup
Pepsi
12
150
37.0
High-fructose corn syrup
Mountain Dew DMX
12
120
48.2
Ginseng, taurine, guarana, maltodextrin
Starbucks brewed coffee
12
140.0
Water
Tea (black)
12
45.0
Water
Energy drinks
ways: ethanol acts as a depressant, while

caffeine is a stimulant. The concern is
that combining alcohol with caffeine may
make you feel less intoxicated even
though your reaction time is impaired.
To address these concerns, researchers tested volunteers using a
double-blind study on motor coordination,
visual reaction times, and feelings of intoxication after drinking either alcohol,
alcohol mixed with a popular brand of
energy drink, or the energy drink alone.
The results suggested that drinking alcohol with an energy drink causes the same
level of intoxication as alcohol alone, but
the individual feels more energetic and
less impaired than if he had only consumed alcohol.8 The results also showed
that drinking an energy drink with alcohol
is likely to raise heart rate higher than
drinking either the alcohol or the energy
drink alone.9
Combining alcohol with caffeine is also
more likely to result in injury. A recent
study found that students who consume
energy drink cocktails are at double the
risk of injury, needing medical attention,
and driving with intoxicated drivers as
those who dont mix energy drinks with
alcohol.10
Blending alcohol with caffeine can also

have a negative impact on bone health.
Excessive consumption of either alcohol
or caffeine can reduce the mineralization
of bone. The combination of the two
could pose an increased risk for osteoporosis for both men and women.11
Because of the demonstrated negative
health effects of drinking high-caffeine
beverages with alcohol, individuals are
advised to abstain from this practice. As
with other caffeinated beverages, consumption of energy drinks should be limited so that no more than 200 to 300
milligrams of caffeine are consumed per
day. And as you learned in Chapter 7,
those who choose to drink alcohol are
advised to do so only in moderation. The
mix of energy drinks and alcohol can lead
to serious health consequences.
References
1. Worcester, S. 2007. Energy Drink Sales
Hit $3 BillionAt What Health Cost?
Millions of U.S. Teens Go for Their Buzz.
Pediatric News 41:1.
2. Servane, R., M. Ferruzzi, I. Cristiana,
J. Moulin, K. Mace, K. Acheson, and
L. Tappy. 2007. Effect of a Thermogenic
Beverage on 24-Hour Energy Metabolism
in Humans. Obesity 15:349355.
3. Acheson, K. J., G. Gremaud, I. Meirim,

F. Montigon, Y. Krebs, L. B. Fay,
L. J. Gay, P. Schneiter, C. Schindler, and
L. Tappy. 2004. Metabolic Effects of Caffeine in Humans: Lipid Oxidation or Futile
Cycling? American Journal of Clinical Nutrition 79:4046.
4. Armstrong, L. 2002. Caffeine, Body Fluidelectrolyte Balance, and Exercise Performance. International Journal of Sport
Nutrition and Exercise Metabolism,
12:189206.
5. Armstrong, L. E., A. C. Pumerantz, M. W.
Roti, D. A. Judelson, G. Watson, J. C.
Dias, B. Sokmen, D. J. Casa, C. M.
Maresh, H. Lieberman. 2005. Fluid, Electrolyte, and Renal Indices of Hydration
During 11 Days of Controlled Caffeine
Consumption. International Journal of
Sport Nutrition and Exercise Metabolism
15:252265.
6. Ferreira, S. E., M. T. de Mello, M. V.
Rossi, M. Souza-Formigoni. 2006. Effects
of Energy Drink Ingestion on Alcohol Intoxication. Alcoholism: Clinical and Experimental Research 30:598605.
7. Oteri, A., F. Salvo, A. P. Caputi, G.
Calapai. 2007. Intake of Energy Drinks in
Association with Alcoholic Beverages in a
Cohort of Students of the School of Medicine of the University of Messina.
Alcoholism: Clinical and Experimental Research 31:16771680.
8. Ferreira, et al. 2006. Alcoholism: Clinical
and Experimental Research.
9. Ferreira, S. E., M. T. de Mello, M. V. Rossi,
M. Formigoni. 2004. Does an Energy Drink
Modify the Effects of Alcohol in a Maximal
Effort Test? Alcoholism: Clinical and Experimental Research 28:14081412.
10. Wake Forest University Baptist Medical
Center. Energy Drink Cocktails Lead to
Increased Injury Risk, Study Shows.
Science Daily. www.sciencedaily.com/releases/2007/11/071104191538.htm. Accessed July 2007.
11. Hansen, S. A., A. R. Folson, L. H. Kushi,
and T. A. Sellers. 2002. Association of
Fractures with Caffeine and Alcohol in
Postmenopausal Women: The Iowa
Womens Health Study. Public Health
Nutrition 3:253261.
Can Energy Drinks Alter Your Metabolism?
The Take-Home Message Metabolism is the sum of all metabolic

processes that occur in cells. Most of these reactions take place within the mitochondria. Metabolic processes follow specific pathways that use energy to
build new substances through anabolic reactions or produce energy by breaking molecules apart through catabolic reactions. Enzymes catalyze the reactions involved in metabolism, and hormones, including insulin, glucagon,
epinephrine, and cortisol, regulate these reactions.
How Does the Body

Fuel Metabolism?
All body actions require energy, whether youre running a marathon or lying in bed.
Further, the more difficult the action, the more energy the body needs to fuel it. For
example, your body must produce much more energy to lift a 50-pound bag of dog
food than to lift a 5-pound bag of flour. You know by now that the source of fuel for
all this energy production is food.
However, before your body can use the energy in the cereal, fruit, and toast you
ate for breakfast, it must first disassemble the macronutrients, build them into new
compounds, and transform them into a high-energy molecule called adenosine
triphosphate, or ATP.
The Importance
of Adenosine Triphosphate
adenosine triphosphate (ATP) A

high-energy molecule composed of adenine, ribose, and three phosphate molecules; cells use this to fuel all biological
processes.
adenosine diphosphate (ADP) A nucleotide composed of adenine, ribose, and
two phosphate molecules; it is formed
when one phosphate molecule is removed
from ATP.
creatine phosphate (PCr) A compound that provides a reserve of phosphate to regenerate ADP to ATP.
10
ATP is the only source of energy that can be used directly by cells. The process of disassembling food to create ATP actually requires some ATP to convert the energy into
more ATP. (In other words, you have to spend ATP to make ATP.) The cells then use
that ATP to fuel metabolic processes.
ATP is made of adenine (a nitrogen-containing compound), ribose (a fivecarbon sugar), and three phosphate groups (which contain phosphorus and oxygen).
The energy is stored in the bonds that connect the phosphate groups to each other.
As Figure 8.5 illustrates, when you need energy, one of the bonds connecting the
phosphate groups is hydrolyzed, which releases one inorganic phosphate plus a
tremendous amount of energy. The new molecule that is formed is called adenosine
diphosphate, or ADP.
At any given moment, cells only have 3 to 5 seconds worth of ATP available for
immediate use. Therefore, the body must continually produce ATP to provide a constant supply of energy.
Creating ATP from ADP

and Creatine Phosphate
Regenerating ATP from ADP requires a source of inorganic phosphate. As illustrated
in Figure 8.5, the inorganic phosphate produced from the initial breakdown of ATP
is one source. However, this provides only 8 to 10 seconds of energy. Another source
of inorganic phosphate is creatine phosphate, also called phosphocreatine, or PCr.
PCr is a high-energy compound formed in muscle cells when creatine (an amino acid
Adenine
Phosphate
bond
O
P
1 When you need energy, your body hydrolyzes one of

the phosphate bonds, releasing one phosphate and a
tremendous amount of energy.
Phosphates
Ribose
Adenosine triphosphate
ATP
Pi
Inorganic
phosphate
Adenine
O
P
2 With the release of one phosphate from ATP, a new

molecule with only two phosphates is formed, adenosine
diphosphate, or ADP. A phosphate group is added back
to ADP to reform ATP during catabolism.
Phosphates
Ribose
Adenosine diphosphate
ADP
Figure 8.5 ATP to ADP
structure found in foods and produced in the body) combines with inorganic phosphate. This phosphate can be released from creatine phosphate and added to ADP to
form ATP. In addition, when the phosphate bond is broken, energy is released, which
provides the fuel needed to restore ATP. You may have heard of the supplement creatine monohydrate, which is marketed to athletes to maximize their PCr stores. Research shows that supplemental creatine can increase performance of short-duration,
high-intensity activities but may also have side effects.2 Well discuss this more in
Chapter 16.
Once the available ATP and creatine phosphate in the muscle cell is exhausted,
more ATP must be produced through anaerobic and aerobic metabolic processes.
Anaerobic metabolism produces more ATP per minute than does aerobic metabolism, but it is very limited in its use (it only provides about 1 to 1.5 minutes of
maximal activity). Activities that primarily involve anaerobic metabolism are highintensity, short-duration activities such as sprinting or heavy weight lifting. Aerobic
metabolism produces less ATP per minute than anaerobic metabolism, but it can continue indefinitely. Low-intensity, long-duration activities, such as walking or slow jogging, primarily involve aerobic metabolism. When the demand for ATP is greater than
the rate at which metabolism can produce it, the activity slows down or stops completely. This is one reason why individuals who lift weights have to rest between sets;
it gives the body time to form more ATP to be used for the next set of lifts.
The transformations that convert energy in protein, carbohydrate, fat, and alcohol into ATP are tightly integrated and somewhat complex. To learn this material, well
break down these integrated processes according to the macronutrient being metabolized. Well begin with carbohydrate metabolism.
The Take-Home Message
ATP is the energy the body uses to fuel all

its metabolic reactions. No ATP is stored, thus ATP must be formed from ADP
and inorganic phosphate (which can be donated by creatine phosphate), or
produced during anaerobic or aerobic metabolism.
How Does the Body Fuel Metabolism?
11
How Do Carbohydrates
Provide Energy?
Carbohydrate metabolism, and specifically glucose metabolism, is the backbone of energy production because of its importance as an energy source for the brain and red
blood cells. Glucose is unique in that it can generate ATP both anaerobically and aerobically. Once glucose enters the cell, it is transformed into energy through four metabolic pathways: glycolysis, the intermediate reaction pyruvate to acetyl CoA, the
tricarboxylic acid (TCA) cycle, and the electron transport chain.
Step 1: Glycolysis
From Glucose to Pyruvate
The first step in forming ATP from glucose begins with glycolysis (glyco glucose,
lysis break apart). As you follow this metabolic pathway, illustrated in Figure 8.6,
track the carbons through the process from beginning to end.
Glycolysis is a ten-step catabolic pathway that takes place in the cytosol of the cell.
It begins with one, six-carbon glucose molecule and ends with two, three-carbon molecules of pyruvate and two molecules of ATP.3 As you can see in Figure 8.6, the initial
step requires ATP. In this reaction, a phosphate is transferred from ATP to the sixth
carbon of glucose as the glucose enters the cell, forming glucose 6-phosphate and ADP.
Once glucose 6-phosphate is formed, it continues through nine more reactions until
the pathway is complete and pyruvate is formed.
In addition to glucose, other monosaccharides, including fructose and galactose,
can be used to produce ATP, but they enter glycolysis at different locations. Most of
the fructose you eat, whether part of the disaccharide sucrose or in fruit, is metabolized by the liver for energy. It enters glycolysis through fructose 6-phosphate after
seven metabolic steps. Galactose goes through four metabolic steps before it enters
glycolysis at glucose 6-phosphate.
In addition to ATP, glycolysis also generates hydrogen ions (H). The hydrogen
ions and their electrons are picked up by coenzymes made from the B vitamin niacin
and transported to the electron transport chain.
In summary, at the end of glycolysis, what began as one six-carbon molecule of
glucose has produced two three-carbon molecules of pyruvate, two ATP, two coenzyme molecules, two hydrogen ions (which enter the electron transport chain), and
two molecules of water. Now lets continue down the metabolic pathway with the newly
formed pyruvate.
glycolysis The breakdown of glucose;

for each molecule of glucose, two molecules of pyruvate and two ATP molecules
are produced.
pyruvate A three-carbon molecule
formed from the oxidation of glucose during glycolysis.
acetyl CoA A two-carbon compound
formed when pantothenic acid combines
with acetate.
12
Step 2: The Intermediate Reaction

Pyruvate to Acetyl CoA
When cells contain an ample supply of oxygen, pyruvate continues down the energy
pathway to form acetyl CoA, the gateway molecule for the TCA cycle. In the presence
of oxygen, the two molecules of pyruvate formed during glycolysis enter the mitochondria, where they each lose a carbon and gain a molecule of coenzyme A. Coenzyme A (which contains the B vitamin pantothenic acid) attaches to the remaining two
carbons from pyruvate to form acetyl CoA. Thus a three-carbon pyruvate molecule is
changed to a two-carbon acetyl CoA. The third carbon combines with oxygen to form
Acetyl CoA
Glucose
C C C C C C
Glycolysis
1 A phosphate group is added to glucose to

form glucose 6-phosphate. ATP is used
in this reaction.
ATP
ADP
C C C C C C
Glucose 6-phosphate
C C C C C C
Fructose 6-phosphate
Fructose 1,6-bisphosphate
TCA
Cycle
2 Glucose 6-phosphate is rearranged to form a

new compound called fructose 6-phosphate.
Electron
Transport Chain
3 One phosphate is added to fructose

6-phosphate to create fructose
1,6-bisphosphate. 1,6 indicates where the
phosphates were added to the carbon chain.
ATP is used in this reaction.
ATP
ADP
C C C C C C
4 Fructose 1,6-bisphosphate is broken down to

glyceraldehyde 3-phosphate (G3P) and
dihydroxyacetone phosphate (DHAP).
5 DHAP is rearranged to create another

molecule of G3P.
Dihydroxyacetone
phosphate
P
6 Two phosphates are added to each G3P to

form two molecules of 1,3-bisphosphoglycerate
NAD+. Two molecules of NAD+ are formed
in the process.
Glyceraldehyde
3-phosphate
C C C
C C C
2 Coenzymes
2 Coenzymes
7, 8, 9 In the next three steps, two ATP and two

molecules of water are formed.
10 Two molecules of pyruvate and two molecules

of ATP are formed in the final step of glycolysis.
H+
e-
C C C
C C C
ADP
ADP
ATP
ATP
H2O
C C C
C C C
ADP
ADP
ATP
ATP
1,3-bisphosphoglycerate
H2O
2-phosphoenolpyruvate
C C C
C C C
Pyruvate
Figure 8.6 Step 1: Glycolysis

Glycolysis is a ten-step process in the cytosol of the cell that converts glucose to pyruvate.
How Do Carbohydrates Provide Energy?
13
2 Coenzymes
Glycolysis
C C C
C C C
Acetyl CoA
TCA
Cycle
Electron
Transport Chain
2 Pyruvate
CoA CoA
2 Coenzymes
C O2 C O2
2 Coenzymes
C C
CoA
C C
CoA
Figure 8.7 Step 2: The Fate of Pyruvate

At the end of glycolysis, two molecules of
pyruvate are formed for every molecule of
glucose. These three-carbon molecules can be
converted to acetyl CoA and enter the TCA
cycle or be transformed into lactate.
Lactate
H+
e-
2 Acetyl CoA
carbon dioxide, and is expelled through

the lungs as waste. This step is illustrated
in Figure 8.7.
Once acetyl CoA is formed it can either continue down the pathway to enter
the TCA cycle (if ATP is scarce) or it can
be transformed into a fatty acid and stored
as fat (if ATP is abundant). When ATP is
scarce, acetyl CoA enters the TCA cycle
(step 3) where hydrogen ions are produced
for use by the electron transport chain
(step 4). These last two steps are discussed
in detail later in this chapter.
Pyruvate to Lactate
When mitochondria lack sufficient oxygen, such as during intense exercise, pyruvate
is reduced to lactate to prevent the buildup of hydrogen ions in the cell. In some situations, such as during strenuous exercise, lactate is not produced fast enough to keep
up with the production of hydrogen ions. Under these conditions the hydrogen ions
build up, which reduces the pH in the muscle cell. Contrary to popular belief, it is the
buildup of hydrogen ions, not lactate, that produces the uncomfortable burningsensation in the muscles after exercise.
Lactate diffuses out of the cell into the blood, where it is transferred to the liver.
Once in the liver, enzymes convert the lactate back to pyruvate. The pyruvate is then
transformed into glucose through the Cori cycle (Figure 8.8) and released back into
the blood, where it is picked up by the muscle to begin glycolysis over again.4
The Take-Home Message Carbohydrates provide energy to cells

through the process of glycolysis, the backbone of metabolism. Once glucose
enters the cell, it undergoes a ten-step conversion to yield two molecules of
pyruvate, two ATP, two coenzymes, two hydrogen ions, and two molecules of
water. Pyruvate can be reduced to lactate during anaerobic metabolism, or it
can be converted to acetyl CoA during aerobic metabolism before it enters the
TCA cycle.
Chemistry Boost
lactate A three-carbon compound generated from pyruvate when mitochondria

lack sufficient oxygen.
Cori cycle A series of metabolic reactions in liver cells that convert lactate to
glucose; also called gluconeogenesis.
14
We obtain energy during metabolism by oxidation/reduction reactions (also called

redox reactions), which involve the transfer of electrons. Redox reactions happen in
sets in that when an oxidation reaction occurs (one molecule loses an electron) another
molecule is reduced (gains an electron).
During glycolysis, glucose is oxidized to pyruvate by the coenzyme form of the B
vitamin niacin (NAD), which acts as the oxidizing agent. Glucose loses an electron to
NAD which in turn is reduced to NADH.
Here is the oxidation/reduction reaction in glycolysis:
2 NAD glucose 2 pyruvate 2 NADH 2 H
Figure 8.8 The Cori Cycle

The Cori cycle takes place in the liver and
converts lactate to glucose.
Liver
Glu
co
se
Glucose
Glycogen
Artery
Pyruvate
Lactate
Glucose
Pyruvate
Lactate
Vein
Lac
t a te
Muscle
How Does Fat

Provide Energy?
Dietary fat (triglycerides) is a more concentrated source of kilocalories than either carbohydrates or proteins, and yields about six times more energy. Recall from Chapter 5
that triglycerides consist of a glycerol backbone and three fatty acids and are stored in
adipose tissue until they are needed for energy production. Both glycerol and fatty acids
can be used for fuel, although glycerol produces very little energy.
Triglycerides Are Broken Down

into Fatty Acids and Glycerol
Before triglycerides can be used for fuel, they are hydrolyzed to fatty acids and glycerol during lipolysis. An enzyme in the adipose tissue catalyzes the reaction, and the
activity of this enzyme is stimulated by the hormone glucagon when the diet contains
very little carbohydrate, or by the adrenal hormones epinephrine or cortisol when an
individual is under stress. Once the fatty acids and glycerol are free, they are released
into the blood and taken up by various tissues, including the muscle and the liver.
Fatty acids and glycerol enter the metabolic pathway differently (Figure 8.9). Glycerol is considered glucogenic (gluco glucose, genic forming) and can be used to
produce glucose. Fatty acids are not glucogenic but they can be used to produce ketone bodies (which are used as backup fuel for the brain and nerve function when glucose is limited), and are therefore ketogenic (keto ketone, genic forming).
glucogenic Molecules that can be transformed into glucose.

ketogenic Molecules that can be transformed into ketone bodies.
How Does Fat Provide Energy?
15
H
H
Fatty acid
O
H
Fatty acid
O
H
Fatty acid
H
Triglyceride
ATP
C
Glycolysis
C
C
C
Fatty acid
C C C
Beta-oxidation
TCA
Cycle
C
CoA
C C C
DHAP
Glycerol
C C C
CoA CoA
Acetyl CoA
ADP
G3P
Coenzyme
C
Coenzyme
H+
C C C
e-
Pyruvate
Shorter fatty acid

Electron
Transport Chain
1 Glycerol is first converted

to DHAP before it can enter
glycolysis.
Coenzyme
Coenzyme
H+
C C
CoA
e-
Acetyl CoA
2 Fatty acids are metabolized

for energy through
beta-oxidation, producing
acetyl CoA, which can enter
the TCA cycle.
Figure 8.9 Using Fat for Energy

Stored triglycerides can be used for energy after first hydrolyzing the fatty acids from the glycerol
backbone.
Glycerol to Pyruvate
The glycerol released from the triglyceride molecule is taken up by the liver and either
converted to glucose through gluconeogenesis or enters glycolysis to produce ATP and
pyruvate, depending on the bodys need for glucose.
During periods of fasting, the need for blood glucose dramatically increases, so
more glycerol will be converted to glucose, which can then enter the bloodstream to
maintain blood glucose levels.
Fatty Acids to Acetyl CoA
beta-oxidation A series of metabolic

reactions in which fatty acids are oxidized
to acetyl CoA; also called fatty acid
oxidation.
16
Fatty acids arent glucogenic and are instead converted to acetyl CoA to be oxidized in
the mitochondria for energy. Just as you put on a coat to prepare to step outside on a
cold day, fatty acids are prepared or activated in the cytosol before they cross into the
mitochondria. This step, which requires ATP, involves adding coenzyme A to the carboxylic end of the fatty acid chain, forming acyl CoA. Long-chain fatty acyl CoA can
then easily cross the mitochondrial membrane with the help of a carrier molecule.
The fatty acid is disassembled inside the mitochondrion by a series of chemical
reactions called beta-oxidation. During beta-oxidation the fatty acid is taken apart
two carbon fragments at a time, beginning at the carboxyl end of the molecule. The
two-carbon pairs are joined by another CoA and converted to acetyl CoA. This process
continues, forming a new acetyl CoA and a shorter fatty acid chain until all of the carbons have been oxidized.
As each pair of carbons is cleaved off from the fatty acid chain, hydrogen and electrons are released. The hydrogen atoms are picked up by two coenzyme hydrogen carriers, which then unload the hydrogen atoms in the electron transport chain.
The Relationship
of Triglycerides to Glucose
During periods of fasting or starvation, or for those with diabetes mellitus, gluconeogenesis becomes an essential metabolic pathway because the brain and nerves prefer to use glucose as fuel, and the red blood cell can only use glucose for energy. When
the diet is low in carbohydrates, cells turn to other sources to produce the necessary
glucose. One such source is the glycerol in the triglycerides stored in adipose tissue.
As mentioned earlier, only the glycerol portion of the triglyceride molecule is
glucogenic. Glycerol is taken up by the liver and enters gluconeogenesis to produce
glucose. When fatty acids are converted to acetyl CoA, the action is irreversible and
they are committed to enter the TCA cycle. Thus, only the glycerol portion of the
triglyceride is involved in maintaining blood glucose levels.
The Take-Home Message Whereas both the glycerol and fatty acid
portion of triglycerides can provide energy, fatty acids are the most concentrated
source. Fatty acids break down into two-carbon fragments to be converted into
acetyl CoA. Glycerol can also produce energy by entering glycolysis. Glycerol
is considered glucogenic because it can form glucose through gluconeogenesis and thus help maintain blood glucose levels. Fatty acids are ketogenic and
cannot be used to form glucose.
How Does Protein

Provide Energy?
As you learned in Chapter 6, the most important function of amino acids is to build
proteins. However, when the diet contains more protein than you need, the excess can
be used for energy production, converted to glucose, or stored as fat. Amino acids are
also used to a limited extent as a source of energy, especially when the diet is low in
kilocalories or carbohydrates. Regardless of the metabolic fate of protein, if the amino
acids are not used for protein synthesis, their amine groups are removed through
deamination (see Chapter 6). The remaining carbon skeleton is converted to other
compounds such as glucose (through gluconeogenesis), pyruvate, or TCA cycle intermediates, which can be metabolized for energy.
Of the twenty known amino acids, six amino acids are considered either only ketogenic (leucine and lysine) or both ketogenic and glucogenic (isoleucine, tryptophan,
phenylalanine, and tyrosine).5 Ketogenic amino acids generate acetyl CoA and can be
changed into either fatty acids or ketone bodies, depending on the bodys requirements. The other fourteen amino acids are glucogenic because they can be transformed
into pyruvate and other TCA cycle intermediates that enter gluconeogenesis and produce glucose. These conversions are shown in Figure 8.10 on the next page.
Amino Acids to Acetyl CoA

Whether amino acids are classified as ketogenic or glucogenic, they are all eventually
transformed to either acetyl CoA or other TCA molecules if they are to be used for
energy. Ketogenic amino acids are converted to acetyl CoA, while the glucogenic amino
acids are first degraded to pyruvate and then converted to acetyl CoA before entering
How Does Protein Provide Energy?
17
C C C C C C
Glucose
C C C
Pyruvate
Glycolysis
NH2
NH2
C C C
a Glucogenic amino acids are

converted to pyruvate and then
transformed into glucose through
gluconeogenesis.
Acetyl CoA
NH2
Coenzyme
C O2
TCA
Cycle
Coenzyme
NH2
C C C
C C
H+
e-
CoA Acetyl CoA
C
NH2
Electron
Transport Chain
NH2
b Ketogenic amino acids are

converted to acetyl CoA, which can
either be transformed into fatty acids
and stored as a triglyceride in
adipose tissue or enter the
TCA cycle.
NH2
TCA
Cycle
C C C C
NH2
c Some amino acids can enter the

TCA cycle directly.
Figure 8.10 Glucogenic and Ketogenic Amino Acid Metabolism
the TCA cycle. Remember that acetyl CoA cannot be used to make glucose, so once
these amino acids are transformed, they are committed to continue through the energy pathway or be converted to fatty acids or ketone bodies.
Amino Acids to Glucose

Glucogenic amino acids are a major source of blood glucose when the diet is lacking
in carbohydrate. The amino acids used by cells to make glucose come either from food
or from the breakdown of proteins in muscle. After these amino acids have been deaminated, they are transformed into pyruvate or one of the TCA cycle compounds.
Amino acids from protein can be used to

produce energy and glucose or converted to fatty acids and stored as a triglyceride. After they have been deaminated, the remaining carbon skeletons can
be transformed into pyruvate, acetyl CoA, or TCA cycle compounds. Glucogenic amino acids can also be converted to glucose when the diet lacks adequate carbohydrates.
Where Do the
Macronutrients
Come Together?
Regardless of the metabolic road that carbohydrates, proteins, and fats follow, they eventually all arrive at the same destination: acetyl CoA. We refer to acetyl CoA as the gateway molecule for aerobic metabolism because all energy-producing nutrients
glucose, amino acids, fatty acids, glyceroland alcohol are usually converted to acetyl
CoA before entering the TCA cycle.
18
Step 3: The Tricarboxylic

Acid (TCA) Cycle
The function of the TCA cycle is to gather electrons from the carbons in the energy
nutrients, rather than to directly produce ATP (although a small amount of energy is
produced in a similar high-energy compound called GTP). Remember that most of
the energy in the original glucose molecule is now trapped in the bonds of acetyl CoA.
During the TCA cycle, this stored energy is transferred to two coenzyme hydrogen ion
carriers to be released in the electron transport chain.
One molecule of acetyl CoA enters the cycle at a time. The first step is to remove
the CoA and combine the two remaining carbons with a four-carbon molecule called
oxaloacetate. Together, oxaloacetate and acetyl CoA form a new six-carbon compound
called citrate. The cycle continues with seven more reactions, ending with oxaloacetate
as the last molecule formed at the end of every turn of the TCA cycle. This brings us back
to the beginning of the cycle. Youll notice as you track the carbons in Figure 8.11 that
for every acetyl CoA that enters the TCA cycle, two carbons are lost as CO2.
oxaloacetate The starting molecule for

the TCA cycle.
Pyruvate
C C C
Glycolysis
C
C C
Acetyl CoA
CoA
Acetyl CoA
CoA
C OOH
C
C OOH
TCA
Cycle
Coenzyme
H+
e-
C
C OOH
C OOH
Coenzyme
8
Electron
Transport Chain
C C OOH
Oxaloacetate
Citrate
C OOH
C OOH
C C OOH
C OOH
C OOH
Coenzyme
TCA Cycle
H2O
H+
Coenzyme
+ CO2 e-
C OOH
C
C OOH
Coenzyme
HOO C
Coenzyme
C OOH
CoA
6
H+
4
C OOH
C OOH CoA
e-
C
Coenzyme
H+
Coenzyme
+ CO2 e-
C OOH
GTP
ADP
GDP
CoA
ATP
Figure 8.11 Step 3: The TCA Cycle

(1) The TCA cycle begins with oxaloacetate combining with acetyl CoA to form citrate. (28) The
cycle continues through seven more steps, changing the molecules and releasing hydrogen
atoms. Pyruvate can provide some oxaloacetate as a starting molecule for the cycle.
Where Do the Macronutrients Come Together?
19
transamination The transfer of an

amino group from one amino acid to an
alpha-keto acid to form a new nonessential
amino acid.
alpha-ketoglutarate A compound that
participates in the formation of nonessential amino acids during transamination.
alpha-keto acid The compound that is
formed after an amino acid has been
deaminated.
electron transport chain The final
stage of metabolism when electrons are
transferred from one complex to another,
resulting in the formation of ATP and water.
avoproteins Protein complexes that
move electrons down the electron transport chain; they contain the B vitamin
riboflavin.
cytochromes Protein complexes that
move electrons down the electron transport chain; they contain the minerals iron
and copper.
In addition to the two carbons, eight hydrogen atoms and their electrons are removed
during each turn of the TCA cycle. For example, in the third step of the cycle, a hydrogen
atom and electron is grabbed by a coenzyme carrier. Two more coenzymes and hydrogen
ions are formed in step 4 and in the final step in the cycle. In total, for each turn of the TCA
cycle, three molecules of coenzymes are released, along with carbon dioxide and water.
The TCA Cycle Provides Precursors

for Transamination
The TCA cycle also provides the starting material for creating nonessential amino acids
through transamination (trans transfer, amine amino group). Two important molecules, pyruvate (formed during glycolysis) and alpha-ketoglutarate (from the TCA cycle), can provide the necessary carbon skeletons to make a nonessential amino acid.
Recall that all amino acids must have an amino group (NH2). Thus, the first step
in forming nonessential amino acids is to transfer the amino group from an existing
amino acid to a compound called an alpha-keto acid (such as alpha-ketoglutarate),
which forms a new amino acidin this example, the amino acid glutamate. The newly
formed alpha-keto acid can then enter the TCA cycle to be used as an energy source.
Figure 8.12 illustrates this process.
Step 4: The Electron Transport Chain
The primary purpose of the electron transport chain is to assemble the majority of
the ATP that cells need to fuel the bodys actions. In fact, about 90 percent of the ATP
you use every day for energy, growth, and maintenance is generated during this final
stage of energy metabolism.6 This step is illustrated in Figure 8.13.
The electron transport chain is comprised of a series of protein complexes located
in the inner mitochondrial membrane. These protein complexes act as carrier molecules to transport the electrons generated during glycolysis, the TCA cycle, and fatty
acid oxidation along the chain. The electrons, which are carried to the chain by coenzymes, are passed from one protein complex to the next until they reach oxygen. At
the end of the chain, oxygen accepts the electron and binds with two molecules of hydrogen to form water. You can think of this process as being similar to a bucket brigade
in a fire. If one person in the brigade drops the bucket, the entire process slows down.
Likewise, if one electron is dropped during the electron transport chain, the production of ATP is slowed.
As the electrons are passed along the chain,the protons separate from the hydrogen atoms in the coenO H H NH2 O
O H H O O
zymes and are pumped out of the inner mitochondria
C C C C C
C C C C C
OH
HO
HO
OH into the intermembrane space. As the protons accumulate, they are forced back across the mitochondrial
H H H
H H
membrane. For every pair of hydrogen ions that crosses
Glutamic acid
Alpha-ketoglutaric acid
+
the cell membrane, one ATP is formed. The ATP is now
ready to be used for energy.
The protein complexes that transfer the electrons
O H O O
O H NH2 O
through the electron transport chain are classified as
C C C C
C C C C
HO
OH
HO
OH
flavoproteins, which contain the B vitamin riboflavin,
and cytochromes, which contain the minerals iron and
H
H H
Oxaloacetate acid
Aspartic
acid
copper. If you are iron deficient, the cytochromes are
+
Figure 8.12 Transamination
less able to pass the electrons along the chain to comNonessential amino acids can be formed by the transfer of an amino group (NH2)
plete the production of ATP. This is one of the reasons
from an amino acid, such as glutamic acid, to a keto acid, such as oxaloacetate,
forming a new amino acid.
someone with inadequate iron intake will feel tired or
20
High H+ concentration
Glycolysis
H+ H+
H+ H+ H+ H+ H+ H+
H + H+
H+ H+
Outside
of cell
Acetyl CoA
e-
e-
e-
e-
e-
Inner
mitochondrial
membrane
e-
TCA
Cycle
1 Coenzyme
Electron
Transport Chain
H+
H+ H+
e-
O2 + H+
H+
ATP
Coenzyme
Low H+ concentration
1 Hydrogen and electrons are delivered

to the mitochondrial membrane from the
TCA cycle by coenzymes.
ATP
synthase
2 As the electrons are passed down the

electron transport chain, hydrogen atoms
cross the mitochondrial membrane.
H2O
ATP
Inside
of cell
ATP
3 Hydrogen atoms are forced back

across the membrane through the ATP
synthase complex to produce ATP.
Figure 8.13 Step 4: The Electron Transport Chain
Table 8.2
The Metabolic Fate of Energy-Producing Nutrients
Nutrient
Produces
ATP?
Can
Produce
Glucose?
Can Be Used in
Transamination
(to produce
amino acids)?
Excess Can
Be Stored
as Fat?
Glucose
Yes
Yes
Yes
Yes
Amino acid
Yes
Yes
Yes
Yes
Fatty acid
Yes
No
No
Yes
Glycerol
Yes
Yes
Yes
Yes
Alcohol
Yes
No
No
Yes
fatigued. This illustrates the point that though vitamins and minerals do not provide energy, they are essential for energy production in the body.
Table 8.2 summarizes the role of individual nutrients in producing ATP, glycogen, nonessential amino acids, and fat, and Figure 8.14 on the next page provides a
detailed overview of all four stages of metabolism. Look at the figure closely; can you
describe whats happening in each stage?
ndrew snacks on high-carbohydrate and high-fat foods during
his afternoons on Mondays through Thursdays. What is the
metabolic fate of these carbohydrate and fat kilocalories? What
metabolic pathways is Andrew using to metabolize these
kilocalories? Would you expect Andrew to produce lactate as he
sits in lecture and works in the laboratory?
Where Do the Macronutrients Come Together?
21
The Take-Home Message All of the energy nutrientscarbohydrates,

proteins, and fatscome together in the gateway molecule acetyl CoA. Once
acetyl CoA is formed, it combines with oxaloacetate to form citrate in the first
step of the TCA cycle. One turn of the TCA cycle produces two coenzymes,
CO2, and a small amount of energy in the form of GTP. The electrons from hydrogen atoms in coenzymes enter the electron transport chain, where they are
passed along the chain by protein complexes. During this process, the protons
are used to form ATP and the electrons join with oxygen to make water.
Figure 8.14 Overview of Energy

Metabolism
The chemical reactions of metabolism convert
energy nutrients into ATP, carbon dioxide, and
water.
Proteins
Carbohydrates
Amino acids
Monosaccharides
Fats
Glycerol
Fatty acid
C
C C C
C
C
C
C
C
Glycolysis
C C C C C C
Glucose
Coenzyme
2 Coenzymes
NH2
NH2
C C C
CoA
H+
H+
e-
eC C C
C C
Pyruvate
CoA
NH2
CoA
Coenzyme
H+
eCoenzyme
C O2
NH2
C
C
Acetyl CoA
C
C C C
C C
CoA
NH2
CoA
NH2
NH2
Coenzyme
H+
Coenzyme
eTCA
Cycle
C C C C
e-
C O2
C O2
NH2
Coenzyme
H+
Coenzyme
e-
Electron Transport Chain

2
H+
2 H+
2 eCoenzyme
H+
e-
2 H+
2 e-
2 H+
2 e-
2H + O2
H2O
22
H+
ATP
H+
e-
H+
e-
What Happens if You

Eat Too Much?
There are occasions when we overeat and consume more kilocalories than we need.
Family gatherings, vacation meals, or even just weekend social events can be times
when we eat more kilocalories from fat, carbohydrate, protein, and alcohol than we
use for energy. Luckily, metabolism adjusts to either provide energy for immediate use
or store it for later, depending on your energy needs and intake.
Immediately after eating a meal, the body uses glucose as the primary source of
energy. Later, when you need energy during sleep, between meals, or when youre too
busy to eat, your body will use the glucose stored as glycogen, and the fatty acids and
glycerol stored in triglycerides, for fuel.
When we eat too much, our metabolism favors anabolic reactions for the sake of
storing the excess kilocalories. For instance, if you eat excess protein, the excess is converted to fatty acids and stored as a triglyceride. If you overconsume carbohydrates,
the anabolic reactions include converting the excess carbohydrates to glycogen. Once
the glycogen stores are full, carbohydrates are converted to fatty acids.
Lets take a closer look at Figure 8.15, which illustrates these anabolic and catabolic pathways.
Figure 8.15 Metabolism Adapts during Feasting or Fasting
Carbohydrates
Proteins
Lipids
Liver
Liver
Glycogen
Glucose
Glucose
Glycogen
Ketones
Muscle
Glycogen
Proteins
Energy
Energy
Muscle
Glycogen
Proteins
Glucose
Amino
acids
Energy
Fatty
acids
Energy
Energy
Fat cells
Fat cells
Fat
1 During times of plenty, anabolic reactions are favored by

metabolism. Excess carbohydrates are stored as glycogen in the
liver and muscle, or stored as fat in the adipose tissue. Protein is
used for building body proteins, with the excess converted to fat
and stored. Excess dietary fat is also stored in adipose tissue.
2 Metabolism shifts during fasting to catabolic reactions, which

result in liver glycogen providing blood glucose; muscle glycogen
is used for fuel by the muscles; adipose tissue releases fatty
acids to be transformed into ketone bodies in the liver and used
by the brain as fuel; body proteins are converted to glucose.
What Happens if You Eat Too Much?
23
Carbohydrate Is Stored as Glycogen

Although glucose is essential to red blood cells and the central nervous system, neither of these tissues can convert glucose to its storage forms, and both burn glucose
readily. The red blood cells dont have mitochondria, which means that they can only
use glucose anaerobically. The central nervous system cant store glucose as glycogen
nor can it convert excess glucose to fat. The liver and muscles, however, can convert
excess glucose to glycogen.
Remember that dietary glucose arrives first at the liver from the portal vein. If glucose levels are high in the liver, glucose can be converted to glycogen through glycogenesis, or it can circulate to other tissues. Enzymes in the muscle can also convert
excess glucose to glycogen. The body has a limited ability to store glycogen, however,
and only about 1 percent of body weight is in the form of glycogen.
Liver glycogen plays an important role in maintaining glucose homeostasis. When
intake of dietary carbohydrate is low, blood glucose levels drop. The glycogen stored
in the liver can be converted to blood glucose through glycogenolysis. However, about
12 to 18 hours after eating, liver glycogen levels are nearly depleted.
Even though muscle has a larger storage capacity for glycogen, it lacks the enzyme that can release glucose into the blood. In essence, glucose is trapped in the
muscle to be used for energy or stored as glycogen and is not used to maintain blood
glucose levels.
Fatty Acid Synthesis

The metabolic pathway to store dietary fat requires little energy (only about 5 percent)
and only a few steps; therefore dietary fat is more easily stored as body fat than dietary
carbohydrate or protein. Carbohydrates, in contrast, are first stored as glycogen and
only after those stores are full and energy needs are met will carbohydrates undergo
transformation to a triglyceride. This conversion is very costlyalmost 25 percent of
the kilocalories must be spentand inefficient. The same is true for dietary protein.
Protein is first used for the numerous functions it provides to the body before excess is
converted to body fat. Even though the process is highly inefficient, excess kilocalories
in any form will be stored as a triglyceride through the process known as lipogenesis.
Lipogenesis is a separate anabolic pathway that synthesizes fatty acids to be stored
and is not just a reversal of the reactions involved in the breakdown of fat. In fact, the
two processes take place in different parts of the cell. Fatty acids are made in the cytosol rather than the mitochondria, where fats are oxidized. Lipogenesis also differs
from fat oxidation in the way its affected by glucagon and insulin. Glucagon stimulates lipolysis, which provides the fatty acids for beta-oxidation. Insulin has the opposite effect: It inhibits the breakdown of fat and promotes fatty acid synthesis.
Fatty acid synthesis begins with the two-carbon gateway molecule acetyl CoA.
This molecule eventually becomes a long-chain fatty acid that will attach to a glycerol
backbone and be stored as a triglyceride in fat cells.
s Andrew likely to store any of the kilocalories he eats during his
weekday afternoon snacking? Using the metabolic pathways,
explain how excess carbohydrates, proteins, and fats would
be stored.
24
The Take-Home Message Anabolic reactions are favored when you

ingest more kilocalories than you use to produce energy. Regardless of whether
the excess kilocalories are from carbohydrates, proteins, fats, or alcohol, the
excess energy can be converted to fat and stored. The metabolic pathways for
storing excess kilocalories are more efficient at storing dietary fat.
Table Tips
Important Advice
for Maintaining
Energy Levels
Eat breakfast! Its the most important
meal and will help improve energy levels
throughout the day.
What Happens if You Dont

Eat Enough?
Many Americans consume more than enough kilocalories to meet their energy demands, which is reflected in the current obesity crisis. But what happens when the opposite is true? That is, youre too busy with school and work to consume enough food,
or you choose not to eat? Regardless of the reason, when you do not consume enough
kilocalories to meet your energy needs, your body will turn to stored energy to produce energy.
While glycogen stores will supply energy during short periods of not eating, such
as overnight or between meals, the body will adapt differently if you go more than 18
hours without consuming carbohydrates. Initially, the body maintains blood glucose
levels by tapping into liver glycogen through glycogenolysis. At the same time, an increase in lipolysis provides fatty acids for energy, thus reducing the use of glucose by
the cell. In addition, gluconeogenesis is initiated using amino acids, glycerol, pyruvate,
and lactate to meet the bodys glucose needs once liver glycogen has been depleted. As
fasting continues, an alternative source of energy, ketone bodies, is derived from fatty
acids.
Dont skip meals; instead, be sure to eat

at least three meals and one to two small
snacks throughout the day.
Be sure each meal includes a combination
of protein, carbohydrates, and some fat.
Enjoy carbohydrate-rich foods such as
whole-grain crackers, baby carrots,
grapes, string cheese, and nuts as
snacks when you need a pick-me-up
between meals.
Drink plenty of fluid, especially water, so
youre sure to stay hydrated.
Ketogenesis Generates Energy

during Periods of Fasting
When deprived of carbohydrates, the body will depend less and less on glucose, and will
resort to using ketone bodies instead. Ketogenesis (the formation of ketone bodies illustrated in Figure 8.16 on the next page) reaches peak levels after an individual has
fasted or consumed a limited-carbohydrate diet for three days. By the fourth day of a
fast, the ketone bodies are providing almost half of the fuel used by the mitochondria.7
The presence of ketone bodies is referred to as ketosis, described in Chapter 5.
Ketone bodies form when there is an excess buildup of acetyl CoA. Acetyl CoA
accumulates because it is not being metabolized in the TCA cycle due to a reduced
supply of oxaloacetete (which comes from pyruvate and ultimately glucose). Thus,
metabolism depends on a supply of glucose to oxidize fatty acids to CO2 and water.
As you continue to fast, your brain will switch from glucose to ketone bodies for
fuel to reduce the drain on blood glucose. Eventually, about 30 percent of the brains
energy will come from ketone bodies, with the rest provided by blood glucose. The
differences in metabolism between feasting and fasting are listed in Table 8.3.
Ketogenesis is a normal metabolic response to fasting and is not life-threatening.
There can be consequences, however, when ketosis advances to ketoacidosis. This condition can occur in individuals with untreated type 1 diabetes mellitus because of the
ketogenesis The formation of ketone

bodies from excess acetyl CoA.
ketoacidosis A form of metabolic acidosis that occurs when excess ketone bodies are present in the blood; most often
seen in individuals with type I diabetes.
What Happens if You Dont Eat Enough?
25
Glycolysis
C C
CoA + H
H O
Acetyl CoA
Acetyl CoA
C C
CoA
H2O
H O
Acetyl CoA
TCA
Cycle
CoA CoA
H O H O
1
Electron
Transport Chain
C C C C
OH
H
H
Acetoacetate
H OH H O
H
C C C C
CO2
OH
2
H H H
Beta-hydroxybuterate
H O H
H
C C C
H
H
Acetone
Figure 8.16 The Formation of Ketone Bodies
(1) During ketogenesis, two molecules of acetyl CoA combine to form the ketone body
acetoacetate. (2) This ketone body can be metabolized to two other ketone bodies: acetone and
beta-hydroxybutyrate.
Table 8.3
Metabolism during Feasting and Fasting

Feasting: When You
Consume More Kilocalories
Than You Need
Fasting: When You Dont

Consume Enough Kilocalories
to Meet Your Energy Needs
Proteins
Amino acids are used for protein

synthesis or stored as a
triglyceride in the adipose tissue
Carbohydrates
Glucose is used for energy or

stored as glycogen in the liver
or muscle
Liver and muscle glycogen is broken

down to provide glucose for energy
Triglycerides
Fatty acids and glycerol are

stored as a triglyceride in the
adipose tissue
Triglycerides in adipose tissue are

broken down to glycerol and fatty acids
to be used for energy metabolism
If Fasting Continues After

Liver and Muscle Glycogen
Stores Are Depleted
Amino acids are used for gluconeogenesis or energy
Fatty acids are used to produce

ketone bodies and energy
lack of usable insulin, which lowers glucose availability to the cells. When ketone bodies accumulate, the blood pH drops. The body responds by increasing breathing to excrete more CO2, which increases the pH. If the level of ketone bodies surpasses the
kidneys ability to reabsorb them, they spill into the urine. Severe diabetic ketoacidosis can lead to impaired heart activity, coma, and even death.
26
n Tuesdays and Thursdays Andrew doesnt eat all day

because of his back-to-back laboratory classes. Using what
you have just learned, explain why Andrew experiences irritability
and fatigue at the end of the day. How can Andrew maintain
normal blood glucose levels when his carbohydrate intake is too
low? If he doesnt eat sufficient glucose, how does his metabolism
produce enough oxaloacetate for the TCA cycle to run efficiently?
During times of fasting or starvation, metabolism shifts to favor catabolic reactions. Fat is broken down to fatty acids
to be used for ATP synthesis, while glycerol and amino acids are used to maintain blood glucose levels. A lack of sufficient glucose in the blood can lead to
excess breakdown of fat and the synthesis of ketone bodies, which can be
used by the brain and muscles for energy.
How Does the Body

Metabolize Alcohol?
Despite the fact that alcohol (ethanol) contains kilocalories, it adds no nutritional
value to the diet and has no function in the human body, and is therefore not an essential nutrient. However, alcohol can be a significant source of energy. In fact, alcohol contains almost twice the amount of energy (7 kilocalories per gram) as an equal
amount of carbohydrate or protein (4 kilocalories per gram).
Alcohol is also different from carbohydrates, proteins, and fats because it doesnt
have to be digested before the body absorbs it. Rather, its absorbed directly through
the stomach mucosa and small intestine lining. This means that alcohol makes its way
into the blood soon after its ingested. Through the blood, alcohol is transported to
the liver, where it is metabolized.
The body can easily metabolize about half an ounce of alcohol, the amount in a
standard drink, in an hour and a half; however, when more than this amount is consumed in that period of time, the excess alcohol will circulate throughout the body
until the liver enzymes can break it down.
The Enzymes That

Metabolize Ethanol
Alcohol is metabolized through three distinct pathways. The primary pathway involves
the oxidation of ethanol by the enzyme alcohol dehydrogenase (ADH), which is found
in both the stomach and the liver. The liver contains enough ADH to metabolize alcohol efficiently. As you can see in Figure 8.17 on the next page, as soon as the capillaries deliver the alcohol to the liver cells, it is converted to acetaldehyde. This
dehydrogenase removes hydrogen ions from alcohol, which are picked up by coenzymes. More hydrogens are removed as acetaldehyde is quickly changed to acetate by
a similar enzyme called aldehyde dehydrogenase. The final step converts acetate to
acetyl CoA, which can be used to produce energy in the TCA cycle.
The second pathway that can oxidize alcohol is the microsomal ethanol oxidizing
system (MEOS). This system is not as significant as ADH but becomes more important
alcohol dehydrogenase (ADH) The

enzyme that converts alcohol to acetaldehyde; this is the first step in oxidizing
ethanol in the liver.
aldehyde dehydrogenase The enzyme that converts acetaldehyde to acetate;
this is the second step in oxidizing ethanol
in the liver.
microsomal ethanol oxidizing system (MEOS) The second metabolic
pathway for oxidizing ethanol, used at
higher intakes of alcohol; it also participates in metabolizing drugs.
How Does the Body Metabolize Alcohol?
27
Ethanol
Coenzyme
Coenzyme
1
H+
eAcetaldehyde
Pyruvate
Coenzyme
Triglycerides
Glycolysis
Coenzyme
H+
e-
1 In the liver, the alcohol

dehydrogenase converts
ethanol to acetaldehyde.
3
Acetyl CoA
Fatty acids
Acetyl CoA
CoA
Ketones
2 Acetaldehyde
dehydrogenase completes
the metabolism by forming
acetyl CoA.
TCA
TCA
Cycle
ATP
Electron
Transport Chain
3 The buildup of NADH from

drinking too much alcohol
results in the formation of
fatty acids and ketones.
Figure 8.17 The Metabolism of Alcohol

The liver is the main organ involved in the metabolism of alcohol.
with the consumption of larger amounts of alcohol. This system also metabolizes many
prescription and over-the-counter medications. If you drink alcohol with certain medications, the liver will metabolize the alcohol first, which causes the effects of the drugs
to be felt over a longer period of time. This is the reason drugs and alcohol should never
be taken together.
Not all alcohol is oxidized in the liver. There is a third metabolic pathway for alcohol that takes place in the brain, where alcohol is oxidized to acetaldehyde by the
enzyme catalase.8 This pathway may be responsible for some of the psychological effects people experience, such as reduced inhibitions, when they consume alcohol.
Excess Alcohol Is Stored as Fat

Fat metabolism shifts after you drink alcohol. When alcohol is consumed, fewer fatty
acids are used for energy. At the same time, the excess kilocalories in alcohol are metabolized and stored as fatty acids in the adipose tissue and liver. In chronic alcoholics,
excess fatty deposits in the liver can result in cirrhosis, the dangerous condition you
learned about in Chapter 7. Note that fat can begin to accumulate in the liver after a
single bout of heavy drinking.9
Alcohol is primarily absorbed and metabolized in the liver by two enzyme systems. The most efficient enzyme is ADH,
which converts the ethanol to acetaldehyde in the initial stages of metabolism.
The MEOS system, which is used when alcohol intake is high, also metabolizes drugs. A third system is found in the brain and metabolizes alcohol to acetaldehyde. Excess energy from alcohol cannot be stored and instead is
converted to fatty acids and stored as a triglyceride.
28
What Are Inborn Errors

of Metabolism?
Healthy individuals are born with all the necessary enzymes they need to control metabolism and function properly. However, some people carry a genetic condition in which
they lack an enzyme that controls a specific metabolic pathway. The result is a buildup of
abnormal by-products that can be toxic. Though such inborn errors of metabolism cannot be cured, they can be controlled through careful dietary treatment.Well discuss some
of the most common disorders involving protein and carbohydrate metabolism next.
Individuals with phenylketonuria (PKU) cannot convert the essential amino acid
phenylalanine to the nonessential amino acid tyrosine. Under these conditions, phenylalanine accumulates in the blood, a condition called hyperphenylalanemia. The treatment
for PKU is a controlled phenylalanine diet designed to maintain blood levels of phenylalanine and provide sufficient tyrosine, energy, and protein to grow and develop normally. Individuals with PKU must avoid high-protein foods and eliminate any products containing
aspartame (the sugar substitute found in NutraSweet), which contains phenylalanine.
Another protein-related disorder, maple syrup urine disease (MSUD), results
from an inability to metabolize the branched-chain amino acids leucine, isoleucine,
and valine. Babies with MSUD appear normal at birth but begin to show signs of the
disease, such as a maple syrup smell to their urine (hence the name), within a few
weeks. If left untreated, the condition can result in seizures, coma, and even death.10
The prescribed diet includes specially designed formulas and avoidance of foods such
as beef, chicken, fish, eggs, nuts, and legumes, which are high in the three affected
amino acids.11 Unfortunately, such a restrictive diet often means the child subsists
solely on specially designed formulas or medically created foods.
Homocystinuria occurs when the amino acids and homocysteine build up in the
blood, resulting in dislocation of the lens in the eye12, nearsightedness, and blood clots
in the veins and arteries.13 In adults, the high rate of blood clots and atherosclerosis,
especially in the carotid artery, could cause premature cardiovascular disease. A diet
low in methionine is prescribed as the treatment, along with a supplement of B vitamins including folate, vitamin B6, and vitamin B12.14
Two carbohydrate-related disorders are galactosemia and glycogen storage disease.
Galactosemia results in the inability to convert galactose to glucose. The treatment focuses mainly on restricting dietary lactose and galactose, which means avoiding products
that contain milk chocolate, whey protein or whey solids, casein, and dry milk solids, all
of which are made from milk products and may contain galactose.
Glycogen storage disease refers to the inability to break down glycogen and provide glucose for energy metabolism, or to maintain normal blood glucose levels between meals. To treat glycogen storage disease, foods that contain sucrose, lactose,
galactose, and fructose are restricted because these carbohydrates are often stored as
glycogen in the liver.
Table 8.4 on the next page summarizes these common genetic disorders and the
recommended dietary treatment for each.
Inborn errors of metabolism, such as

phenylketonuria, maple syrup urine disease, homocystinuria, galactosemia,
and glycogen storage disease are the result of a defective gene that affects
the metabolism of specific proteins or carbohydrates. The treatment for all genetic metabolic disorders includes a strict dietary regimen to control the symptoms while still providing adequate nutrients.
Special formulas and medically designed foods

have been developed to meet the nutritional
needs of children and adults with genetic
disorders such as maple syrup urine disease.
inborn errors of metabolism Genetic

conditions in which an individual lacks an
enzyme that controls a specific metabolic
pathway, resulting in the buildup of toxins.
phenylketonuria (PKU) A genetic
disorder characterized by the inability to
metabolize the essential amino acid
phenylalanine.
hyperphenylalanemia Elevated levels
of blood phenylalanine due to a lack of the
enzyme phenylalanine hydroxylase.
maple syrup urine disease (MSUD)
A genetic disorder characterized by the inability to metabolize branched-chain
amino acids; symptoms include a maple
syrup smell in the urine.
homocystinuria A genetic disorder
characterized by the inability to metabolize the essential amino acid methionine.
galactosemia The genetic disorder
characterized by high levels of galactose in
the blood due to the inability to convert
galactose to glucose.
glycogen storage disease A genetic
disorder characterized by the inability to
break down glycogen due to the lack of
glucose 6-phosphatase.
What Are Inborn Errors of Metabolism?
29
Table 8.4
Five Inborn Errors in Metabolism

Examples of
Acceptable Foods
Examples of Foods to Avoid
Phenylalanine hydroxylase
Fruits, vegetables, breads,

cereals, special formulas
Meat, chicken, fish, eggs, dairy,

nuts, legumes
1:300,000
Branched-chain alphaketo acid dehydrogenase
Foods low in branched-chain

amino acids, fruits, vegetables, breads, cereals,
specialized formulas
Meats, eggs, dairy, nuts, legumes
Homocystinuria
1:300,000
Cystathionine beta synthase
Fruits, vegetables, special

formulas
Meats, eggs, dairy
Galactosemia
1:65,000
Galactose 1-phosphate
uridyltransferase
Fruits, vegetables, breads,

cereals, eggs, meats
Milk, cheese, milk chocolate,

organ meats, legumes, hydrolyzed protein made from milk,
casein, fermented soy products
Glycogen storage
disease
1:50,000
Glucose 6-phosphatase
Corn starch and continuous

overnight feeds
Milk, cheese, fruits
Disorder
Incidence
Enzyme That Is Lacking
Phenylketonuria
1:15,000
Maple syrup
urine disease
CAREERS IN NUTRITION
Putting It All Together
Clinical Nutrition Specialist

Fran Rohr, MS, RD, LD
is the Clinical Nutrition
Specialist at the
Metabolism Department
of Childrens Hospital,
Boston. Read an interview with her
about her work with children with
inherited metabolic disorders online at
www.pearsonhighered.com/blake.
30
A healthful eating plan for an active person provides enough protein, carbohydrate,
fat, vitamins, minerals, and water to enable metabolism to work at an optimal level.
(Table 8.5 summarizes the metabolism of the energy nutrients found in food.)
If we consume more energy than we need, metabolism works to store the extra
kilocalories as glycogen or fat. Excess fat storage can lead to an increase in body weight
and increased risk of developing chronic disease.
If the guidelines for healthy eating are not met, an imbalance in nutrient intake
will cause a shift in metabolism to favor catabolic rather than anabolic reactions. While
this shift occurs throughout the day during normal eating, chronic fasting or starvation can result in ketosis and a breakdown of protein to meet blood glucose needs.
The Dietary Guidelines for Americans include recommendations for moderate alcohol intake. Ethanol in moderate amounts can be quickly metabolized in the liver to
acetyl CoA, which provides energy through the TCA cycle and the electron transport
chain. However, an excessive intake can redirect the acetyl CoA to fatty acids to be
stored as triglycerides in the liver and fat cells.
Balancing a nutrient-dense diet with irregular schedules can be challenging. However, the bodys metabolism is flexible enough to adapt to moderate changes in eating
and exercise patterns. The key is to provide adequate energy coupled with an optimal
intake of vitamins, minerals, and water. This approach will provide the fuel metabolism needs to meet daily energy requirements, sustain blood glucose levels, and maintain adequate fat stores without increasing the risk of chronic disease.
Table 8.5
Summary of Metabolic Processes in the Cells

Metabolic
Pathway
Nutrient(s) Involved
in the Pathway
Major Tissues
Involved
Type of
Pathway
Glycolysis
Carbohydrates
Metabolism of glucose to
produce pyruvate and two ATP
All cells
Catabolic and
anabolic
Glycogenesis
Carbohydrates
Producing glycogen from excess glucose
Muscle and liver
Anabolic
Glycogenolysis
Carbohydrates
Breakdown of glycogen to glucose
Muscle and liver
Catabolic
Gluconeogenesis
Noncarbohydrates,
including amino acids,
glycerol, pyruvate,
and lactate
Producing glucose from noncarbohydrate sources
Liver and kidneys
Anabolic
Beta-oxidation
Fatty acids
Fatty acid oxidation to acetyl CoA
Liver and muscle
Catabolic
Lipolysis
Fatty acids
Breakdown of triglycerides to yield fatty

acids and glycerol
Adipose and liver
Catabolic
Lipogenesis
Fatty acids
Synthesis of fatty acids and triglycerides
Adipose and liver
Anabolic
Ketogenesis
Fatty acids and

ketogenic
amino acids
The conversion of fatty acids and ketogenic amino acids to acetyl CoA and to
ketone bodies
Liver
Anabolic
Transamination
Amino acids
Formation of nonessential amino acids

produced by transferring an amine group
from one amino acid to an alpha-keto acid
Liver
Catabolic
TCA cycle
All nutrients
Oxidation of acetyl CoA to produce hydrogen ions, carbon dioxide, and GTP
All cells (except RBCs)
Catabolic and
anabolic
Electron transport
chain
All nutrients
Formation of ATP and water from hydrogen ions and protons generated during
glycolysis and the TCA cycle
All cells (except RBCs)
Catabolic (releases energy)
Description of the Pathway
Two Points of View

Can Genetics Be Used to Improve Nutritional Health?
Two experts in the field of nutritional genomics discuss
the interaction between genetic variations and nutrition.
Ruth DeBusk, PhD, RD
Jim Kaput, PhD
GENETICIST AND CLINICAL NUTRITIONIST
FOOD AND DRUG ADMINISTRATION (FDA)/NATIONAL

CENTER FOR TOXICOLOGICAL RESEARCH
Ruth DeBusk is a private practitioner

specializing in genetics, nutrition, and
gene-based counseling. She has authored numerous books, papers, and
Jim Kaput, PhD, is director of the

Division of Personalized Nutrition and
Medicine at the FDA. He previously held
continued
continued
Two Points of View
31
Can Genetics Be Used to Improve Nutritional Health? continued

Jim Kaput, PhD
articles, including the ADA publication Genetics: The Nutrition

Connection. She is also on the editorial board of the Journal
of the American Dietetic Association. Before entering private
practice, she was a faculty member at Florida State University,
where her research focused on how genes regulate the absorption of dietary nutrients.
concurrent positions at the University of Illinois Chicago, the

Bioinformatics Shared Resource Core of the NCMHD Center of
Excellence in Nutritional Genomics at the University of CaliforniaDavis, and as science advisor for International Alliances and
Best Practices for NuGO, the European Nutrigenomics Organization. He manages the UC Davis nutrigenomics list serve and is
the only contributor to its emails describing the science and applications of nutrigenomics for personal and public health. He is
also co-founder of the international Nutrigenomics Society (NxS)
and recently co-edited with Raymond Rodriguez Nutritional Genomics: Discovering the Path to Personalized Nutrition.
Q:
A:
What is nutritional genomics?

Nutritional genomics is a marriage between genetic technology and food and nutrition science. It helps us learn
how our genes and the diet and lifestyle choices we
make throughout our lives work together to determine
whether well be well or ill and, ultimately, how to maximize our genetic potential.
Q:
How will nutritional genomics potentially benefit

nutrition research and the consumer?
A:
The real promise of nutritional genomics is disease prevention. While we know that food and nutrition are keys
to health, its been difficult to get beyond general guidelines because everyone responds differently to the same
foods, diets, and lifestyle experiences. Even identical
twins, who have the same genetic material, can have
very different health outcomes. We now understand that
these differences are the result of the interaction between
our genes and our environment, which is the sum total
of the many food, dietary supplement, and lifestyle
choices we make throughout our lives. Nutritional genomics provides researchers with details of this interaction that were not previously known, such as how
particular genetic variations influence an individuals ability
to use nutrients and how bioactive dietary components in
food influence expression of the information in our genes.
Q:
What are the potential challenges of implementing

the research to everyday practice?
A:
I see two major challenges that I feel certain will resolve

as this field develops. The first is the need for a strong
foundation of nutritional genomics research. Unlike the
decades of basic and clinical research in pharmacology
that now form the foundation of pharmacogenomics, neither basic nor applied nutrition research has had the resources required to develop a similarly strong foundation
upon which to base nutritional genomics.
The second major challenge is the education and
training of the researchers who will conduct the basic
and clinical nutritional genomics research and for the clinicians who will translate the research findings into practical applications. Similarly, practitioners will be
challenged with a steep learning curve. With the exception of the nutrition professional, none of the health professional training programs includes more than a cursory
exploration of nutrition, genetics, or nutritional genomics.
32
Q:
A:
What is nutritional genomics?
Q:
How will nutritional genomics potentially benefit nutrition research and the consumer?
A:
A comprehensive nutritional genomics approach will yield

short- and long-term benefits to human health by (1) revealing novel nutrientgene interactions, (2) developing
new diagnostic tests for adverse responses to diets,
(3) identifying specific populations with special nutrient
needs, (4) improving the consistency of current definitions
and methodology related to dietary assessment, and
(5) providing the information for developing more nutritious plant and animal foods and food formulations that
promote health and prevent, mitigate, or cure disease.
Q:
What are the potential challenges of implementing

the research to everyday practice?
A:
While the potential benefits of personalized health care

are significant for individuals, public health, and the
Nutrigenomics seeks to provide a genetic understanding

for how common dietary chemicals (i.e., nutrition) affect human physiology at the molecular level and how individual
physiology affects the metabolism of nutrients. The conceptual basis for this new branch of genomic research can
best be summarized with the following five tenets:
Common dietary chemicals act on the human
genome, either directly or indirectly, to alter gene expression or structure.
Under certain circumstances and in some individuals, diet can be a serious risk factor for a number of
diseases.
Some diet-regulated genes (and their normal, common
variants) are likely to play a role in the onset, incidence,
progression, and/or severity of chronic diseases.
The degree to which diet influences the balance between healthy and disease states may depend on an
individuals genetic makeup.
Dietary intervention based on knowledge of nutritional
requirements, nutritional status, and genotype (i.e.,
individualized nutrition) can be used to prevent, mitigate, or cure chronic disease.
Can Genetics Be Used to Improve Nutritional Health? continued

Jim Kaput, PhD

economy, research and applications face a diversity of
challenges based on human genetic heterogeneity, the
complexity of foods, and the variable physiological
mechanisms that produce health or disease states. Another significant challenge is that association studies,
whether genetic, nutritional, or nutrigenomic, are based
on population studies that yield the attributable fraction
(AF)the proportional reduction in average disease
risk over a specified time interval that would be
achieved by eliminating the exposure of interest from
the populationwhile other factors remain unchanged.
For genetic association studies, the population attributable fraction is that proportion of cases in the population
that would be avoided if nobody carried the risk allele.
AF is often misinterpreted as a risk factor rather than the
fractional change in number of cases within the population. Perhaps most importantly, the attributable fraction
is usually calculated from population models and is not
directly applicable to individuals because individuals may
differ genetically, physiologically, and nutritionally from
the population averages.
There will be major capacity gaps in researchers,

clinicians, educators, counselors, and policymakers
that will need to be addressed at the undergraduate,
graduate, and postgraduate levels in order to provide the
variety of professionals needed for nutritional genomics.
Q:
A:
How do you address these potential challenges?

The technology exists for developing the research foundation for nutritional genomics. What is needed is significant funding and trained researchers and technical
personnel to design and execute the large studies that
are sufficiently powered to make strong associations between genetic variations and specific functional outcomes. From this foundation will come clinically relevant
approaches to disease management and disease prevention. Federal funding agencies are beginning to address the research funding needs and there is growing
international collaboration to pool information and resources in order to enhance the research output. All of
these activities should be encouraged.
The capacity gap is also beginning to be addressed.
Nutrition professionals are an obvious resource from
which to develop nutritional genomics researchers and
practitioners. However, nutrition professionals still face the
task of learning genetics and of integrating nutrition and
genetics into the science of nutritional genomics and its
practice applications. The American Dietetic Association
and university nutrition programs are playing a leadership
role in incorporating nutritional genomics into undergraduate and graduate education. Other associations and private concerns are developing training programs,
particularly for the postgraduate clinical nutritionist. Over
time, the education and training programs will be in place
and nutrition professionals will find it much easier to develop expertise in nutritional genomics.
Q:
A:
How do you address these potential challenges?

Omics technologies (i.e., genomics, proteomics,
metabolomics, and transcriptomics) provide the methodologies for analyzing health and disease processes. The
most important components for addressing these challenges will be the development of novel research strategies
that analyze individual responses. The next, intermediate
approach for experimental studies is the use of communitybased participatory research and primary care research,
where individuals are analyzed rather than populations.
An n = 1 research strategy is radically different than the
standard approach of determining average biological
responses. A second strategy focuses on analyzing the
healthy phenotypea process that might be done by
challenges to homeostasis. That is, perhaps long-term
health can be predicted by determining how an individual responds to a metabolic challenge. The prime example of such a challenge is the oral glucose tolerance test
for determining whether one has a normal glucose
response, impaired, or diabetic. Monitoring exercise
activity, immunological response to lipopolysaccharide
stimulation, or a dietary fat challenge are other examples.
Since there are many homeostatic systems, the full set of
these challenges has not yet been determined.
Two Points of View
33
The Top Ten Points

to Remember
1. Metabolism is the sum of all chemical reactions in the
2.
3.
4.
5.
6.
34
body. Metabolism balances anabolic reactions that create large molecules from smaller parts with catabolic
reactions that break apart large molecules to produce
energy and create building blocks for essential compounds. These reactions are turned on and off by hormones and are stimulated by enzymes, coenzymes, and
cofactors.
Glucose, the main monosaccharide in metabolism, is
oxidized through glycolysis to form pyruvate. If there
is sufficient oxygen in the cell, pyruvate continues
down the pathway to acetyl CoA and enters the TCA
cycle. If there is not sufficient oxygen, pyruvate is converted to lactate.
Once amino acids have been deaminated, the remaining carbon skeletons can be oxidized for energy in the
TCA cycle. The carbon skeletons of glucogenic amino
acids can be transformed into pyruvate and participate
in gluconeogenesis, while ketogenic amino acids are
converted to acetyl CoA and are either oxidized in the
TCA cycle or transformed into fatty acids and stored
as triglycerides.
Triglycerides are hydrolyzed to glycerol and fatty acids
before they are metabolized. Glycerol enters the metabolic pathway during anaerobic glycolysis, while fatty
acids undergo beta-oxidation to form acetyl CoA.
Fatty acids cannot be used for gluconeogenesis because the reaction from pyruvate to acetyl CoA is
irreversible.
The TCA cycle begins with acetyl CoA, which is
formed from the metabolism of carbohydrates, proteins, and fats. The products of the TCA cycle include
coenzymes, which transfer hydrogen atoms and electrons to the electron transport chain.
The electron transport chain produces the majority of
required ATP by transferring the hydrogen atoms and
electrons generated during glycolysis and the TCA
cycle through a series of chemical reactions that produce ATP and water. The electron transport chain
takes place within the mitochondria.
7. Excess kilocalories, regardless of whether they are from
8.
9.
10.
carbohydrates, proteins, fats, or alcohol, stimulate fat

synthesis and are stored as triglycerides. Excess carbohydrates and amino acids can also be stored as glycogen.
Fasting or starvation shifts the metabolism from anabolic reactions to catabolic reactions to maintain energy balance. The body uses stored glycogen and fatty
acids from stored triglycerides in the early stages of
fasting. As fasting continues, the body increases the
breakdown of fats for energy and conversion to ketone
bodies, which can be used by the brain and muscle.
Blood glucose levels are maintained using amino
acids, pyruvate, lactate, and glycerol as precursors in
gluconeogenesis.
Alcohol is metabolized in the liver to acetyl CoA by the
enzyme system ADH. The acetyl CoA enters the TCA
cycle to produce energy. When an excess of alcohol
builds up, the acetyl CoA is converted to fatty acids
and stored as a triglyceride in the liver. The consumption of excess alcohol can result in the buildup of
stored fat in the liver, leading to a condition called
cirrhosis.
Inborn errors of metabolism are genetic disorders that
can disrupt one or more metabolic pathways, due to
the lack of an enzyme involved in either protein or
carbohydrate metabolism.
Test Your Knowledge

1. Glycolysis is a metabolic pathway that breaks down glucose for energy. This is an example of a(n)
a. anabolic reaction.
b. catabolic reaction.
2. The energy molecule that fuels metabolism is
a. adenosine diphosphate.
b. adenosine triphosphate.
c. creatine phosphate.
d. acetyl CoA.
3. The first stage in using carbohydrates for energy metabolism is called
a. beta-oxidation.
b. the Cori cycle.
c. glycolysis.
d. the electron transport chain.
4. When your diet contains excess glucose and youve met

your energy needs, these energy-rich nutrients can be
stored as a triglyceride after first being converted to
a. protein.
b. fatty acids.
c. citrate.
d. oxaloacetate.
5. The compounds that can used for gluconeogenesis include
a. pyruvate.
b. lactate.
c. glucogenic amino acids.
d. glycerol.
e. all of the above.
6. Ketogenic amino acids that become acetyl CoA
a. are used in gluconeogenesis to produce glucose.
b. are used in ketogenesis to form ketone bodies.
c. are used in transamination to form nonessential amino
acids.
d. are used in glycolysis to provide ATP.
7. If you dont eat enough food, especially carbohydrates, to
meet your bodys energy needs,
a. ketogenesis is stimulated.
b. gluconeogenesis is stimulated.
c. fatty acid oxidation is stimulated.
d. all of the above may occur.
8. If your diet contains excess protein, the excess amino acids
are
a. deaminated and then converted to ATP or fatty acids.
b. stored as glycogen in the liver.
c. stored as protein in the muscle.
d. all of the above happen.
9. Fatty acids cannot be used for gluconeogenesis because
a. they lack sufficient carbons to form glucose.
b. they are converted to acetyl CoA, which cant reform
pyruvate.
c. they are converted to oxaloacetate, which cant reform
pyruvate.
d. they enter the TCA cycle through citrate.
10. Your metabolism is regulated by
a. hormones such as insulin and glucagon.
b. enzyme activity.
c. the amount of ATP in your cells.
d. all of the above.
Answers
1. (c) Catabolic reactions are those that break apart larger
molecules into smaller molecules. Anabolic reactions are
the opposite and build larger molecules from smaller
molecules.
2. (b) Adenosine triphosphate (ATP) is a high-energy molecule that, when hydrolyzed to adenosine disphosphate
(ADP), provides energy to cells. ATP can be reformed by
adding an inorganic phosphate to ADP donated from the
initial reaction, or from creatine phosphate (PCr).
3. (c) Glycolysis is the first stage of carbohydrate metabolism. Eventually, the hydrogen atoms and electrons generated from glycolysis are carried to the electron transport
chain. Beta-oxidation is the metabolic pathway used to
convert fatty acids to acetyl CoA. At the end of glycolysis,
pyruvate can be converted to lactate, which is converted
into glucose through the Cori cycle in the liver.
4. (b) Excess glucose can be converted to fatty acids and
stored as a triglyceride when glycogen stores have reached
their maximum capacity. Citrate and oxaloacetate are intermediate compounds in the TCA cycle. Although some
carbon skeletons from glucose metabolism can be converted to nonessential amino acids, this is not a storage
form for excess glucose.
5. (e) Pyruvate, glucogenic amino acids (such as alanine),
glycerol, and lactate can all be transformed into glucose
through gluconeogenesis.
6. (b) Ketogenic amino acids can be used to form ketone
bodies by first being converted to acetyl CoA.
7. (d) If an individual does not eat sufficient kilocalories,
the body will use other metabolic pathways, including
fatty acid oxidation and gluconeogenesis, to provide energy and maintain blood glucose levels. If fasting or starvation continues, ketogenesis increases due to the rapid
breakdown of stored fat. Ketone bodies can be used by
the brain and muscles for energy.
8. (a) Because we cant store excess amino acids as protein,
we have to either use them for ATP synthesis or convert
them to fatty acids and store them as a triglyceride.
9. (b) Fatty acids contain sufficient carbons but they are
converted to acetyl CoA, which is not able to form the
pyruvate needed for gluconeogenesis.
10. (d) Metabolism is controlled by hormones, which are
released in response to changes in ATP and enzyme
activity.
Test Your Knowledge
35
Answers to Myths
and Misperceptions
1. True. All chemical reactions involved in metabolism take
place within the mitochondria or the cytosol of cells.
2. True. The body metabolizes carbohydrates mostly as glucose through glycolysis, which produces more energy in
the form of ATP than it uses compared with amino acid
and fatty acid metabolism.
3. False. Most fructose is converted to glucose before entering the metabolic pathway.
4. False. A burning sensation in muscles during strenuous
exercise is caused by the reduction in pH due to the
buildup of hydrogen ions, not the buildup of lactate.
5. False. Once protein and energy needs have been met, excess amino acids are converted to fatty acids through acetyl
CoA and stored as triglycerides in fat cells. Thus excess intake of dietary protein will not result in larger muscle.
6. False. Fatty acids are oxidized in the TCA cycle when cells
contain sufficient oxygen. Under the anaerobic conditions
of high-intensity exercise, a larger percentage of glucose,
rather than fatty acids, is used for energy production.
36
7. False. During alcohol metabolism in the liver, ethanol is

converted to acetyl CoA, which either enters the TCA
cycle or is transformed into fatty acids. Acetyl CoA cannot be used to produce glucose.
8. False. Vitamins and minerals in foods do not provide energy. However, the B vitamins niacin and riboflavin are
essential for energy production because of their roles as
coenzymes during metabolism. As coenzymes, they accept hydrogen atoms and electrons produced during glycolysis and the TCA cycle, which are in turn used by the
electron transport chain to produce energy.
9. False. Regardless of what time of day you eat, an excess
of total kilocalories favors anabolic metabolism, which
means you store the excess kilocalories as body fat or
glycogen. If you consume fewer kilocalories than you
need each day for metabolism, catabolic reactions are favored, resulting in a breakdown of triglycerides.
10. False. Inborn errors of metabolism are the result of a genetic mutation that causes a specific metabolic enzyme to
be either missing or produced in inadequate amounts.
The gene is not repaired during puberty, and the disorders cannot be outgrown.
Web Support
For general information on genetic disorders, visit the National Human Genome Research Institute at www.nhgri
.nih.gov
For more information on phenylketonuria, visit the California Coalition for PKU and Allied Disorders at www
.pkuparents.org
For more information on galactosemia, visit Parents of
Galactosemia Children, Inc. at www.galactosemia.org
For more information from a peer-reviewed online
journal, visit Nutrition and Metabolism at www
.nutritionandmetabolism.com.
References
1. Stipanuk, M. H. 2000. Biochemical and Physiological Aspects of Human
Nutrition. Philadelphia: W. B. Saunders.
2. Schrder, H., N. Terrados, and A. Tramullas. 2005. Risk Assessment of the
Potential Side Effects of Long-term Creatine Supplementation in Team
Sport Athletes. European Journal of Nutrition 44:255261.
3. Tortora, G., B. Funke, and C. Case. 2007. Microbiology: An Introduction.

San Francisco: Pearson Benjamin Cummings.
4. Berg, J. M., J. L. Tymoczko, and L. Stryer. 2001. Biochemistry. 5th ed. New
York: W. H. Freeman and Company.
5. Ibid.
6. Ibid.
7. Shils, M. E., M. Shike, A. C. Ross, B. Caballero, R. J. Cousins. 2006.
Modern Nutrition in Health and Disease. 10th ed. Philadelphia:
Lippincott Williams & Williams.
8. Zimatkin, S. M., and A. L. Buben. 2007. Ethanol Oxidation in the Living
Brain. Alcohol and Alcoholism 42:529532.
9. Berg, Biochemistry.
10. Mitsubuchi, H., M. Owada, and F. Endo. 2005. Markers Associated with
Inborn Errors of Metabolism of Branched-chain Amino Acids and Their
Relevance to Upper Levels of Intake in Healthy People: An Implication
from Clinical and Molecular Investigations on Maple Syrup Urine Disease. Journal of Nutrition 135:1565S1570S.
11. Shils, Modern Nutrition in Health and Disease.
12. Burton, M. J., K. J. Burton, and C. M. Chuka-Okosa. 2002. Plummeting
Lenses in the TB Clinic. The Lancet 360:138.
13. Thambyrajah, J. and J. N. Townend. 2000. Homocysteine and
AtherothrombosisMechanisms for Injury. European Heart Journal
21:967974.
14. Robinson, K., E. Mayer, and D. W. Jacobsen. 1994. Homocysteine and
Coronary Artery Disease. Cleveland Clinic Journal of Medicine
61:438450.
References
37

Your Body's Metabolism Explained

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8

2. The body prefers to use carbohydrates for fuel because

3. Fructose is preferable to glucose as an energy

Lactate buildup during exercise causes a burning

sensation in the legs. T/F

protein is stored in the

muscle and therefore increases muscle size. T/F

6. Fat is the main fuel used during high-intensity

7. Alcohol is converted to blood sugar

B vitamins provide energy. T/F

9. Kilocalories consumed after 7:00 p.m. are automatically

stored as fat and contribute to weight gain.

will outgrow such disorders when they reach puberty. T/F

10. Describe the causes, diagnosis,

Clearly, Andrews energy needs vary

Chapter 8 . Your Bodys Metabolism

Metabolism Takes Place Within Cells

The Liver Plays a Central Role

Figure 8.1 Overview of Energy

metabolism The sum of all chemical

Mitochondria play a key

Figure 8.2 Metabolism Takes Place Within Cells

mitochondrion A cellular organelle that

Figure 8.3 The Metabolic Fate of Food

Metabolism Follows Individual

Anabolic and Catabolic Reactions

anabolic reactions Metabolic reactions

Chapter 8 . Your Bodys Metabolism

a Anabolic reactions use ATP

Figure 8.4 Anabolic and Catabolic

b Catabolic reactions break

Enzymes and Hormones

catabolic reactions Metabolic reactions that break large compounds into

The Major Hormones That Control Metabolism

Stimulates protein synthesis

Increases glycogen synthesis

Stimulates protein degradation

Stimulates protein degradation

Can Energy Drinks Alter Your Metabolism?

Energy Drinks Contain

sound like an easy recipe for weight

Side Effects of Caffeine

awake during an all-night study session,

Energy Drinks and Alcohol

Caffeine Content of Energy Drinks and Common Beverages

SoBe Adrenaline Rush

Taurine, carnitine, inositol, ginseng, vitamins

Vitamins, corn syrup

Taurine, guarana, panax, ginseng, maltodextrin

Taurine, inositol, vitamins

Red Bull Sugarfree

Taurine, inositol, aspartame, vitamins

Taurine, guarana, ginseng, Ginkgo biloba, vitamins

Yerba mat, ginseng, choline, guarana, vitamins

High-fructose corn syrup

High-fructose corn syrup

Mountain Dew DMX

Ginseng, taurine, guarana, maltodextrin

Starbucks brewed coffee

Chapter 8 . Your Bodys Metabolism

ways: ethanol acts as a depressant, while

Blending alcohol with caffeine can also