Download LESSON 2.2 WORKBOOK Metabolism: Glucose is the

LESSON 2.2 WORKBOOK
Metabolism: Glucose is the
middleman for ATP
DEFINITIONS OF TERMS
Homeostasis — The tendency toward a relatively stable
equilibrium that is maintained by
physiological processes.
In Lesson 2.1 we discussed the digestion and
absorption of nutrients. After the nutrients are absorbed, what are they used for? In this lesson we
will discuss the process by which energy is made
from the macronutrients. We will identify the steps
in glucose metabolism that are important in the
production of ATP, and explore why it is so important to maintain blood glucose homeostasis.
Glucose
For a complete list of defined
terms, see the Glossary.
Metabolism makes the macronutrients useful
In Lesson 2.1 we learned that the monomer forms of the macronutrients are the forms that can be
absorbed in the small intestine. Once the macronutrients reach the liver, metabolism takes those monomers and breaks them down into even simpler forms that have two main functions: they can become
building blocks for cellular structures or they can be used to make the ATP that cells use for energy.
Macronutrients are metabolized in the liver
Wo r k b o o k
Lesson 2.2
After being absorbed in the small intestines, carbohydrates, lipids and proteins travel in the blood to the
liver. Over the next series of lessons you will see that the liver is the master regulator of metabolism. The
liver is often referred to as the biochemist of the body because it can perform chemical reactions that
other tissues cannot. For example, the liver stores glucose as glycogen, repackages fatty acids for storage
and makes new amino acids. The liver is also the primary organ for making new glucose, which is a very
important job. In fact, the liver is the only organ that can make macronutrients from other macronutrients.
Because of this, the liver plays a central role in maintaining a constant concentration of glucose in the
blood stream. This is important because the brain and the red blood cells can only use glucose for energy!
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
72
LESSON READINGS
The energy in macronutrients is shuffled through many forms to generate ATP
The release of energy from macronutrients involves breaking chemical bonds because that is where the
energy is stored. Different types of bonds contain different amounts of energy, remember it is the combustible energy in the macronutrients that is used to derive calories. As bonds in the macronutrients are
broken the energy is released and recaptured into a new chemical bond that is the universal fuel source
of all cells, ATP. So, the end goal of metabolism is to put the energy from the bonds of the macronutrients
into the energy in the bonds of ATP.
DEFINITIONS OF TERMS
ATP — The molecular unit of
energy used by all cells in the
body.
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 2.2
ATP is the energy source for our cells
For the energy in macronutrients to be used in cellular activities the combustible energy in the carboncarbon bonds is transferred to a compound called adenosine triphosphate (ATP). ATP and its related
compounds ADP (adenosine diphosphate) and AMP (adenosine monophosphate) are the key energyproducing molecules used by cells. As shown
in Figure 1, one molecule of ATP consists of
High Energy
the nucleoside adenosine and three phosphate
Phosphate
Bonds!
groups. The phosphate groups are negatively
charged and don’t like being close to one another,
therefore the bond connecting the phosphates
has a lot of energy. You can think of this like
Phosphate Groups!
magnets: if you have two strong magnets and
Adenosine!
hold them close to each other they’ll either snap
together or repel one another. Now imagine the
strength it takes to force the magnets together
while they are repelling each other – this is what
the bonds holding the phosphate groups together
is doing. These bonds are extremely high energy,
and when they break energy is released. Cells
use the high energy in the phosphate bonds to
Figure 1: The molecular structure of ATP:
catalyze vast numbers of enzymatic reactions
the energy of ATP is stored in the bonds
required for life. For example, energy from ATP is
connecting the phosphate groups. When
required to make new amino acids in the liver.
those bonds are broken, energy is released.
1. The type of energy stored in
chemical bonds is:
aa. Thermal energy.
bb. Electrical energy.
cc. Potential energy.
dd. Combustible energy.
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
73
LESSON READINGS
From glucose to ATP
DEFINITIONS OF TERMS
Acetyl CoA — A molecule that
shuttles carbons to the citric acid
cycle.
Citric acid cycle — A cycle of
reactions used to generate energy
that takes place in the mitochondria.
Any cell that has mitochondria can
do this.
Electron transport chain — A
chain of proteins that transfers
protons from hydrogen across a
membrane, keeping them separate
from electrons. The energy released
at the end of the chain is used to
generate ATP.
Glycolysis — The breakdown of
glucose to produce energy.
NADH — A molecule that shuttles
hydrogens into the electron transport
chain.
Pyruvate — A molecule created
from glucose and some amino acids.
For a complete list of defined terms,
see the Glossary.
Wo r k b o o k
Lesson 2.2
How does the energy from ATP relate to the calories in a food? When the macronutrients we eat are
digested down to sugars, amino acids and fatty acids they can then be used to produce ATP, which is
maintained in all cells until needed. The homeostasis of blood glucose is important because ATP can’t
travel in the blood, so glucose is the middleman passed between cells and used to synthesize ATP. Every
cell in the body conducts glycolysis, a process used to convert glucose to acetyl CoA, and almost every
cell can then use the acetyl CoA in the citric acid cycle and the electron transport chain to make more
ATP. Additionally, only particular organs can use fatty acids or amino acids to produce ATP, while all cell
types use glucose. Don't be alarmed by all the new terms here, we will be seeing them again!
Mitochondria are the energy factories of the cell
You may remember that mitochondria are organelles located within cells. What is important about the
mitochondrion is that it has two membranes: an inner membrane and an outer membrane. Because of
this, the mitochondria can keep steps
in metabolism separated. We will see
Inner Membrane!
Inner Membrane!
how separating molecules is important
more when we discuss the electron
transport chain. The mitochondrion is
the location for the citric acid cycle, the
electron transport chain and breakdown
Outer Membrane!
Outer Membrane!
of fatty acids for energy, meaning that
every cell that has mitochondria can
participate in those reactions. Red
Figure 2: By having both an outer and an inner
membrane, the mitochondria can keep certain
blood cells do not contain mitochondria,
molecules and reactions separate.
and therefore can only use glycolysis
for energy.
Glycolysis: Converting glucose to acetyl CoA
The first steps of glucose metabolism occur in the cytosol of cells, and are called glycolysis (glycolysis
means ‘breaking down glucose’). As you can see on the next page in Figure 3, the six carbons (shown
in blue) of glucose are converted into two pyruvate molecules, each containing three carbons. Because
energy is stored in the carbon bonds, breaking the glucose into two pieces releases energy, resulting in
the production of two molecules of ATP. Glycolysis also produces a molecule called NADH, an energy
intermediate used to make ATP in the electron transport chain.
2. ATP is:
aa. Generated in the mitochondria.
bb. Used by all cells except the brain
and red blood cells.
cc. Absorbed from the foods that we
eat.
dd. Easily transported in the blood.
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
74
LESSON READINGS
The two pyruvates are shuttled into the
mitochondria where one more carbon
is removed, resulting in acetyl CoA and
another NADH. As we will see in this unit,
acetyl CoA is an important molecule that is
at the crossroads of glucose metabolism,
fatty acid metabolism and amino acid
metabolism.
Glucose!
Glycolysis!
Pyruvate!
Acetyl CoA!
What does breathing have to do with
metabolism?
Carbon!
Citric Acid Cycle!
As carbons are removed in metabolism, they
Energy Released!
exit the cell as carbon dioxide (CO2), and we
eventually breathe it out. If we were to hold
Figure 3: In glycolysis glucose is converted
into acetyl CoA, which is transported into the
our breath for too long, the CO2 would build
mitochondria where it goes into the citric acid
up in our blood and become toxic. Additioncycle.
ally, breathing brings in fresh oxygen that is
needed for metabolism to occur. The citric
acid cycle and the electron transport chain are both aerobic processes, meaning that they require oxygen.
In times when we are not breathing quickly enough, like in exercise, the citric acid cycle cannot occur. Our
brain is the organ that is the most sensitive to oxygen deprivation, and even a short time without breathing
in oxygen can have detrimental effects to our nervous system.
Acetyl CoA is shuttled into the citric acid cycle in the mitochondria
Wo r k b o o k
Lesson 2.2
Figure 4: NADH and FADH2
work like delivery trucks, shuttling hydrogen from water to
the electron transport chain.
The major way energy released by glucose metabolism
intersects with the electron transport chain is via the citric acid
cycle, which takes place in the mitochondria. When acetyl CoA
enters the mitochondria and participates in the citric acid cycle, it
first joins with four other carbons (see Figure 3 above). Subsequently, the carbon bonds are broken down releasing energy.
That energy is used to transfer a hydrogen ion from water to
NAD+, forming NADH, as shown in Figure 5. Similarly, two
hydrogen ions can be added to FAD to make FADH2. NADH and
FADH2 work like delivery trucks, taking hydrogen from water and
delivering to the next step in metabolism: The electron transport
chain.
3. Acetyl CoA is:
aa. Made out of carbons and a
B-vitamin.
bb. The molecule that connects
glucose, amino acid, and fatty
acid metabolism.
cc. The form in which energy is
stored in cells.
dd. Both A and B.
ee. All of the above.
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
75
LESSON READINGS
At the end of one turn of the
citric acid cycle, 3 NADH, 1
FADH2 and only 1 ATP are
produced. The NADH and
FADH2 are then used in the
electron transport chain to
produce 9 additional ATP.
The electron transport chain
is critically important because
it provides 90% of the ATP
obtained from the metabolism
of glucose.
1)  Carbons bonded together"
2)  A bond is broken, releasing energy"
3)  That energy is used to remove a
hydrogen from water and place it on
NAD NAD+"
Figure 5: Energy is transferred from the bonds holding
carbons together to the bond attaching hydrogen to NAD+.
Final steps: The electron
transport chain
Outer Membrane!
H
+ H
+ H
+ H
+ Inner Membrane!
-­‐ -­‐ -­‐ -­‐ ADP
!
ATP!
Figure 6: The positive protons of hydrogen (H+) and
the negative electrons (-) are kept separate in the electron transport chain until the end, where the protons
go down their energy gradient to make ATP, using the
enzyme ATP synthase.
Wo r k b o o k
Lesson 2.2
Each hydrogen that is added to
NAD+ and FAD contains one proton
and one electron. The positively
charged proton, and the negatively
charge electron are highly attracted
to one another, and prefer to be
kept close. In the electron transport
chain the protons and electrons from
the hydrogen are split apart and
kept separate by the membranes of
the mitochondria, as shown in the
figure to the left. Once separated the
attraction of the proton and electron
create a 'pressure'.
We can again use the idea of magnets to think of the energy in the electron transport chain. The negative
electrons and positive protons are like strong magnets that are attracted to one another. A great amount of
effort is required to separate the two, and when you bring them near one another they snap back together.
The inner mitochondrial membrane is what is used to keep the protons and electrons separated until the
last step of the electron transport chain, where the protons are allowed to travel through a channel in an
enzyme called ATP synthase.
4. Which of the following is NOT true
about the citric acid cycle?
aa. It takes place in the
mitochondria.
bb. It requires oxygen.
cc. It creates NADH and FADH2.
dd. All cells can do it.
5. Which of the following would prevent
the electron transport chain from
functioning?
aa. If ATP levels were too low.
bb. If no glucose was available to the
liver.
cc. If the protons were not kept
seperate from the electrons.
dd. If too much NADH is produced.
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
76
LESSON READINGS
DEFINITIONS OF TERMS
Brown adipose tissue — A type
of adipose tissue that is abundant
in newborns and hibernating
mammals. It generates body heat
in animals that do not shiver.
For a complete list of defined
terms, see the Glossary.
ATP synthase is an enzyme that
can harness the energy released
as the protons and electrons are
allowed to rejoin, and uses that
energy to add a phosphate group
onto ADP, creating new ATP. You
can think of ATP synthase as a
water turbine: the protons trapped
in the inter-membrane space are
Figure 7: Protons move though ATP synthase and drive
like water trapped in a dammed
the production of ATP like a turbine collects energy from
off lake. Once the dam is opened,
water flowing through a hydroelectric power plant.
the water flows out of the lake and
moves a water turbine. This movement of the water turbine generates electricity for us to use. Similarly, as the protons are allowed to flow
through the ATP synthase channel the energy actually rotates a part of ATP synthase, generating energy
to make new ATP.
Brown fat tissue uses the electron transport chain to keep us warm!
If the energy that is released as the protons flow back to their
electrons is enough to maintain the energy needs of our cells,
what would happen if the energy was not redirected into ATP?
There is a type of fat tissue called brown adipose tissue that is
highly concentrated with mitochondria. In these mitochondria a
separate channel exists other than ATP synthase that lets protons
rejoin the electrons. Instead of producing ATP, this channel lets
the energy be released as heat, raising body temperature. Babies
have higher concentrations of brown adipose tissue than adults,
and are used to keep the infants warm. Additionally, people living
in colder climates may have more brown adipose tissue than
people in warm climates.
Figure 8: People living in
cold climates have extra brown
fat to keep the body warm.
How the liver keeps blood glucose levels constant
Wo r k b o o k
Lesson 2.2
ATP cannot be transported in the blood, so each cell in your body must produce its own ATP. To do this, a
constant supply of glucose must be available in the blood, especially for the brain and the red blood cells
that can only use glucose for energy! The liver can supply new glucose to the blood, and the muscles and
adipose tissue can provide amino acids and fatty acids.
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
77
LESSON READINGS
6. Glucose is the only type of nutrient
used to release energy:
aa. True.
bb. False.
Acetyl CoA shuttles carbons between cycles
If glucose levels were low and no glucose became available in the blood
your brain would shut down! The body must call upon other nutrients – fats
and proteins, to supply the glucose or glucose-like compounds it needs.
Conversely, in times of plenty the body stores away excess nutrients as fat
and as protein to call upon later. At the crossroads of this whole process is
acetyl CoA. Glucose, fatty acids and amino acids all interact with acetyl CoA,
the consequences of which will depend on the energy requirements of the
cell at that time. Acetyl CoA can either direct metabolites into energy producing, or energy storing, pathways.
Releasing energy from fat
Wo r k b o o k
Lesson 2.2
Figure 9: Acetyl
CoA is the crossroads between
glucose, fatty acids
and amino acids.
Just as cells release energy from carbohydrates and trap it as ATP, they also release and trap energy from
triglycerides. Recall that triglycerides are molecules formed by the combination of fatty acids and glycerol.
During periods of low calorie intake or fasting the triglycerides are broken down into fatty acids and
glycerol. Carbons are cut off of fatty acids, two at a time, and can be made into acetyl CoA. Acetyl CoA
then enters the citric acid cycle to produce NADH and FADH2 to be used in the electron transport chain as
discussed above. Because fatty
acids have a lot more carbons
Fatty Acid (Palmitate)!
than a molecule of glucose, they
can be used to make more ATP
than glucose can. Additionally,
the process of breaking off the
x 8!
Acetyl CoA!
2-carbon fragments from fatty
acids releases one NADH and
one FADH2 molecule, so for every
2-carbon fragment that is shuttled
Carbon!
Citric Acid Cycle!
through the citric acid cycle, the
Amino Group!
total yield is 14 ATP. Palmitate
Energy Released!
is a common fatty acid found in
palm oil, and contains 16 carbons
(Figure 10). Therefore, metaboAmino Acid!
lism of palmitate would yield 108
molecules of ATP!
Figure 10: Fatty acids provide acetyl CoA for the citric
acid cycle, but completing the cycle also required amino
acids.
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
78
LESSON READINGS
Releasing energy from amino acids
Protein is the other energy-containing
macronutrient, however it is rarely used
to produce energy. Amino acids are
usually used to produce the proteins
the body needs. In starvation when
glycogen stores are depleted, some
amino acids can be used to make
energy by breaking apart their carbon
bonds to make pyruvate, acetyl CoA,
or other intermediates in the citric acid
cycle, depending on the shape of the
amino acid. Figure 11 shows some
amino acids being used in the citric
acid cycle.
Carbon!
Amino Group!
Energy Released!
Citric Acid Cycle!
Amino Acid!
Figure 11: Amino acids can enter the citric acid cycle
once their amino groups are removed.
How are the micronutrients
involved?
Vitamins and minerals have numerous functions in the human body, ranging from bone structure to
immune function. They also play an important role in metabolism. Vitamins and minerals are required for
many metabolic pathways. For example, the B-vitamins (thiamin, riboflavin, niacin, pantothenic acid, biotin,
vitamin B6, folate, and vitamin B-12) as well as iron and copper are required for acetyl CoA to function.
Some of the key players in metabolism that we discussed today are made from the B-vitamins: the CoA
part of acetyl CoA is synthesized from pantothenic acid, NADH is made from fiacin, and FADH2 is made
from riboflavin. People that have a deficiency in one or more of these vitamins cannot readily make ATP,
and can become fatigued and have neurological disorders.
Wo r k b o o k
Lesson 2.2
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
________________________________
79
STUDENT RESPONSES
Dinitrophenol (DNP) is a chemical that was sold as a diet pill in the first half of the 1900’s. DNP prevents the mitochondria from
being able to separate protons and electrons. Why would this cause someone to lose weight? Can you guess why this drug is
no longer allowed?
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
Remember to identify your
sources
____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
_____________________________________________________________________________________________________
Wo r k b o o k
Lesson 2.2
_____________________________________________________________________________________________________
___________________________________________________________________________________________
80
TERMS
TERM
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 2.2
DEFINITION
Acetyl CoA
A molecule that shuttles carbons to the citric acid cycle.
Brown Adipose Tissue
A type of adipose tissue that is abundant in newborns and hibernating mammals. It generates body heat in
animals that do not shiver.
Citric Acid Cycle
A cycle of reactions used to generate energy that takes place in the mitochondria. Any cell that has mito­
chondria can do this.
Electron Transport Chain
A chain of proteins that transfers protons from hydrogen across a membrane, keeping them separate from
electrons. The energy released at the end of the chain is used to generate ATP.
Glycolysis
The breakdown of glucose to produce energy.
Homeostasis
The tendency toward a relatively stable equilibrium that is maintained by physiological processes.
NADH
A molecule that shuttles hydrogens into the electron transport chain.
Pyruvate
A molecule created from glucose and some amino acids.
81