Download Glucose homeostasis in the blood (2) – un-storing energy

LESSON 2.4 WORKBOOK
Part two: Glucose homeostasis in
the blood – Un-Storing energy
DEFINITIONS OF TERMS
Fasting — A state of abstinence
from all food or drinks that provide calories.
For a complete list of defined
terms, see the Glossary.
In the previous lesson we learned about the
metabolic pathways the liver uses to shuttle
energy from glucose into storage as glycogen,
fat, and amino acids. In this lesson, we will focus
on the reverse: metabolism of glycogen, fats and
amino acids to generate glucose. We will also
discuss the different stages your body undergoes
during fasting.
Low blood sugar: Causes and consequences
Why is low blood glucose a problem?
Wo r k b o o k
Lesson 2.4
Even with all of the built in mechanisms we have to maintain
glucose homeostasis there is still a normal range in which
glucose rises and falls in the blood. After we eat, the extra
energy from food is stored as glycogen in the muscles and the
liver, and as triglycerides in the adipose tissue. Between meals,
these stores of energy are broken down, providing energy until
you eat again. It is normal for blood glucose concentrations to
Figure 1: The symptoms of
slowly decline a bit between meals, but severe drops in glucose
low blood sugar.
are rare in healthy individuals. Some symptoms of low blood
sugar are hunger, feeling jittery, nauseous, confused or light
headed. More symptoms are shown in Figure 1. Some health conditions can lead to dangerously low
levels of glucose, including diabetes and excessive alcohol intake. Because the brain relies on glucose for
energy, not having adequate blood glucose levels will stress the brain. Having excessively low glucose
concentrations in the blood for long periods of time can lead to seizures, fainting, coma or even death.
1. What happens to the blood glucose
concentrations of a healthy
individual between meals?
aa. It rises slightly.
bb. It drops to a dangerously low
level.
cc. It slowly drops, but is not
dangerous.
dd. It remains constant.
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LESSON READINGS
The pancreas senses low blood glucose
DEFINITIONS OF TERMS
Glucagon — A hormone formed
in the pancreas that promotes
the breakdown of glycogen to
glucose.
Gluconeogenesis — A
metabolic pathway that results in
the generation of glucose from
other carbon substrates, such as
glycerol and amino acids.
For a complete list of defined
terms, see the Glossary.
Specific hormones are
released from your
Low$Blood$Glucose$
Glucagon$Signals$the$Liver$
digestive system when
Promotes$Glucagon$Release$
$to$Un;Store$Glucose$$
energy stores are full or
are dropping. Recall from
Lesson 2.3 that when
Insulin$
glucose levels increase the
pancreas releases insulin.
Similarly, the pancreas
Pancreas(
Liver(
will sense when the blood
glucose levels are low
Figure 2: Low levels of glucose stimulate the pancreas to make
glucagon that signals the liver to un-store glucose.
and send the message to
storage organs that more
glucose is needed in the
blood. The pancreas sends this signal in the form of glucagon, a hormone made out of amino acids.
Glucagon opposes the actions of insulin, and stimulates the production and release of glucose. Therefore,
the result of glucagon being released from the pancreas is an increase in glucose concentrations in the
blood.
In addition to insulin and glucagon, hormones are released from other parts of your digestive system
that send signals to the brain regarding the state of energy storage. This is an intricate process involving
several organs and signaling systems. We will learn a lot more about these hormones, and how your body
tells your brain that it is time to start and stop eating in Unit 3.
The liver is the master regulator of blood glucose
We learned in Lesson 2.3 that the liver is the master regulator in determining how glucose will be stored.
The liver is also the organ that delivers glucose to the blood when blood glucose concentrations get too
low. The liver will break down its glycogen stores and release them into the blood. Remember that the
muscle cannot export its glucose, so even if the muscle has leftover glycogen to break down into the
glucose, that glucose can only be used in the muscle.
Wo r k b o o k
Lesson 2.4
2. What is the pancreas' response
when more glucose is needed in the
blood?
aa. It releases glucagon.
bb. It releases insulin.
cc. It releases glucose.
dd. It releases fatty acids.
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LESSON READINGS
The conundrum: How does the energy from
fat and amino acids reach the brain?
Glucose (Blood) If every organ in our body could use fat or
amino acids for energy then we would not
need to maintain a steady concentration of
blood glucose. We know that this isn’t the case,
because both the brain and the red blood cells
rely on glucose as their energy source. To get
around this problem, the liver can make new
glucose to release into the blood from the carbon
in amino acids and triglycerides, a process
called gluconeogenesis (‘gluco’ = glucose,
‘neo’ = new, ‘genesis’ = generation).
Gluconeogenesis Amino Acids Triglycerides Figure 3: Only the liver can make
glucose from fat and protein through
gluconeogenesis.
Converting stored energy into glucose
Because the brain normally relies on glucose
for energy, there must be a constant supply of
glucose into the blood stream even when other
tissues are using fatty acids or amino acids as
their energy source. When glycogen stores are
not enough, the liver will make new glucose to
export into the blood through gluconeogenesis.
Figure 4: Un-storing energy: triglycerides
from adipose cells and amino acids from
muscle cells are the batteries.
Wo r k b o o k
Lesson 2.4
Counting carbons: from Acetyl CoA to
glucose
Gluconeogenesis makes glucose by starting
with an intermediate in the citric acid cycle and
undergoing several reactions to yield glucose. Another way to think of gluconeogenesis is as the reverse
of glycolysis. The two carbons in acetyl CoA can be added to other intermediates in the citric acid cycle
that contain four carbons, resulting in a six-carbon molecule of glucose.
3. Which of the following substrates
can be used for gluconeogenesis?
aa. Amino acids.
bb. Glycerol.
cc. Acetyl CoA.
dd. All of the above.
4. How are triglycerides used as energy
in the body?
aa. Fatty acids are used in the citric
acid cycle in every cell of the
body.
bb. Fatty acids are used for energy
in most cells, glycerol is used for
gluconeogenesis in the liver.
cc. The fatty acids must first be
converted to glucose.
dd. Only the adipose tissue uses
triglycerides for energy.
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LESSON READINGS
Glucose is created from amino acids
DEFINITIONS OF TERMS
Lipolysis — The metabolic
breakdown of lipids to release
energy.
Urea — A nitrogen-containing
compound mostly made from
degraded proteins.
For a complete list of defined
terms, see the Glossary.
The intermediates in the citric acid cycle
that are added to acetyl CoA to make
glucose are made from amino acids.
Remember that amino acids are made
from the carbon chain and an amino
group; the nitrogen-containing amino
group of the amino acid is broken off,
leaving the carbon skeleton. This results
in free nitrogen, which can be harmful
to our cells if left floating in the blood.
The liver will package this nitrogen up
as urea, which is excreted in urine.
Physicians can determine if a patient
is breaking down excesses amino
acids because they will have high urea
concentrations in their urine.
Muscle Glucose Acetyl CoA Amino acids Urea Citric acid cycle Figure 5: The liver can make glucose from acetyl
CoA and the carbon skeletons of amino acids, in a
process called gluconeogenesis. This creates extra
urea, which is excreted in the urine.
The carbons of amino acids are required for the synthesis of new glucose, and amino acids used to build
muscles are the first to be broken down when dietary amino acids run out. Because of this, whenever
your body is in a state of needing to undergo gluconeogenesis, your muscles are most likely being broken
down to provide amino acids.
Energy is released from Fat
Glucose Acetyl CoA Citric acid cycle Triglyceride Adipose Lipolysis
Amino acids Wo r k b o o k
Lesson 2.4
Figure 6: Triglycerides stored in the adipose
tissue are broken down to acetyl CoA by lipolysis. Amino acids are used as intermediates in the
citric acid cycle.
As triglycerides are metabolized in a process
called lipolysis (‘lipo’ = lipid, ‘lysis’ = to break)
they produce one molecule of glycerol that
can be used to make glucose, and three fatty
acids that are used to generate ATP. The
process of producing ATP from fatty acids
was discussed in Lesson 2.2. The carbons of
the fatty acids chains are broken off, two at
a time, and converted into acetyl CoA. This
acetyl CoA is used in the citric acid cycle to
generate NADH and FADH2 for the electron
transport chain. The three carbons of glycerol
are then used directly in the synthesis of new
glucose.
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LESSON READINGS
The type of energy store you use depends on how long
you have been fasting
The body’s response to fasting is largely a function of how long one has gone without eating. For this
reason we will discuss fasting in three stages: The first hours of fasting, 1-7 days of fasting, and more than
a week of fasting. We can use these stages as a guideline, however each person’s metabolism and body
is unique, therefore the times listed here may vary for each individual.
0-12 hours after
eating
1-7 days after
eating
One week after
eating
Wo r k b o o k
Lesson 2.4
Components to be
broken down:
Liver and muscle
glycogen stores.
Triglyceride stores in
adipose
Broken down
into:
Glucose
Body protein
Amino acids
Used for:
Energy for the brain, red blood cells and
other cells
Fatty acids and Fatty acids: energy for cells other than
glycerol
the brain and red blood cells; Glycerol:
gluconeogenesis
Body protein
Amino acids
Intermediates in citric acid cycle;
carbons of some amino acids used for
gluconeogenesis
Triglyceride stores in Fatty acids and Fatty acids: energy for cells other than
adipose
glycerol; ketone the brain and red blood cells; Glycerol:
bodies
gluconeogenesis (as long as amino
acids are available)
Ketone bodies: energy for the brain
Gluconeogenesis until there is no spare
protein to break down
Triglyceride stores in Fatty acids and Fatty acids and glycerol: energy for cells
adipose
glycerol; ketone other than the brain and red blood cells;
bodies
Ketone bodies: energy for the brain
Figure 7: This table outlines the different source of energy throughout the stages of fasting and
starvation.
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LESSON READINGS
0-12 Hours after eating
Figure 8: In short term fasting the
glycogen and proteins go first.
In the first few hours after eating the body will use its shortterm energy stores, which include glucose from glycogen
and stores of triglycerides. As the fast progresses, the liver
will exhaust its stores of glycogen and rely on gluconeogenesis. The body will begin to breakdown lean muscle
mass to free up amino acids that can be used to make
new glucose for the brain and the red blood cells. At the
same time gluconeogenesis is occurring, triglycerides
will be released from adipose stores to provide energy to
tissues other than the brain and the red blood cells.
1-7 Days after eating
If a person is mostly sedentary, their glycogen stores will last about
2 days. The amount of glycogen you can store is related to how
muscular you are. A more muscular person can store more glycogen,
but the higher lean muscle mass also means that more glucose will
be used to maintain those muscles. Therefore even a body builder
can’t last a week on their glycogen! After the glycogen stores have
been exhausted new glucose still needs to enter the blood stream for
Figure 9: In long-term
the brain and the red blood cells. The liver will begin to rely more on
fasting proteins and fats
are used.
amino acids for gluconeogenesis. Glycerol from triglycerides can be
used to make new glucose, but this can only occur as long as there
is enough spare amino acids that can be used alongside the glycerol
for gluconeogenesis. Unfortunately, only a limited amount of amino acids can be broken down for energy
purposes because amino acids are used to build important structural elements in our cells. If we were to
use all of our amino acids up for energy, we would be digesting our own tissues – which is not beneficial!
Wo r k b o o k
Lesson 2.4
After the expendable amino acids are used up, the body turns to our fat stores as the primary energy
source. If triglycerides become the only energy source available, the brain will start to use a metabolite
of lipolysis called ketone bodies. Ketone bodies will pass into the brain to be used in the citric acid cycle.
One of the waste products of ketone bodies will be excreted in the urine and the breath, and smells sweet.
Because of this, if someone’s body is breaking down fatty acids into ketone bodies for energy, their breath
will smell sweet, a phenomenon called 'ketone breath'. The brain will start using ketone bodies for energy
after only about 3 days of fasting, and the amount of ketone bodies that the brain relies on increases as
the fast continues.
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LESSON READINGS
By the end of the first week of fasting metabolism begins to slow down, and a person will start to feel
extremely fatigued. By slowing down the metabolism, cells will use less energy and the lifespan is
prolonged.
After one week without eating
At this point in fasting, the only energy source available is the triglycerides stored in adipose tissue. The
amount of time a person can live without eating depends on the amount of their adipose tissue stores.
Typically, the body can survive about three weeks before breaking down vital proteins in the muscles and
organs to use as energy. Once this process begins, fatality is near.
A quick review of today’s material
Figure 10: Each of the organ’s roles
during fasting.
Wo r k b o o k
Lesson 2.4
Using the figure to the left (Figure 10) we can
locate the organ or tissue in which each metabolic
process we’ve discussed today is occurring. The
pancreas senses low blood glucose and secretes
glucagon, which sends a message to the liver,
telling it to export more glucose into the blood.
The liver will export glucose from its own glycogen
stores into the blood. The muscles break down
glycogen into glucose to use for their own energy
needs, and secrete amino acids into the blood from
broken down proteins. The adipose tissue releases
fatty acids and glycerol. The liver will then take up
amino acids and triglycerides and secretes new
glucose into the blood from gluconeogenesis. As
always, the brain uses glucose, while the kidneys
are busy excreting the extra urea that is being
produced from the breakdown of amino acids.
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STUDENT RESPONSES
We have now discussed the body’s response to fasting. What might the body’s reaction be if you were to stop eating
carbohydrates completely, and no glucose was coming into the blood from the diet? How might this response differ from
fasting?
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Remember to identify your
sources
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Wo r k b o o k
Lesson 2.4
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TERMS
TERM
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 2.4
DEFINITION
Fasting
A state of abstinence from all food or drinks that provide calories.
Glucagon
A hormone formed in the pancreas that promotes the breakdown of glycogen to glucose.
Gluconeogenesis
A metabolic pathway that results in the generation of glucose from other carbon substrates, such as glycerol
and amino acids.
Lipolysis
The metabolic breakdown of lipids to release energy.
Urea
A nitrogen-containing compound mostly made from degraded proteins.
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