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Fasting Cycle in Skeletal Muscle and Brain

Victoria Do & Elizabeth Dauer


BIOL 3410

What happens to carbohydrate/fat/amino acid in the brain?


Glucose is considered the most important source of fuel to the bodys metabolism and
also serves as the primary sole fuel for the human brain. The brain requires a continuous supply
of glucose because it does not have the capacity to store fuels. It also uses an abundant amount of
energy due to maintaining the electrostatic potentials required for nerve impulse transmission.
The average brain consumes about 120 grams of glucose a day and is transported into the brain
cells by the glucose transporter GLUT3. Also, about seventy percent of the energy is used to
maintain the Na+ (sodium)/K+ (potassium) membrane potentials and also synthesizes
neurotransmitters (Berg, Tymoczko, & Stryer, 2002). But only under prolonged starvation does
the brain use another source of fuel rather than glucose.
During the prolonged starvation or fasting state, glucose consumption of the brain
decrease by twenty-five percent, and ketone body extraction increases correspondingly. Ketone
bodies are generated by the liver and partly replaces the glucose as fuel for the brain (Berg,

Tymoczko, & Stryer, 2002). In normal state, the glucose transporter has a low value of KM for
the glucose, meaning it is saturated under in most conditions. This allows the brain to be
provided with a constant supply of glucose. Unlike glucose and ketone, fatty acids do not serve
as a fuel for the brain. This is because they are bound to albumin in the plasma and do not
transverse the blood-brain barrier.
Table 30.2Fuel metabolism in starvation
Amount formed or consumed in 24 hours (grams)
Fuel exchanges and consumption

3d day

40th day

Glucose

100

40

Ketone bodies

50

100

All other use of glucose

50

40

Adipose-tissue lipolysis

180

180

Muscle-protein degradation

75

20

Glucose

150

80

Ketone bodies

150

150

Fuel use by the brain

Fuel mobilization

Fuel output of the liver

What happens to carbohydrate/fat/amino acid in the skeletal muscles?


When the body is in the fasting stage, your metabolism will adapt by making glucose turning
it into the alternative fuel to conserve energy. Glucose is a carbohydrate and is the most
important simple sugar in human metabolism (Berg, Tymoczko, & Stryer, 2013). Unlike the
brain, the muscles have stores of glycogen. A polysaccharide that is the main storage form of
glucose in the human cell. The glycogen is readily converted into glucose when needed for
immediate activities. So when the body is fasting, muscle tissue is degraded into amino acids and
the carbon skeletons are used for fuel. The muscle can also use glucose, fatty acids, and ketone
bodies for a source of energy.

One type of muscle in the human body are the skeletal muscles. They are built for aerobic
metabolism and prefer to use fat as a source of energy (Berg, Tymoczko, & Stryer, 2013). But
during the fasting state, the skeletal muscle release two types of amino acids called alanine and
glutamine. These two amino acids play a major role in metabolism and are presented in high
concentrations in blood plasma. In the fasting state, the muscle tissue lack the enzymes to
convert ammonia into urea (Berg, Tymoczko, & Stryer, 2002). Instead, alanine transaminase
transfers the amino group to pyruvate to form alanine. This then allows the muscle tissues to
produce a large amount of alanine by the transfer of pyruvate. Alanine is then released by the
muscle tissue into the blood stream where it is absorbed by the liver. Lastly, the pyruvate is
converted into glucose by gluconeogenesis and the amino group of alanine is converted into the
urea by the urea cycle (Berg, Tymoczko, & Stryer, 2013).

Figure 30.12Metabolic Interchanges between Muscle and Liver


Kidney in long term fasting
In the body, the major role of the kidney is to produce urine, which is a vesical for
excreting water-soluble waste products. It uses sugar glucose as the main source of energy and
can decrease by low food intake. The kidneys require large amounts of energy to accomplish the
reabsorption. During starvation, the kidney becomes an important site of gluconeogenesis and
may contribute as much as half of the blood glucose (Berg, Tymoczko, & Stryer, 2002). When
the kidney runs out of glucose in the fasting state, it then uses glucose storage glycogen. And

when glycogen runs out, the body will break down fat for energy. It is very important for the
kidney to have sufficient energy source because its last resort after using fat will be energy in
proteins. And when it gets to that point, the body will no longer be fasting, but starving and lead
to kidney failure.
Glycogen Breakdown by Phosphorylase and Phosphoglucomutase

(Berg, Tymoczko, & Stryer, 2013).


Allosteric Regulation of Phosphorylase:
Phosyphorylase exists in two forms: phosphorylase a and phosphorylase b (the less active
form). Both of these forms are in equilibrium between the tense and relaxed state, with the a
form favoring relaxed and b form favoring tense.
Skeletal muscles regulate the need for phosphorylase through allosteric inhibitors ATP and
glucose 6-phpsphatase which are at high levels when muscles are at rest and do not need to break
down glycogen (Berg, Tymoczko, & Stryer, 2013).

Skeletal muscles also utilize hormones (specifically derived from tyrosine) to covalently
modify phosphorylase b to phosphorylase a for quick degradation of glycogen when fuel is
needed (Berg, Tymoczko, & Stryer, 2013).

The exact mechanism of how epinephrine triggers conversion to phosphorylase a is


mediated by a G coupled protein receptor in plasma membrane of muscle cells. When
epinephrine binds to the transmembrane receptor, the coupled G (alpha stimulatory) protein is
converted from GDP to GTP, which dissociates from the beta and gamma subunits to activate
adenylate cyclase. Adenylate cyclase converts ATP to cyclic AMP, which phosphorylates and

activates protein kinase A, which phosphorylates and activates phosphorylase kinase.


Phosphorylase kinase ultimately activates phosphorylase a (Berg, Tymoczko, & Stryer, 2013).
Overview:
When fasting begins, insulin levels decrease and glucagon levels increase. The goal is to
maintain optimum glucose levels in the plasma for RBCs and for the brain. The goal is also to
use fatty acids from adipose tissue to make and release ketone bodies from the liver to supply
fuel for brain and RBCs. In the first few weeks of fasting the muscles get glucose from glycogen
breakdown from exercising muscle. Glycogen gets broken down into glucose-6-phosphate,
which gets converted to lactate. Lactate gets converted into glucose through the Cori cycle
involving the liver. Once all of glycogen is used, fatty acids are broken down into acetyl-coA in
the process of fatty acid oxidation. Acetyl-coA can then enter the TCA cycle, which is needed for
energy. The liver will make ketone bodies that can also be converted to acetyl-coA in the muscle,
which will go into the TCA cycle. Proteins are also in the muscle, which will be broken down
into amino acids. The amino acids are utilized in gluconeogenesis to form glucose. Around the
third week of fasting, muscles do not use ketone bodies anymore and they are left for the brain.
In the brain, within 1-2 days of fasting, glucose gets converted to pyruvate in the process of
glycolysis and pyruvate is converted to acetyl-coA for energy. Ketone bodies from the liver will
also be converted to acetyl-coA. But after a few weeks, there will be no glucose and ketone
bodies will be the only source to make acetyl-coA. When acetyl co A levels start to become high,
acetyl-coA starts inhibiting pyruvate dehydrogenase and pyruvate will not be converted into
acetyl-coA in a negative feedback mechanism. Therefore, the pyruvate level will go up and
pyruvate will get converted into alanine. Alanine can start gluconeogenesis, which will produce
free glucose, which the brain can use (Berg, Tymoczko, & Stryer, 2013).

References

Berg, J.M., Tymoczko, J.L., Stryer, L. (2002). Biochemistry. 5th edition. New York: W H
Freeman.
Berg, J.M., Tymoczko, J.L., Stryer, L. (2013). Biochemistry: A Short Course. 2nd edition. New
York: W H Freeman.

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