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Learning Objectives:
What are the steps glycogen breakdown and
synthesis?
What are the central enzymes in glycogen
mobilization and synthesis?
How are glycogen mobilization and synthesis
coordinated?
What are the different glycogen storage diseases
and why is biochemical understanding of each is
important?
Glycogen Granules
Abundant in liver of well-fed animals but
absent after 24 hrs of fasting; or after heavy
exercise
Granules also contain the enzymes that
catalyze its formation and use.
STORAGE
The polymeric nature of glycogen allows Muscle glycogen is a fuel reserved for the
energy to be sequestered without the production of ATP within that tissue
problems of osmotic effects that glucose whereas liver glycogen is a glucose reserve
would cause. for the maintenance of blood concentration
Primarily stored in the MUSCLE and LIVER
In humans, liver glycogen stores are typically
adequate for up to 12 hrs. without the support
of gluconeogenesis
Glycogen Storage
Glycogen concentration is higher in the liver
than in muscle, but
More glycogen is stored in the skeletal muscle
because there are more skeletal muscles in
the body than there is liver tissue.
In the liver, glycogen synthesis and
degradation are regulated to maintain blood-
glucose levels as required to meet the needs
of the body as a whole.
In the muscle, these processes are regulated
to meet the energy needs of the muscle itself.
Glycogen - storage form of fuel
o Composed of glucosyl residues, mostly
linked together by - 1,4 glycosidic Glycogen Breakdown Requires Several Enzymes
linkages. Branches arise from frequent Breakdown of glycogen to provide glucose 6-
- 1,6 glycosidic linkages phosphate for further metabolism requires
Glycogen Tree - branches at every 4th four enzyme activities:
glucosyl residue within the more central core o One to degrade glycogen
of the molecule and less in the outer region o 2 enzymes to remodel glycogen so that
it remains a substrate for degradation
o One to convert the product of glycogen
breakdown into a form suitable for
further metabolism
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Glycogen Degradation
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The cooperative & repetitive action of
phosphorylase & debranching enzyme results
in complete breakdown of glycogen to glucose
-1- PO4 & glucose.
Phosphoglucomutase converts glucose 1-
phosphate into glucose 6-phosphate so that it
can enter the metabolic mainstream.
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GLYCOGEN SYNTHESIS
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Glycogen Synthase Catalyzes the Transfer of
Glucose from UDP-Glucose to a Growing Chain
Glycogen Synthase transfer the activated
glucosyl moiety of UDP glucose to the carbon
4 of a glucosyl residue of the growing chain to
form a new glycosidic bond at the hydroxyl
group of C1of the activated sugar.
The reducing end of glucose (C1) is always
added to the non- reducing end (C4) of a
glucosyl residue of the glycogen chain
A Branching Enzyme Forms -1,6 Linkages Branching increases the rate of glycogen
Glycogen synthase cannot form the 1,6- synthesis and degradation
glycosidic linkages
Once an amylose chain of at least 11 residues
has been formed, a branching enzyme,1,4-
glucan branching enzyme removes a block of
about 7 glucosyl residues from a growing chain
and transfer it to another chain to produce an
-1,6 linkage.
The new branch has to be introduced at least
4 glucosyl residues from the nearest branch
points
The creation of the highly branched structure
of glycogen requires the concerted efforts of
glycogen synthase and branching enzyme.
Branching is important because it increases
the solubility of glycogen.
Branching creates a large number of terminal
residues, the sites of action of glycogen
phosphorylase and synthase.
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Glycogenin is Required as a Primer for Glycogen 3. Fat cannot be converted to glucose to
Synthesis maintain blood glucose levels required by the
brain
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A Biochemical Understanding of Glycogen-Storage
Diseases is Possible
Edgar von Gierke described the 1st glycogen
storage disease in 1929.
o A patient with this disease had a huge
abdomen caused by a massive enlargement
of the liver.
o There is pronounced hypoglycemia
between meals.
o The blood glucose does not rise on the
administration of epinephrine and glucagon
o An infant with this disease may have
convulsions because of low blood glucose
level
o The enzymatic defect in von Gierke
disease was elucidated in 1952 by Carl and
Gerty Cori.
o Glucose 6-phosphatase is missing from the
liver of a patient with this disease.
o This finding was the first demonstration of
an inherited deficiency of a liver enzyme.
o The liver glycogen is normal in structure
but present in abnormally large amounts
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o The absence of glucose 6-phosphatase in o The presence of excess G 6-P triggers an
the liver causes hypoglycemia because increase glycolysis in the liver, leading to
glucose could not be formed from G 6-P high lactate and pyruvate in the blood.
o The G 6-P does not leave the liver, o Patients with von Gierke disease also have
because it cannot cross the plasma an increase dependence on fat
membrane. metabolism.
o fasting hypoglycemia, lactic acidemia,
hyperlipidemia, & hyperuricemia with
gouty arthritis
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-END-
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