2. Glycogen metabolism
Function of glycogen
Glycogen is the storage form of carbohydrates in the
human body.
The major sites of storage are liver and muscle.
1. The major function of liver glycogen is to provide
glucose during starvation.
When blood glucose level lowers, liver glycogen is
broken down and helps to maintain blood glucose level.
2. The function of muscle glycogen is to act as reserve
fuel for muscle contraction.
Muscle glycogen is depleted after prolonged exercise. 2
3. After taking food, blood sugar tends to rise,
which causes glycogen deposition in liver.
About 5 hours after taking food, the blood
sugar tends to fall. But, glycogen is lyzed to
glucose so that the energy needs are met.
After about 18 hours fasting, most of the
liver glycogen is depleted, when depot fats
are hydrolyzed and energy requirement is
met by fatty acid oxidation.
3
5. Glycogenolysis
It is intracellular breakdown of glycogen to form
G-1-P which is converted to G-6-P.
Site and steps:
Its main site is the cytosol of liver and muscles.
It is catalyzed by: glycogen phosphorylase and two other
enzymes.
5
6. 1- Glycogen phosphorylase:
The enzyme glycogen phosphorylase
removes glucose units one at a time from the
non-reducing end of the glycogen molecule.
The product is glucose-1-phosphate.
Phosphorylase sequentially attacks alpha-1,4
glycosidic linkages, till it reaches a branch
point.
It cannot attack the 1,6 linkage at branch
point. 6
8. 2- Debranching needs two enzymes
With the help of glucan transferase and
debranching enzyme (alpha-1,6-
glucosidase), the branching point is also
hydrolysed.
This glucose residue is released as free
glucose.
With the removal of branch,
phosphorylase enzyme can now proceed
with its action. 8
10. 3- Phosphoglucomutase:
Phosphorylation reaction produces glucose-
1-phosphate while debrancher enzyme
releases glucose.
The glucose-1-phosphate is converted to
glucose-6-phosphate by phosphglucomutase.
10
11. 4- Glucose-6-phosphatase in liver
Next, hepatic glucose-6-phosphatase
hydrolyzed glucose-6-phosphate to
glucose.
The product of hepatic glycogenolysis
is free glucose.
The product of hepatic glycogenolysis
is free glucose, which is released to the
blood stream. 11
12. 5- Muscle lacks Glucose-6-phosphatase:
But muscle will not release glucose to the blood
stream, because muscle tissue doesnot contain the
Glucose-6-phosphatase.
The energy yield from one glucose residue derived
from glycogen is 3 ATP molecules, because no ATP
is required for initial phosphorylation of glucose
(step 1 of glycolysis).
If glycolysis starts from free glucose only 2 ATPs are
produced.
12
13. Glycogenesis
The glycogen synthesis occurs by a pathway distinctly
different from the reversal of glycogen breakdown.
It is the intracellular synthesis of glycogen from glucose.
Site and steps:
The main site is the cytosol of liver and muscle cells. In the
liver it forms 8-10% of its wet weight and in muscle it forms
1-2% of its wet weight. Most other cells may store minute
amounts. 13
14. 1- Activation of Glucose:
UDP glucose is formed from glucose-1-phosphate
and UTP (uridine triphosphate) by the catalytic
activity of UDP-glucose pyrophosphorylase.
UDP-glucose-
pyrophosphorylase
Glucose-1- -------------------------------→ UDP-glucose
Phosphate
+ +
UTP PPi
14
15. 2- Glycogen synthase:
In the next step, activated glucose units are
sequentially added by the enzyme glycogen
synthase.
The glucose unit from UDP-glucose is transferred to
a glycogen primer molecule.
Glycogen primer (n)----------→ Glycogen (n+1)
+ +
UDP-glucose UDP
15
16. The glucose unit is added to the nonreducing
(outer) end of the glycogen to form an alpha-
1,4-glycosidic linkage and UDP is liberated.
The primer is essential as the acceptor of the
glycosyl unit. The glycogen primer is formed by
glycosylation of glycogenin (a dimeric protein).
This molecule acts as the glycogen primer to
which glucose units are added by glycogen
synthase.
16
17. 3- Brancher enzyme
A branching enzyme is needed to create
the alpha-1,6 linkages.
To this newly created branch, further
glucose units can be added in alpha-1,4
linkage by glycogen synthase.
Branching makes the molecule more
globular.
17
19. Regulation
The key enzyme for glycogenolysis is
phosphorylase, which is activated by
glucagon and adrenaline, under the stimulus of
hypoglycemia.
The key enzyme for glycogen synthesis is
glycogen synthase, the activity of which is
decreased by adrenaline but is enhanced by
insulin, under the stimulus of hyperglycemia.
19
20. Glycogen storage diseases
These are inborn-errors of metabolism; the
word is coined by Garrod in 1908.
Glycogen Storage Disease Type-I:
It is also called Von Gierke’s disease. Most
common type of glycogen storage disease is
type I.
20
21. Incidence is 1 in 100,000 live births.
Glucose-6-phosphatase is deficient.
Fasting hypoglycemia that does not respond to
stimulation by adrenaline. The glucose cannot be
released from the liver during over night fasting.
Hyperlipidemia, lactic acidosis and ketosis.
Glycogen gets deposited in liver. Massive liver
enlargement may lead to cirrhosis.
Children usually die in early childhood.
Treatment is to give small quantity of food at
frequent intervals.
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