Objectives

At the end of this lecture you must be able

to;

Define glycogenolysis

List the enzymes involved in glycogenolysis pathway

Know the role of each enzyme involved

Know the pathway of glycogenolysis

Know the Inborn errors of glycogen metabolism

Review on glycogen
In which type of biomolecule does
glycogen belong?
In which class of the mentioned
biomolecule is glycogen?
What are the monomers of glycogen?
Which bond (s) are in a glycogen
molecule?
Where is glycogen stored in man?
Introduction
Glycogen is a polymer of glucose
residues linked mainly by α-1, 4
glycosidic linkages.
 There are α-1, 6 linkages at branch
points
The chains and branches are longer as
shown.

Structure of glycogen
Introduction cont’d
Glycogen is the major storage form of carbohydrate in
animals .
Mainly stored in liver and muscles
Mobilized as glucose whenever body tissues require.
Definition of (glycogenolysis)
Glycogen + lysis = Glycogenolysis
The word lysis means degrade/break
Glycogenolysis Simply refers to degradation /
breaking down of glycogen
Stages of glycogenolysis
1. Shortening of chains
2. Removal of Branches
3. Lysosomal Degradation of Glycogen
 •Glycogen phosphorylase cleaves the α-1, 4 glycosidic
bonds between the glucose residues at the non reducing
ends of the glycogen by simple phosphorolysis.

•• This enzyme contains a molecule of covalently bound

pyridoxal phosphate required as a coenzyme,
• Glycogen phosphorylase is a phosphotransferase that
sequentially degrades the glycogen chains at their non
reducing ends until four glucose units remain in each chain
before a branch point.
 Shortening of chains cont’

•The resulting structure is called a limit dextrin and

glycogen phosphorylase cannot degrade it any further.
 The product of this reaction is Glucose 1 phosphate.

The glucose 1 phosphate is then converted to

glucose 6 phosphate by phosphoglucomutase.

• Conversion of glucose 6 phosphate to glucose

occurs in the Liver, Kidney and intestines by the
action of Glucose 6 phosphatase. This does not
occur in the skeletal muscle as it lacks the Enzyme.
•The transferase activity removes the terminal 3 glucose
residues of one branch and attaches them to a free C4 end of
the second branch.
•The glucose in α-(1,6) linkage at the branch is removed by
the action of Glucosidase as free glucose.
•A debranching enzyme also called Glucantransferase which
carries out two activities, Glucantransferase and
Glucosidase.
A small amount of glycogen is continuously
degraded by the lysosomal enzyme α-(1, 4)
glycosidase (acid maltase).
The purpose of this pathway is unknown.
However, a deficiency of this enzyme causes
accumulation of glycogen in vacuoles in the
cytosol, resulting in a very serious glycogen storage
disease called type II (Pomp’s disease),
Summary of Glycogenolysis
Enzymes involved
Glycogen phosphorylase
phosphoglucomutase.
Glucose 6 phosphatase.
Glucosidase
Glucantransferase
lysosomal enzyme α-(1, 4) glycosidase (acid maltase).
. Inborn errors of glycogen metabolism
 Are a group of genetic diseases that result from a defect in an enzyme required for either
glycogen synthesis or degradation.

 They result in either formation of glycogen that has an abnormal structure or the
accumulation of excessive amounts of normal glycogen in specific tissues.
 A particular enzyme may be defective in a single tissue such as the liver or the defect may
be more generalized, affecting muscle, kidney, intestine and myocardium.

 The severity of the diseases may range from fatal in infancy to mild disorders that are not
life threatening.
 Some of the more prevalent glycogen storage diseases are the following.
 Table of Glycogen Storage Diseases
Type: Enzyme Affected Primary Manifestations
Name Organ

Type 0 glycogen synthase Liver Hypoglycemia and early death,

Type Ia: von glucose-6-phosphatase liver hepatomegaly,

Gierke's Kidney failure,
fatty liver,
hyperlacticacidimia and severe
hypoglycemia

Type II: lysosomal a-1,4- skeletal and muscular dystrophy, severe

Pompe's glucosidase, lysosomal Cardiac cardiomegaly,early death.
acid muscle
a-glucosidase acid maltase

Type V: muscle phosphorylase skeletal Muscle excercise-induced

McArdle's muscle cramps and pain, myoglobinuria
Questions cont’d
How does Glycogenolysis aid in regulation of
blood glucose levels?
Ans

Glycogenolysis is the degradation of glycogen stores.

This occurs in the Liver in the Fasting State, and
releases glucose into the circulation (for RBC - only
source of energy, and the brain - Gluc is primary
source of energy)
Questions cont’d
How is Glycogenolysis used in skeletal muscle?
Glycogenolysis occurs in skeletal muscle during
exercise (can only be used by muscle)
Produces Glucose from Glycogen, which is then
oxidized through Glycolysis
Questions con’d
How does reciprocal regulation affect
Glycogenolysis during Fasting State?
Glycogenolysis is stimulated, and Glycogenesis is
inhibited (Avoiding Futile Cycling)
*the opposite occurs during the Fed State
Questions cont’d
Once the body goes into fasting state, how long
until the Liver's Glycogen stores are depleted
(and Gluconeogenesis is the only source of
Glucose)?
24 hours
In Glycogenolysis glucose residues are removed
form what end of the glycogen molecule?
The non-reducing ends
Questions cont’d
What enzyme is responsible for breaking the
alpha (1,4) bonds between glucose chain
residues? What is used in the process? What co-
factor is required? What is the product?
Glycogen Phosphorylase (uses Pi)
Co-factor: Pyridoxal Phosphate (PLP)
Product: Glucose-1-Phosphate (92% of glucose in
glycogen molecule)
What enzyme is missing in the following conditions?
Condition Missing enzyme
Type 1: Von Gierke's Disease Glucose-6-phosphatase (only in liver, causing Hypoglycemia
&Hematomegaly)
 
 

Type 2: Pompe's Disease alpha-1,4-Glucosidase (lysosomal, very sever clinical features)

   

Type 3: Cori/Forbes Disease Debranching Enzyme (mild hypoglycemia & hepatomegaly)

Type 4: Andersen's Disease Branching Enzyme (Hepatomegaly, Cirrhosis, Liver failure, death by 2
years)
 
 

Type 5: McArdle's Disease Glycogen Phosphorylase (Fatigability, muscle cramps, muscle has
increased glycogen)

Type 6: Her's Disease Glycogen Phosphorylase

   
 Lets answer the questions below
Define glycogenolysis
Outline the stages in glycogenolysis
Outline the enzymes involved at each stage of glycogenolysis
Show the major products produced at each stage
Trace the pathway of glycogenolysis
What are the major Inborn errors of glycogen metabolism.
Why does the conversion of glucose 6 phosphate to glucose not
occur in skeletal muscles?
Briefly talk about the following diseases Type 0, Type Ia: von
Gierke's, Type II:Pompe's and Type V:McArdle's.
Assignment
1. Glucose-1-phosphate liberated from glycogen
cannot be converted into free glucose in
(A) Liver (B) Kidneys (C) Muscles (D) Brain
2. If glucose-1-phosphate formed by
glycogenoloysis in muscles is oxidized to CO 2 and
H2O, the energy yield will be
(A) 2 ATP equivalents (B) 3 ATP equivalents
(C) 4 ATP equivalents (D) 8 ATP equivalents
Assignment cont’d
3. Glycogen is converted to glucose-1- phosphate by
(A) UDPG transferase (B) Branching enzyme
(C) Phosphorylase (D) Phosphatase
4. The tissues with the highest total glycogen content
are
(A) Muscle and kidneys
(B) Kidneys and liver
(C) Liver and muscle
(D) Brain and Liver
Assignment cont’d
5. Glycogen structure includes a branch in
between–glucose units:
(A) 6–12 (B) 8–14
(C) 6–10 (D) 12–18
 
6. McArdle’s disease is due to the deficiency of
(A) Glucose-6-phosphatase
(B) Phosphofructokinase
(C) Liver phosphorylase
(D) muscle phosphorylase
Done
Stay safe
Thanks Read hard
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