Glycogen metabolism

2nd year rehapilitation

Lecture 7
Objectives
1. State the structure, function and importance
of glycogen.
2. Identify the glycogenesis and it’s steps.
3. Discuss the steps of glycogenolysis.
4. Explain the regulation of glycogenesis &
glycogenolysis.
5. Describe the Glycogen storage disease (GSD)
and it’s types.
• Importance of glycogen:
– Excess dietary glucose is stored as glycogen mainly in liver and
muscles.
– The body can use glycogen to obtain glucose rapidly between
meals or during muscular exercise.

• Structure of glycogen:
– Glycogen is a hohopolysaccaride formed of glucose units bound
by
• α 1-4 glucosidic linkage to form 1 branch (straight chains )
• and by α 1-6 glucosidic linkage (to form branched points).

– The branches contain from 8 – 12 glucose residues.

– Glycogen (together with enzymes of synthesis and degradation)
is present in the form of granules in the cytoplasm

– Glycogen metabolism includes glycogenolysis and glycogenesis

Function of Glycogen:
In Muscles: To supply glucose within the
muscle that undergoes glycolysis to produce
energy during contraction.

In Liver: To maintain blood glucose level

especially between meals and in fasting up to
12 – 18 hours.

After 12 – 18 hours, fasting liver glycogen is

depleted, whereas muscle glycogen is depleted
after muscular exercise.
 Supplies glucose for glycolysis

Between meal and short

fasting 12-18hours
Liver glycogen depleted Muscle glycogen depleted
after 12-18 hrs fast after excersise
G6p phosphotase
 Glycogenesis
• Definition: Synthesis of Glycogen from glucose
• Where : Mainly liver and muscle cells
• Site: Cytoplasm
• Steps: a)Synthesis of UDPG (uridine diphospho -glucose)
b) Synthesis of Glycogen from UDPG
 Steps of Glycogen Synthesis

1.Initiation (formation of glucose donor):

– UDP glucose is the glucose donor and it is formed
from glucose 1- phosphate and UTP
2. Elongation of glycogen chain:
– By Glycogen synthase enzyme which uses UDP-
glucose as substrate and add it to glycogen primer
forming α 1- 4 glycosidic linkage.
3.Formation of glycogen branches:
– By branching enzyme which transfers 6 glucose
residues from terminal end to form a branching point
by α 1- 6 glycosidic linkage .
Steps:
1.Initiation (formation of glucose
donor):
2- Synthesis of Glycogen from UDPG: (Elongation and
formation of branches)

Requires 2 enzymes , Glycogen Synthase and

Branching Enzymes
 Elongation

initiation

Formation of
branches
 GLYCOGENOLYSIS
• Definition: Break down of glycogen to form glucose-1-P,
which is converted to glucose-6-p
• Where : Mainly liver and muscle cells
• Site: Cytoplasm
Steps of GLYCOGENOLYSIS:

There are two stages of glycogenolysis:

Stage 1 (shortening of glycogen chain):
By the enzyme glycogen phosphorylase which
removes single terminal glucose molecule (by
breaking α 1-4 glucosidic linkage) in the form of
(glucose-1-phosphate)
Stage 2 (removal of the branches):
Debranching enzyme breaks α 1-6 glucosidic link at
branching points
Fate of glucose 1-phosphate in liver and muscle

• The glucose-1-phosphate is converted to glucose -6-

P by mutase enzyme

• In the liver and kidney glucose-6-P is converted to

glucose, by the action of glucose-6-phosphatase for
maintaining blood glucose levels.
• In skeletal muscle (which lack glucose-6-
phosphatase) glucose -6- P will be oxidized in the
glycolytic pathway to get energy for the muscle.
 Regulation of glycogenolysis
(Glycogen phosphorylase)

1-Covalent modification by phosphorylation :

– Glucagon: activates the enzyme by phosphorylation
– Calcium: activates the enzyme by phosphorylation
2- Allosteric regulation:
– In muscles: AMP (low energy level of cell)
allosterically activates phosphorylase enzyme
– In the liver: glucose inhibits the enzyme.
 Regulation of Glycogen Synthesis
(Glycogen synthase)
• Hormonal regulation by phosphorylation:
– Insulin activates the enzyme by dephosphorylation
– Glucagone and epinephrine inhibit the enzyme by
phosphorylation

• Ca++ inhibits the enzyme by phosphorylation.

• Allosteric regulation:
– The enzyme is allosterically activated by glucose-6-
phosphate and ATP
 Allosteric and hormonal Regulation of
Glycogen metabolism

ATP

- Glucagon
Glucagon +
Insulin
+

ATP

Glucagon + Glucagon
_ -
_ Ca++
Insulin
+
 Glycogen storage disease (GSD)
Glycogenosis
• Inherited defects
• Difecency in one or more of the enzymes involved in the synthesis and
degradation of glycogen.
• Liver is the most affected,
• Heart and muscle glycogen metabolism can also be affected.
Types of GSD :
There is different types of GSD- depend on enzyme defect

Von Gierke Disease (Type 1)

• Known as GSD Type I
• Most common form
• Deficiency in Glucose-6-Phosphatase
(Glucose 6 phosphate ----------→ Glucose)
• Defect in glycogenolysis and
gluconeogenesis
• Deficiency of the enzyme occures in the
liver, kidney and intestinal mucosa
 X
G6p phosphotase
 Manifestation of von Gerick disease

• Fasting hypoglycemia (severe).

• Hyperlipidemia, fatty liver & hepatomegally.

• Hyperuricemia or gout (high plasma uric acid level), accumulation of G-6-P

results in stimulation of HMP and increases the synthesis of
phosphoribosylpyrophosphate (PRPP) and purine nucleotides. The latter
produce uric acid by catabolism.

• Lactic acidemia because liver cannot use lactate for glucose synthesis.

• Progressive renal disease.

• Growth retardation.

• Increased glycogen stored in organs

Other Types of GSD

Type name Enzyme affected Primary organ Manifestation

Type II Lysosomal α1,4- Liver, heart, • Normal blood
Pompe’s glucosidase muscles glucose
• Severe
cardiomegaly
• Early death
Type V Muscle Skeletal muscle • Exercise-
Mc Ardle phosphorylase induced
cramps and
pain, but no
increase in
blood lactic
acid
• Myogloinuria
• High glycogen
level in muscle
 Recommended reading

• Lippincott’s illustrated reviews

biochemistry