2. What is Glycogen
• Large, highly branched polymer of glucose
• Mainly contain α - 1—4 glycosidic bonds in straight
chain and α - 1 –6 glycosidic bonds at branch points
• Readily mobilized form of glucose
• Broken down when energy is needed.
3. Glycogen storage
• Animal polysaccharide synthesized when
• glucose is excess
• Stored in liver and muscle
• Liver store more glycogen than muscle , but
as muscle mass is greater than liver about Âľ of
total
• body glycogen is present in muscle.
• Extra cellular glycogen is very small
4. Why glycogen is stored?
• Buffer to maintain blood glucose level
• Provide glucose to brain - except in starvation
• In muscle required for strenuous activity
• Glycogen release glucose which can provide energy
in absence of oxygen
• Liver glycogen can export glucose and maintain blood
glucose level in fasting states
5. Glycogenesis
• Synthesis of glycogen from glucose
• Occurs in muscle and liver
• Steps
1. Activation of glucose
2. Initiation
3. Elongation
4. Branching of glycogen
6. Activation of GlucoseGlucose
Glucose -1-phosphate
UDP- Glucose
ATP
ADP
Glucokinase
Hexokinase
UTP
PPi 2Pi
UDPG pyro phosphorylase
Spontaneous hydrolysis of
phosphate bond Provides
reaction energy
Only energy cost in
glycogen synthesis
Glucose -6-phosphate
Phosphoglucomutase
7. Initiation of Glycogenesis
• Glucose unit is transferred
from UDP-Glucose to
glycogen primer called
glycogenin
• Glycogenin –
• dimeric protein, 37kd
• Protein-carbohydrate complex
• Glycosidic bond is formed
between C1 of glucose and
hydroxyl group of tyrosine
• UDP is released
OH
O-UDPOH
UDP
OOH
Glycogen synthase
Glycogenin
Glycogenin + Glucose
9. Elongation
• New glucosyl units are added to the Non-reducing
terminal of glycogen
• Active Glucosyl unit UDP-Glucose is transferred to the
hydoxyl group of C—4 forming α - 1—4 glycosidic
link
• Reaction is catalyzed by glycogen synthase
• Glycogen synthase is Key regulatory enzyme in
glycogen synthesis.
OOOOOO
GlucoseGlucoseGlucoseGlucose
10. Elongation
• Addition of new glucosyl unit in straight chain continue
till 11- 12 glucose grow in chain
• Branching enzyme is required to form the branch
• Branching enzyme : Amylo 1—4 -- 1—6
transglucosidase
• Branching enzyme transfer 6-8 glucose units on 6th
carbon to form α - 1 –6 branch
11. OOOOOO
Branching is important as more number
of glucose units Can be added
simultaneously
Similarly Glycogen phosphorylation can
release more glucose
Branching
15. Glycogenolysis
• Break down of glycogen
• Takes place in Liver and muscle cytosol
• Divided in to three phase
– 1. Release of G-1-P from glycogen
– 2. Remodeling of limit dextrin
– 3. Conversion of G-1-P to Glucose -6 – Phosphate
• Two major enzymes required
• 1. Glycogen phosphorylase
• 2. Glycogen debranching enzyme
17. (Glycogen ) n
(Glycogen ) n—1
Pi
Glycogen
phosphorylase
Glucose -1-P
1—4 glycosidic bonds
1—6 glycosidic bonds
Glucose -1-P
Action of Glycogen phosphorylase
18. Phase 1 Phosphorolysis
• Glycogen phosphorylase , A key enzyme in glycogen
breakdown
• Action:
• Phosphorylates glucose on non- reducing end of
glycogen branch
• Release glucose -1- Phosphate
• Limitation:
• Enzyme has limitation as it reaches the point 3-4
glucose remained in chain
• This forms limit glycogen
19. Action of debranching enzyme
• Shifts a block of three
glucosyl unit from outer
branch to other
• Exposes α 1—6 linkage
• α 1—6 Glucosidase or
debranching enzyme
hydrolyses α 1—6 bond
and releases free glucose
20. Action of debranching enzyme
• Exposed α 1—6 linkage
• α 1—6 Glucosidase or debranching enzyme
hydrolyses α 1—6 bond and releases free
glucose
Free Glucose
21. Action of phospho-gluco-mutase
enzyme
• Free glucose is phosphorylated
• Glucose -1-Phosphate is converted to Glucose -6-
Phosphate
Glucose -1- P
Glucose -6- P
Phosphoglucomutase
Free Glucose
Glucokinase
22. Energetics of glycogenesis and glycogenolysis
• One ATP for incorporating one Glucose 6 p in
glycogen
• 90% of glycogen molecules are released as
G-1-P which is converted to G-6-P without
any energy
• Glucose released from branch need one
ATP to form Glucose -6-P
23.
24. Glycogen storage diseases
• Group of inherited disorders characterized by
deficient mobilization of glycogen or deposition of
abnormal type or quantity of glycogen in tissues.
• Leads to liver damage or muscle weakness. Some
GSD resulting in early death.
• Though there are more than 10 type six are classical
type
25. Glycogen storage diseases
Disease type Enzyme
defect
Tissue
involved
Clinical
manifestations
Type I
Von Gierke’s
disease
Glucose 6
phaophatase
Autosomal
recessive
Liver and
mucosal cell
Glycogen
accumulates in liver
& renal cell,
Hypoglycemia,
lipidemia,
Ketoacidosis , Fatty
liver , early death
26. Glycogen storage diseases
Disease type Enzyme defect Tissue involved Clinical
manifestations
Type II
Pompe’s
disease
Lysosomal Acid
maltase
Autosomal
recessive
Heart, liver
Smooth and
skeletal muscle
Glycogen
accumulates
lysosome, muscle
hypotonia, death
due to heart
failure by 2yrs age
,
Muscle dystrophy
27. Glycogen storage diseases
Disease type Enzyme defect Tissue involved Clinical
manifestations
Type III
Cori’s disease
Limit
dextrinosis
Debranching
enzyme
Autosomal
recessive
Liver , Heart
and Muscle
Abnormal Glycogen
accumulates
Hepatomegaly,
hypoglycemia,
Progressive
myopathy, acidosis
Survive - adult life
28. Glycogen storage diseases
Disease type Enzyme defect Tissue involved Clinical
manifestations
Type IV
Andersen’s
disease
Amylopectin
osis
Branching
enzyme
Liver , Abnormal Glycogen
deposited, without
branch
Hepatomegaly,
splenogegaly,
hypoglycemia,
Progressive cirhosis
of liver ,
Survive - < 4 yrs
30. Glycogen storage diseases
Disease type Enzyme defect Tissue
involved
Clinical
manifestations
Type VI
Her’s disease
Liver
phosphorylase
Liver Glycogen
accumulation normal,
Splenomegaly, mild
hypoglycemia with
acidosis ,
31. Glycogen storage diseases
Disease type Enzyme defect Tissue
involved
Clinical
manifestations
Von Gierkes G6P L,H,M
Pompe’s AM L,H,M,
Cori’s DB L,H,M
Andersen’s B L
McArdle’s Mplyase M
Hwe’s LPlyase L