Glycogen is the major storage carbohydrate in animals and is stored primarily in the liver and skeletal muscle. Glycogenesis is the process of glycogen synthesis from glucose, which takes place in the cytoplasm of liver and muscle cells. Glycogenolysis is the breakdown of glycogen into glucose-1-phosphate, and is regulated by hormones like glucagon and insulin to control blood glucose levels. Deficiencies in enzymes involved in glycogen metabolism can cause glycogen storage diseases.

1. GLYCOGEN
METABOLISM
DR. FARHANA ATIA
ASSOCIATE PROFESSOR
DEPARTMENT OF BIOCHEMISTRY
NILPHAMARI MEDICAL COLLEGE, NILPHAMARI

2. GLYCOGEN
Glycogen is polymer of
glucose and major storage
carbohydrate in animal
Stored site
Skeletal muscle: Serve fuel
for muscle activity
Liver: maintain blood glucose
concentration in early stage of
fasting (12-18 hours)
Brain: modest amount

3. Liver glycogen Muscle glycogen
1. Amount
90 g [5% of tissue
weight -1.8 kg]
245 g [0.7% of tissue
weight- 35 kg]
2. Source
Dietary carbohydrate
& gluconeogenesis
Blood glucose & muscle
lactic acid
3. Turnover rate Rapid Slow
4. Maintenance of
blood glucose
concentration
Positive role
No role due to absence of
glucose-6-phosphatase
5. Fuel for muscle
activity
No role
Ready source of glucose-1-
phosphate for glycolysis

4. GLYCOGENESIS
Glycogenesis is the formation of glycogen from glucose
Substrate: Glucose as Glucose-1-phosphate
Product: Glycogen
Site: Liver, Muscle
Comp: Cytoplasm
Nature: Anabolic
Rate limiting enzyme: Glycogen synthase

5. Steps of Glycogenesis
Glucose is phosphorylated
to glucose-6-phosphate,
catalyzed by hexokinase
(muscle) and glucokinase
(liver)
Glucose-6-phosphate is
isomerized to glucose-1-
phosphate by
phosphoglucomutase

6. Steps of Glycogenesis
Glucose-1-phosphate reacts
with uridine triphosphate
(UTP) to form the active
nucleotide uridine
diphosphate glucose
(UDPGlc) and pyrophosphate
catalyzed by UDPGlc
pyrophosphorylase

7. Steps of Glycogenesis
Initial steps in glycogen synthesis
involve the protein glycogenin
which is glucosylated on a specific
tyrosine residue by UDPGlc
Glycogenin catalyzes the transfer
of a further 7 glucose residues from
UDPGlc in 14 linkage to form a
glycogen primer that is the
substrate for glycogen synthase

8. Steps of Glycogenesis
Glycogen synthase catalyzes
the formation of a glycosidic
bond between C-1 of the
glucose of UDPGlc & C-4 of a
terminal glucose residue of
glycogen primer, liberating UDP
So the branches of the
glycogen molecule become
elongated as successive 14
linkage are formed

9. Steps of Glycogenesis
When growing chain is at least
11 glucose residues long,
branching enzyme transfers a
part of the 14 chain (at least 6
glucose) to a neighboring chain
to form a 16 linkage
establishing a branch point
The branches grow by further
addition of 14 glucosyl units &
further branching

10. Pathway
of
Glycogenesis
Harper’s Biochemistry 31st edn p-165

11. Glycogenolysis
Substrate: Glycogen
Product: Glucose-1-phosphate [finally glucose in liver,
but in muscle G1P:free glucose = 10:1]
Site: Liver, Muscle, Brain
Comp: Cytoplasm
Nature: Catabolic
Rate limiting enzyme: Glycogen phosphorylase

12. Steps in Glycogenolysis
Glycogenolysis is not the reverse of
glycogenesis, it is a separate pathway
Glycogen phosphorylase catalyzes
the rate limiting step in glycogenolysis-
the phosphorolytic cleavage of the 14
linkages of glycogen to yield glucose-1-
phosphate. The enzyme requires
pyridoxal phosphate as it’s coenzyme

13. Steps in Glycogenolysis
The terminal glucosyl
residues are removed
sequentially until
approximately 4 residues
remain on either side of
16 branch

14. Steps in Glycogenolysis
The debranching enzyme has
2 catalytic sites
Glucan transferase: Transfers a
trisaccharide unit from one
branch to the other, exposing the
16 branch point
A 1,6-glycosidase: Catalyzes
hydrolysis of 16 glycoside bond
to liberate free glucose

15. Steps in Glycogenolysis
Further phosphorylase action
can then proceed
The combined action of
phosphorylase and debranching
enzyme leads to the complete
breakdown of glycogen

16. Steps in Glycogenolysis
Phosphoglucomutase
catalyzes the conversion of
glucose-1-phosphate to glucose-
6-phosphate
In liver (not muscle) glucose-6-
phosphatase catalyzes hydrolysis
of glucose-6-phosphate yielding
glucose

17. Pathway
of
Glycogenolysis
Harper’s Biochemistry 31st edn p-165

18. Regulation
Glycogen metabolism is
regulated by a balance in
activities between
glycogen synthase &
phosphorylase
Cyclic-AMP
simultaneously activate
phosphorylase & inhibit
glycogen synthase
Insulin
Glycogen
synthase
C-AMP
Glycogen
phosphorylase
Glucagon
Epinephrine

19. Regulation
cAMP is stimulated by
epinephrine & glucagon,
which in turn enhances
glycogenolysis
Whereas c-AMP is
inhibited by high
concentration of insulin
which in turn inhibits the
glycogenolysis
Insulin
Glycogen
synthase
c-AMP
Glycogen
phosphorylase
Glucagon
Epinephrine

20. Glycogen storage disease
Inherited deficiencies of enzymes of glycogen
metabolism in both liver & muscle cause glycogen
storage disease
Characterized by deficient mobilization of glycogen or
deposition of abnormal forms of glycogen
Leading to liver damage and muscle weakness; some
result in early death.