Glycogen is a key energy storage form of glucose, primarily stored in the liver and muscles, where it serves to maintain blood glucose levels and provide energy during physical activity. The synthesis (glycogenesis) and breakdown (glycogenolysis) of glycogen involve various enzymatic processes and are tightly regulated by hormones and cellular energy status. Glycogen storage diseases represent inherited disorders affecting glycogen metabolism, resulting in abnormal glycogen accumulation or mobilization.

1. GLYCOGEN METABOLISM
DEPARTMENT OF BIOCHEMISTRY
Prepared by:-
Supriya singh

2. GLYCOGEN- INTRODUCTION
Glycogen is a readily mobilized storage form of
glucose.
It is a very large, branched polymer of glucose
residues that can be broken down to yield glucose
molecules when energy is needed.
Most of the glucose residues in glycogen are
linked by α-1,4-glycosidic bonds.
Branches created by α-1,6-glycosidic bonds.

3. GLYCOGEN METABOLISM

4. GLYCOGEN STORAGE SITES
It is stored mainly in liver and muscle
The liver content of glycogen is greater than that
of muscle,
Since the muscle mass of the body is considerably
greater than that of the liver, about three-quarters
of total body glycogen is in muscle

5. Reasons for storing glycogen as a fuel
Glycogen serves as a buffer to maintain blood-
glucose levels.
Glucose is virtually the only fuel used by the
brain, except during prolonged starvation.
The glucose from glycogen is readily mobilized
and is therefore a good source of energy for
sudden, strenuous activity.
Unlike fatty acids, the released glucose can
provide energy in the absence of oxygen and can
thus supply energy for anaerobic activity.

6. GLYCOGENESIS
 Glycogenesis is the synthesis of glycogen from
glucose.
 Glycogenesis mainly occurs in muscle and liver.
Takes place in cytosol and require ATP and UTP.
 Liver glycogen functions to store and export
glucose to maintain blood glucose between meals.

7. STEPS OF GLYCOGENESIS
A. Synthesis of UDP-glucose
B. Synthesis of a primer to initiate glycogen synthesis
C. Elongation of chain by glycogen synthase
D. Formation of branches

8. A. Synthesis of UDP-glucose
 Glucose-1-phosphate reacts with uridine tri-
phosphate (UTP) to form uridine diphosphate
glucose (UDPG)
 This reaction is catalysed by UDPG pyro-
phosphorylase
Glucose-1-phosphate + UTP UDP-glucose + PPi
UDP-glucose
pyrophosphorylase

9. B. Synthesis of a primer to initiate
glycogen synthesis
 Glucose moiety from UDP-glucose is transferred to a
glycogen primer (Glycogenin) molecule.
 Primer is made up of protein-carbohydrate complex.
 It a dimeric protein, having two identical monomers to which
an oligosaccharide chain of 7 glucose units is added.
 UDP is released and glucose is added to the glycogen primer
 Glycogen primer having n glucose units would have n+1
glucose units after the reaction

10. B. Synthesis of a primer to initiate
glycogen synthesis
 Carbon 1 of the new glucose unit forms a
glycosidic bond with carbon 4 of the last glucose
unit
 The reaction is catalysedby glycogen synthase
Glycogen primer(n) + UDP-glucose Glycogen (n+1) + UDP
Glycogen synthase

11. C. Elongation of chain by glycogen
synthase
 Glycogen synthase responsible for formation of
1,4-glycosidic linkages.
 This enzyme transfers the glucose from UDP-
glucose to the non-reducing end of glycogen to
from α-1,4 linkages.

12. D. Formation of branches
Addition of glucose units to the glycogen primer continues until
the chain contains about eleven glucose units
Then, amylo-1,4 1,6-transglucosidase detaches a fragment of
6-7 glucose units from the growing end
The two branches start growing again by addition of glucose
units by α-1,4-glycosidic bonds catalysed by glycogen synthase
When the branches contain about 11 glucose units, branching
enzyme acts again and creates more branches
The process of lengthening and branching continues until a large
and highly branched glycogen molecule is formed

13. The overall reaction of the glycogen synthesis for the
reaction of each residue is
(Glucose)n + Glucose + 2ATP (Glucose)n+1 + 2ATP + Pi

14. GLYCOGEN SYNTHESIS

15. The regulatory enzyme is glycogen synthase
which is regulated by covalent modification
is addition orThe covalent modification
removal of phosphate
The enzyme exists in two forms – glycogen
synthase a and glycogen synthase b
The covalent modification
removal of phosphate
REGULATION

16.  Glycogen synthase a is the dephosphorylated
and active form of the enzyme
 Glycogen synthase b is the phosphorylated
and inactive form
 Addition of phosphate converts glycogen
synthase a into glycogen synthase b
 Removal of phosphate converts glycogen
synthase b into glycogen synthase a

17.  Phosphate is added to glycogen synthase a by
protein kinase A
 Phosphate is removed from glycogen synthase b
by protein phosphatase-1
 Protein kinase A and protein phosphatase- 1 are
regulated by cAMP

18.  Intracellular concentration Of cAMP is regulated by
some hormones
 So, the ultimate regulators of glycogenesis are epinephrine,
glucagon and insulin
 Epinephrine and glucagon increase the concentration of cAMP
 Insulin decreases the concentration of cAMP

19.  cAMP is the regulatorof protein kinase A
(cAMP-dependent protein kinase)
 Protein kinase A is a tetramer made up of
two regulatory (R) and two catalytic (C)
subunits

20. GLYCOGENOLYSIS (DEGRADATION
OF GLYCOGEN)
 Glycogen is degraded by breaking α-1,4- and α-1,6-
glycosidic bonds
Glycogen degradation consists of three steps:
(1) Action of glycogen phosphorylase.
(2) Action of debranching enzyme.
(3) Formation of glucose-6-phosphate and glucose.

21. 1.Action of glycogen phosphorylase
 The α-1,4-glycosidic bonds are cleaved by glycogen
phosphorylase to yield glucose-1-phosphate.
 Called phosphorolysis- continues until four glucose
residues remain on either side of branching pont.
 The glycogen formed known as Limit dextrin which
cannot further degraded.

22. 2.Action of debranching enzyme
 The branches of glycogen cleaved by two enzyme c/d
debranching enzyme, hence it is a bifunctional enzyme.
 Glycosyl 4:4 transferase removes a fragment of three or
four glucose residues.
 Amylo α-1,6-glucosidase breaks the α-1,6 bond at a
branch and releases a free glucose.

23. 3. Formation of glucose-6-phosphate
and glucose.
 Glycogen phosphorylase and debranching enzyme,
glucose 1-phosphate and free glucose are produced.
 Glucose 1-phosphate is converted to glucose 6-
phosphate by the enzyme phosphoglucomutase.
 Glucose6-phosphatase cleaves glucose 6-phosphate to
glucose.

25. CONVERSION OF GLUCOSE-6-P TO FREE
GLUCOSE
The liver contains a hydrolytic enzyme, glucose 6-
phosphatase, which cleaves the phosphoryl group to form
free glucose and orthophosphate.
Glucose 6-phosphatase is absent in muscles.
Consequently, glucose 6-phosphate is retained for the
generation of ATP.
The liver releases glucose into the blood during muscular
activity and between meals to be taken up primarily by the
brain and skeletal muscle.

26. REGULATION OF GLYCOGEN METABOLISM
The principal enzymes controlling glycogen
metabolism—glycogen phosphorylase and glycogen
synthase—are regulated by three mechanisms
1. Allosteric regulation
2. Hormonal regulation
3. Influence of calcium

27. 1. ALLOSTERIC REGULATION
Glycogen synthesis increase when substrate
availability and energy (ATP) levels high.
Glycogen breakdown increase when glucose conc.
and energy level low
In well-fed state glucose-6-phosphate availability
high which activates glycogen synthase and inhibits
glycogen phosphorylase.
Also free glucose and ATP inhibits glycogen
phosphorylase.

28. 2. HORMONAL REGULATION
Hormones bring covalent modification, phosphorylation
and dephosphorylation of enzyme proteins, thus control
glycogen synthesis and degradation.
Hormones epinephrine and nor-epinephrine, and
glucagon activate adenylate cyclase and increase
production of cAMP.
Enzyme phosphodiesterase breaks down cAMP.
Hormone insulin increase phosphodiesterase activity in
liver

29. CLINICAL SIGNIFICANCE
Glycogen storage diseases
"Glycogen storage disease" is a generic term to
describe a group of inherited disorders
characterized by deposition of an abnormal type or
quantity of glycogen in tissues, or failure to mobilize
glycogen.

30. Tarui’s disease

32. QUESTIONS
Q1. What is Glycogenesis? Describe briefly the
metabolic pathway involved in glycogenesis.
Q2. Describe the regulation of glycogenesis,
glycogenolysis?
Q3. Short Notes on-
a) Glycogen storage disease
b) Glycogenesis
c) Glycogenolysis