By Anagha A Central university of Kerala

1. ANAGHA.A
BZY051904

2. GLYCOGEN
 Main structural polysaccharide of animal cells.
 A polymer of α-1,4 linked glucose subunits with α-1,6
linked branches
 Abundant in liver and skeletal muscle.
 Represents 10% of the weight of liver and 1-2% of the
weight of the muscle.

3. STRUCTURE OF GLYCOGEN

4. GLYCOGENOLYSIS
 Process by which Glycogen is broken down into
Glucose-6-phosphate to provide immediate
energy
 It occurs in cell cytosol in the liver and muscles
and is stimulated by hormones Glucagon and
Epinephrine
 It is accomplished by 2 principle processes,
namely Phosphorolysis and Hydrolysis

5. IMPORTANT STEPS INVOLVED:
 Cleavage of α-1,4 Glycosidic linkage by the
enzyme Glycogen phosphorylase
 Cleavage of α-1,6 Glycosidic linkage (branches)
by Glycogen debranching enzyme
 Conversion of Glucose-1-phosphate to Glucose-
6-phosphate by the enzyme
Phosphoglucomutase

6. 1. Cleavage of α-1,4 glycosidic linkage
by Glycogen phosphorylase:
 Glycogen phosphorylase cleaves the Glycogen
by the addition of an Orthophosphate to yield
Glucose-1-phosphate
 The cleavage of a bond by the addition of an
orthophosphate is called Phosphorolysis
 Glycogen + Pᵢ glucose-1-phosphate + glycogen
(n residues) (n-1 residues)

7.  Phosphorylase catalyses the sequential removal
of glucosyl residues from the nonreducing ends
of the glycogen molecule (the ends with a free
OH group on C-4).
 Orthophosphate splits the glycosidic linkage
between C-1 of the terminal residue and C-4 of
the adjacent one.
 However, for the enzyme to perform, a coenzyme
which is a derivative of Vitamin B₆ called
Pyridoxal phosphate (PLP) comes into action.

8. Reaction Involved:

10. Mechanism: Pyridoxal phosphate
participates in the phosphorolytic cleavage
 The aldehyde group of PLP forms a Schiff’s base linkage
with a specific lysine side chain of the enzyme.
 The reacting orthophosphate takes a position between the
5’ phosphate group of PLP.
 Orthophosphate (in the form of HPO₄²‾) donate a proton
to the Oxygen atom attached to C-4 of the departing
glycogen chain and simultaneously acquires a proton
from PLP.

11.  Carbocation intermediate formed is attacked by
Orthophosphate to form α-glucose-1-phosphate , with
the return of hydrogen atom to PLP.

12. Reaction Involved:

13. 2. Cleavage of α-1,6 glycosidic linkage
by Glycogen debranching enzyme:
 Phosphorylase enzyme cannot cleave the branches of
glycogen.
 It stops cleaving α-1,6 linkages when it reaches terminal
4 residues away from branch point.
 2 additional enzymes, transferase and α-1,6-
glucosidase remodel glycogen for continued cleavage
by phosphorylase

14. Role of transferase and α-1,6-glucosidase
 Transferase
Transfers 3 glucosyl residues from one outer branch to
another.
 α-1,6-glucosidase
Hydrolyses the α-1,6-glycosidic linkages present in the
branches which releases a free glucose molecule which in
turn gets phosphorylated by the glycolytic enzyme
hexokinase.

15. Reaction Involved:

17. 3. Conversion of glucose-1-phosphate to
glucose-6-phosphate by
phosphoglucomutase
 Glucose-1-phosphate formed in the phosphorolytic
cleavage is converted to glucose-6-phosphate by the
enzyme phosphoglucomutase
 The mutase enzyme has a phosphorylated serine residue
which transfers phosphoryl group to C-6 OH group of
glucose-1-phosphate to form glucose-1,6-biphosphate.
 The C-1 phosphoryl group of this intermediate is
shuttled to same serine residue resulting in the
formation of glucose-6-phosphate and regeneration of
the phosphoenzyme.

18.  The glucose-6-phosphate can either enter the glycolytic
pathway or is directly released into the blood.

19. Liver Glycogenolysis

20. Muscle Glycogenolysis

21. Biological Significance:
 When the blood glucose is low, Glucose-6-phosphatase
(found in the lumen of ER of liver cells) acts on glucose-
6-phosphate and forms glucose which restores the blood
glucose level.
 Stored glycogen serves as a fuel reserve for following
reasons:
1. Glycogen can be readily metabolized
2. Glycogen can generate energy in the absence of O₂
3. Brain depends on continuous glucose supply.

22. Reference:
 Lubert Stryer with Gregory J & Gatto Jr. ,
BIOCHEMISTRY, 7th Edition
 David L Nelson and M.Cox , Lehninger, PRINCIPLES
OF BIOCHEMISTRY, 6th Edition
 Donald Voet & Judith G Voet, BIOCHEMISTRY, 5th
Edition