Glycogen synthesis is a basic process to store extra glucose and it is one of the most important process occuring in the body

1. Glycogen
Humans consume 160 g of glucose per day
75% of that is in the brain
Body fluids contain only 20 g of glucose
Glycogen stores yield 180-200 g of glucose
So the body must be able to make its own
glucose

2. In the well-fed state the glucose after absorption is
taken by liver and deposited as a glycogen
Glycogen is a very large, branched polymer of glucose
residues that can be broken down to yields glucose
molecules when energy is needed
GLYCOGEN SYNTHESIS

3. Liver (10 % of weight) and
skeletal muscles (2 %)
– two major sites of
glycogen storage
Glycogen is stored in
cytosolic granules in
muscle and liver cells of
vertebrates
Glycogen serves as a buffer to maintain blood-glucose
level.
Stable blood glucose level is especially important for
brain where it is the only fuel.
The glucose from glycogen is readily mobilized and is
therefore a good source of energy for sudden, strenuous
activity.

5. Variation of liver glycogen levels
between meals and during the
nocturnal fast.

7. Most glucose residues in glycogen are linked by a-1,4-
glyco-sidic bonds, branches are created by a-1,6-
glycosidic bonds

8. Glycogen Synthesis
• Synthesis and degradation of
glycogen require separate
enzymatic steps
• Cellular glucose converted to
G6P by hexokinase
• Three separate enzymatic steps
are required to incorporate one
G6P into glycogen
• Glycogen synthase is the
major regulatory step

9. • Phosphoglucomutase catalyzes the conversion of glucose 6-
phosphate (G6P) to glucose 1-phosphate (G1P).
Glucose 1-Phosphate formation

10. Synthesis of glycogen (glycogenesis)
- Glycogen is synthesized from molecules of α-D-glucose.
The process occurs in cytosol, and requires energy
supplied by ATP (for phosphorylation of glucose) & uridine
triphosphate (UTP).
A. Synthesis of UDP-glucose
B. Synthesis of a primer to initiate glycogen synthesis
C. Elongation of glycogen chain
D. Formation of branches in glycogen

11. Synthesis of glycogen (glycogenesis)
A. Synthesis of UDP-glucose
- α-D-glucose attached to UDP is the source of all of
glucosyl residues that are added to the growing glycogen
molecule
- UDP-glucose is synthesized from glucose-1-P & UTP by
UDP-glucose pyrophosphorylase
- The high-energy bond in pyrophosphate (PPi), the 2nd
product of the reaction, is hydrolyzed to 2 inorganic
phosphates (Pi) by pyrophosphatase, which ensures that
synthesis of UDP-gluc proceeds in direction of UDP-gluc
production
Note: G-6-P is converted to G-1-P by phosphoglucomutase.
G-1,6-BP is an obligatory intermediate in this reaction

12. Figure 11.4. The structure of UDP-glucose.

13. UDP-glucose is activated form of
glucose.
UDP-glucose is synthesized from
glucose-1-phosphate and
uridine triphosphate (UTP) in a
reaction catalized by UDP-
glucose pyrophosphorylase

14. Glycogen synthase adds glucose
to the nonreducing end of
glycogen

15. - Glycogen synthase is responsible for making α (1→4)
linkages in glycogen. This enzyme can’t initiate chain
synthesis using free gluc as an acceptor of a molecule of
glucose from UDP- glucose. Instead, it can only elongate
already existing chains of glucose.
- Therefore, a fragment of glycogen can serve as a primer in
cells whose glycogen stores are not totally depleted
- In the absence of a glycogen fragment, a protein, called
glycogenin, can serve as an acceptor of glucose residues
B. Synthesis of a primer to initiate glycogen
synthesis

16. - Side chain hydroxyl group of a specific Tyrosine serves
as the site at which the initial glucose unit is attached
- Transfer of first few molecules of glucose from UDP-
glucose to glycogenin is catalyzed by glycogenin itself,
which can then transfer additional glucosyl units to the
growing α (1→4)-linked glucosyl chain
- This short chain serves as an acceptor of future glucose
residues
Note: glycogenin stays associated with & is found in
center of completed glycogen molecule
B. Synthesis of a primer to initiate glycogen
synthesis

17. Glycogenin initiates glycogen synthesis.
Glycogenin is an enzyme that catalyzes attachment of a
glucose molecule to one of its own tyrosine residues.
Glycogenin is a dimer, and evidence indicates that the 2
copies of the enzyme glucosylate one another.
Tyr active site
active site Tyr
Glycogenin dimer

18. A glycosidic bond is formed between the anomeric C1 of the
glucose moiety derived from UDP-glucose and the hydroxyl
oxygen of a tyrosine side-chain of Glycogenin.
UDP is released as a product.
H O
OH
H
OH
H
OH
CH2OH
H
O H
H
OH
H
OH
CH2OH
H
O
H
H
C
CH
NH
C
H2
O
O
H O
OH
H
OH
H
OH
CH2OH
H
H
C
CH
NH
C
H2
O
O
1
5
4
3 2
6
H O
OH
H
OH
H
OH
CH2OH
H
H
O
1
5
4
3 2
6
P O P O Uridine
O
O
O
O
C
CH
NH
C
H2
HO
O
tyrosine residue
of Glycogenin
O-linked
glucose
residue
+ UDP
UDP-glucose

19. Glycogenin then catalyzes glucosylation at C4 of the attached
glucose (UDP-glucose again the donor), to yield an O-linked
disaccharide with α(1-4) glycosidic linkage.
This is repeated until a short linear glucose polymer with
α(1-4) glycosidic linkages is built up on Glycogenin.
H O
OH
H
OH
H
OH
CH2OH
H
O H
H
OH
H
OH
CH2OH
H
O
H
H
C
CH
NH
C
H2
O
O
H O
OH
H
OH
H
OH
CH2OH
H
H
C
CH
NH
C
H2
O
O
1
5
4
3 2
6
UDP-glucose
O-linked
glucose
residue
(14)
linkage
+ UDP
+ UDP

20. C. Elongation of glycogen chain by glycogen
synthase
-
Elongation of glycogen chain involves transfer of glucose
from UDP-glucose to the non-reducing end of growing
chain, forming a new glycosidic bond b/w the anomeric
hydroxyl of C-1 of activated glucose & C-4 of accepting
glucosyl residue
Note: “non-reducing end” of a CHO chain is one in which
anomeric C of terminal sugar is linked by a glycosidic
bond, making terminal sugar “non-reducing”.
- The enzyme responsible for making α (1→4) linkages in
glycogen is glycogen synthase
Note: UDP released when the new α (1→4) glycosidic bond
is made can be converted back to UTP by nucleoside
diphosphate kinase (UDP + ATP ↔ UTP + ADP)

21. D. Formation of branches in glycogen
- If no other synthetic enz’s acted on the chain, resulting
structure would be a linear molecule of glucosyl residues
attached by α (1→4) linkages.
- One of the enyzme is found in plant tissues called
amylose. In contrast, glycogen has branches located, on
av., 8 glucosyl residues apart, resulting in a highly
branched, tree-like structure that is far more soluble than
unbranched amylose
- Branching also increases the No. of non-reducing ends to
which new glucosyl residues can be added (and also, from
which these residues can be removed), thereby greatly
accelerating the rate at which glycogen synthesis &
degradation can occur, & dramatically increasing the size
of the molecule

22. 1. Synthesis of branches:
- Branches are made by action of “branching enzyme”,
amylose-α (1→4) → α (1→6)-transglucosidase. This enz
transfers a chain of 5 to 8 glucosyl residues from non-
reducing end of glycogen chain [breaking α (1→4) bond]
to another residue on the chain and attaches it by an α
(1→6) linkage
- Resulting new, non-reducing end, as well as the old non-
reducing end from which the 5 to 8 residues were
removed, can now be elongated by glycogen synthase
2. Synthesis of additional branches:
- After elongation of these two ends has been accomplished
by glycogen synthase, their terminal 5 to 8 glucosyl
residues can be removed & used to make further
branches

23. A branching enzyme forms -1,6-linkages
Glycogen synthase
catalyzes only -1,4-linkages.
The branching enzyme is
required to form -1,6-
linkages.
Branching is important
because it increases the
solubility of glycogen.
Branching creates a large
number of terminal residues,
the sites of action of glycogen
phosphorylase and synthase.

24. Figure 11.5. Glycogen synthesis.