Quarter 4_Grade 8_Digestive System Structure and Functions
Glycogen synthesis.ppt
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.
4.
5. Variation of liver glycogen levels
between meals and during the
nocturnal fast.
6.
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
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
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
(14)
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.