Metabolisme

Glikogenesis & Glukogenolisis

Prof. Dr. Suhartati, dr., MS

 Definisi GLIKOGENESIS
• Pembentukan glikogen dari glukosa

• Tempat di sitosol dalam bentuk granula

terutama di liver (6%) dan di otot (1%).

• Glikogen Liver
= 1800 g X 4%= 72 g
Glikogen otot
= 35000 X 0.7%
= 245 g
Glycogen is a polymer of glucose
residues linked by
  (1→4) glycosidic bonds, mainly
  (1→6) glycosidic bonds, at
branch points : at about every 8-
10th residue
 Diagram Glikogenesis

Glucosa dirubah menjadi glucosa 6P

menggunakan 1 ATP

Glukosa-6P dirubah menjadi glucose-1P, (UDPG pirofosforilase)

dengan mengaktivkan UTP membentuk
UTP glucosa

UTP-glucose menangkap akhir rantai

glikogen, UDP di lepas (dan merubah (Fosfoglukomutase)
UTP oleh ATP)
 1) Formation of Glucose-6-Phosphate

Glucose is converted to glucose-6-phosphate, using

ATP, in the first step of glycolysis

P O CH2
O
OH
OH OH
OH
Glucose-6-phosphate
 2) Formation of Glucose-1-Phosphate
Glucose-6-phosphate is converted
to glucose-1-phosphate

P O CH2 H O CH2
O O
OH OH
OH OH OH O P
OH (Fosfoglukomutase) OH

Glucose-6-phosphate Glucose-1-phosphate
 3) Formation of UTP-Glucose

UTP activates glucose-1-phosphate to form

UDP-glucose and pyrophosphate (PPi)

(UDPG pirofosforilase)

O
CH2OH
H
O N
OH O O
O N
OH O P O P O CH2
O
OH O- O- Glucose is first activated to uridine
diphosphate glucose (UDP-G).
OH OH

UDP-glucose is transferred to the

UDP-glucose hydroxyl group of an existing primer
(called glycogenin), forming an α-[14]
glycosidic link.
 O

CH2OH HN

H O H
H O N
OH H O O

OH O P O P O CH2
O
H OH O O H H
H H
OH OH

UDPG
Structure of UDP-Glucose
Branching enzyme
 Glycogen Formation

The glucose in UDP-glucose adds to glycogen

UDP-Glucose + glycogen  glycogen-glucose + UDP

UDP-glucose is transferred to the hydroxyl group of an existing primer

(called glycogenin), forming an α-[14] glycosidic link.
• The process is repeated till the chain length
reaches at least 11 glucose units linked by
- [1 4] linkage.

• a branching enzyme ( α 1,6 transglukosidase)

about 7 glucose units to a neighboring chain,
thus establishing a new - [1 6] branch
point.

• The branches grow by further addition of

[14] glycosyl units and further branching.
Effects of GSK3 on
glycogen synthase
activity
GSK3 : glycogen synthase kinase
CKII : Casein Kinase 2
PPI : fosfoprotein fosfatasa-1.
Pengendalian Glikogen sintase di otot
Pengendalian glikogenesis & glikogenolisis
Glycogen synthesis and breakdown are reciprocally regulated

Red=inactive forms, green = active forms.

Active Inactive

Protein phosphatase 1 (PP1) regulates

glycogen metabolism.
Regulation of carbohydrate metabolism in the hepatocyte
 Glycogenolysis

Glycogenolysis is the breakdown of glycogen to glucose (Glycogen phosphorylase is an

exoglucosidase)

The glucose is phosphorylated as it is cleaved from the glycogen to form glucose-1-

phosphate

Glucose-1-phosphate can be converted to glucose-6-phosphate, which can enter

glycolysis

Phosphorylated glucose can’t be absorbed into cells

- in the liver and kidneys, glucose-6-phosphate can be hydrolized to glucose

Glycogenolysis is activated by glucogon in the liver and epinephrine in muscles

- these are produced when blood glucose levels are low

Glycogenolysis is inhibited by insulin

- insulin is produced when blood glucose levels are high
 Glycogen catabolism (glycogenolysis)

Pi Gn-1 H2O Pi
Gn G-1-P G-6-P G
Phosphorylase G-6-Pase

Phosphorylase: It is an exoglucosidase
The end products: 85% of G-1-P and 15%
of free G;
There is no the activity of glucose 6-
phosphatase (G-6-Pase) in skeletal
muscle.
 Glycogen phosphorylase

Transferase activity of debranching enzyme

(1→6) glucosidase activity of debranching enzyme

Debranching enzyme:

glucan transferase
-1,6-glucosidase
Glucose-6-phosphate is dephosphorylated
in the liver for transport out of the liver
 Control of Glycogen Breakdown
• Glucogon/Epinephrine signaling pathway
– Starts phosphorylation cascade vis cAMP
– activates glycogen phosphorylase
• Glycogen phosphorylase cleaves glucose residues
off glycogen, generating glucose-1-phosphate
 Regulation phosphorylase
Regulation of glycogen metabolism is different in
muscle and liver.
• In muscle, the end served by glycolysis is ATP
production and the rate of glycolysis increases as
muscle works more, demanding more ATP.
• The liver has a different role in whole-body
metabolism and glucose metabolism in the liver is
different. The liver makes sure that glucose level
is constant in the blood, producing and exporting
Glc.
Difference in the regulation of carbohydrate metabolism in liver and muscle
Regulation of carbohydrate synthesis
in the heptocyte
Allosteric and Phosphorylation Regulation -
Glycogen Phosphorylase
Covalent modification

Glucagon Adenylyl
epinephrine receptor G protein cyclase

cAMP PKA Phosphorylase

Glycogen synthase

glycogenolysis
Blood sugar
glycogenesis
Glycogenolysis: The
biochemical pathway for
breakdown of glycogen
to free glucose.

Glycogenolysis occurs
in muscle cells when
there is an immediate
need for energy.

Glycogenolysis occurs
in the liver when blood
glucose is low.
Overview of Glycogen Synthesis and Breakdown
GLYCOGENESIS & GLYCOGENOLYSIS
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 two copies of the enzyme glucosylate one
another.
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.