GLYCOGENESIS

Dr Nazakat Hussain
 WHAT IS GLYCOGEN?
• Glycogen is the storage form of glucose, only store in two
organs: in the liver (app.150 g) and in skeletal muscles
(app.300 g).
• It is mobilized as glucose whenever body tissues require.
• It is the only immediately available reserve store of blood
glucose.
• A high liver glycogen level protects the liver cells against
the harmful effects of many poisons and chemicals, e.g.
CCl4, ethyl alcohol, arsenic, various bacterial toxins.
• After 12 to 18 hours of fasting, the liver becomes almost
totally depleted of glycogen.
 BIOMEDICAL IMPORTANCE OF
GLYCOGEN
• Liver glycogen is largely concerned with storage and
supply of glucose-1-P, which is converted to glucose, for
maintenance of blood glucose, particularly in between
meals.
• Muscle glycogen on the other hand, is to act as readily
available source of intermediates of glycolysis for
provision of energy within the muscle itself. Muscle
glycogen cannot directly contribute to blood glucose level.
• Inherited deficiency of enzymes in the pathway of
glycogen metabolism produces certain inherited disorders
called as Glycogen storage diseases (GSDs)
STRUCTURE OF GLYCOGEN
• Glycogen is a strongly branched polymer of
α-D-glucose, with glucose residues in the
linear chains linked by 1→4-bonds (~93% of
the total number of bonds) and with
branching after every 4-8 residues formed
by 1→6-glycosidic bonds (~7% of the total
number of bonds).
• Chemical formula for glycogen (C6H10O5)n
 WHAT IS THE PROCESS OF
GLYCOGENESIS?
• Glycogenesis, the formation of glycogen, the primary
carbohydrate stored in the liver and muscle cells of
animals, from glucose.
• Glycogenesis takes place when blood glucose levels
are sufficiently high to allow excess glucose to be
stored in liver and muscle cells.
• The primary purpose of glycogenesis is to make sure
the body does not run out of glucose. Glucose is
important as it is the body's primary source of
energy. Without an adequate supply of glucose in
the body, vital organs will eventually shut down
 STEPS OF GLYCOGENESIS
• Glucose is converted into GLUCOSE 6-PHOSPHATE by the
action of glucokinase or hexokinase with conversion of
ATP to ADP.
• Glucose-6-phosphate is converted into glucose-1-
phosphate by the action of PHOSPHOGLUCOMUTASE,
passing through the obligatory intermediate glucose-1,6-
bisphosphate.
• Glucose-1-phosphate is converted into UDP-glucose by
the action of the enzyme UDP-GLUCOSE
PYROPHOSPHORYLASE. Pyrophosphate is formed, which
is later hydrolysed by pyrophosphatase into two
phosphate molecules.
STEPS OF GLYCOGENESIS
• The enzyme GLYCOGENIN is needed to create
initial short glycogen chains, which are then
lengthened and branched by the other enzymes
of glycogenesis
• Glycogenin, a homodimer, has a tyrosine
residue on each subunit that serves as the
anchor for the reducing end of glycogen.
Initially, about seven UDP-glucose molecules
are added to each tyrosine residue by
glycogenin, forming α(1→4) bonds.
 STEPS OF GLYCOGENESIS
• Once a chain of seven glucose monomers is formed,
glycogen synthase binds to the growing glycogen chain
and adds UDP-glucose to the 4-hydroxyl group of the
glucosyl residue on the non-reducing end of the glycogen
chain, forming more α(1→4) bonds in the process.
• Branches are made by glycogen branching enzyme
(known as amylo α(1:4)→α(1:6)transglycosylase), which
transfers the end of the chain onto an earlier part via α-
1:6 glycosidic bond, forming branches, which further
grow by addition of more α-1:4 glycosidic units.
STIMULATION OF GLYCOGENESIS
1. INSULIN:
• Insulin increases the Protein-phosphatase-1 activity
2. GLUCOCORTICOIDS:
• Effects seen 2 to 3 hours after administration
• Enhances gluconeogenesis and glycogen synthesis in liver
• Increases activity of Protein phosphatase-1, and
• Increases synthesis of the enzyme glycogen synthase
3. GLUCOSE:
• High substrate concentration increases synthesis (allostery)
INHIBITION OF GLYCOGENESIS
1. Increased concentration of glycogen inhibits
glycogenesis, “Feedback” inhibition
2. Increased concentration of cyclic-AMP ↑
stimulates inhibitor-1, to form ‘active’ inhibitor-1-P
which in turn inhibits Protein Phosphatase-1
REGULATION OF
GLYCOGENESIS
 EPINEPHRINE
• Epinephrine, also called adrenaline, is the
hormone released in the fight-or-flight response
or when your body is frightened or stressed.
Epinephrine negatively regulates glycogenesis, by
disrupting the proteins necessary for the process.
• During a flight-or-fight response, the body wants
all the available energy ready for disposal by the
cells. Thus, it stops glycogenesis,
 INSULIN
• When the body receives a large meal and
the blood glucose levels are up, the
pancreas releases insulin, a hormone which
tells the cells to uptake and store glucose.
• This stimulates the process of glycogenesis,.
Lots of glycogen is stored in the liver,