Glycogen Metabolism.

GLYCOGEN METABOLISM
• Glucose is stored as Glycogen in animals & as starch in plants.
• It is stored in liver and muscle, Due to more muscle mass, the quantity of
glycogen in muscle (250 g) is about three times higher than that in the liver (75
g).
• Most of the glycogen metabolism enzymes present in cytoplasm.
• Glycogen metabolism - Glycogenesis (glycogen synthesis), Glycogenolysis

(Breakdown of glycogen).
FUNCTIONS OF GLYCOGEN
• Major function of liver glycogen is to provide glucose during fasting state.
• Glycogen content of liver (10 g/100 g tissue) is more than in the skeletal muscle
(1-2 g/100 g), but the total quantity of muscle glycogen is more than liver
glycogen because of larger muscle mass.
• Liver glycogen stores increase in a well-fed state which are depleted during
fasting.
• Muscle glycogen serves as a fuel reserve for the supply of ATP during muscle
contraction.
GLYCOGENESIS
• Synthesis of glycogen from glucose called glycogenesis
• It requires ATP and UTP besides glucose and reaction takes place in cytosol
1. Synthesis of UDP-glucose
• The enzymes hexokinase (in muscle) and glucokinase (in liver) convert glucose
to glucose 6-phosphate
• Phosphoglucomutase catalyses the conversion of glucose 6-phosphate to

glucose 1-phosphate.
• Uridine diphosphate glucose (UDPG) is synthesized from glucose 1-
phosphate and UTP by UDP-glucose pyrophosphorylase
2. Requirement of primer to initiate glycogenesis
• pre excisting glycogen must act as a ‘primer’ to initiate glycogen synthesis.
• It is recently found that in absence of glycogen primer, a specific Protein namely

‘glycogenin’ (which can act as both enzyme & substrate)can accept glucose from UDPG.
• The hydroxyl group of the amino acid tyrosine of glycogenin is the site at which the
initial glucose unit is attached
• Enzyme glycogen initiator synthase transfers the first molecule of glucose to glycogenin
• Glycogenin itself takes up a few glucose residues to form a fragment of primer which
serves as an acceptor for the rest of the glucose molecules
3. Glycogen synthesis by glycogen synthase
• Glycogen synthase is responsible for the formation of 1,4-glycosidic linkages.
• This enzyme transfers the glucose from UDP-glucose to the non-reducing end of
glycogen to form α-1,4 linkages.
4. Formation of branches in glycogen
• Glycogen synthase can catalyse the synthesis of a linear unbranched molecule with
1,4 α -glycosidic linkages
• The formation of branches is brought about by the action of a branching enzyme,

namely glucosyl α 1-6 transferase.
• This enzyme transfers a small fragment of five to eight glucose residues from the
non-reducing end of glycogen chain (by breaking α -1,4 linkages) to another
glucose residue where it is linked by α-1,6 bond.
• This leads to the formation of a new non-reducing end, besides the existing one.
• Glycogen is further elongated and branched, respectively by the enzymes glycogen

synthase and glucosy α -l,6 transferase.
Overall reactions
GLYCOGENOLYSIS
• Breakdown/degradation of stored glycogen in liver and muscle constitutes for

glycogenolysis.
• Enzymes – present in cytosol.
• Glycogen is degraded by breakdown of α-1,4 and α-1,6 linkage.

1. Action of glycogen phosphorylase
• The α-1,4-glycosidic bonds are cleaved sequentially by the enzyme glycogen

phosphorylase to yield glucose 1-phosphate, this process is called phosphorolysis.
• Pyridoxal phosphate (PLP- vitamin B6) used as co-enzyme for glycogen

phosphorylase.
• This process will continues until four glucose residues remain on either side of
branching point (α -1,6-glycosidic link)
• The glycogen so formed is known as limit dextrin which cannot be further degraded
by phosphorylase.
2. Action of debranching enzyme
• Branches of glycogen are cleaved by two enzyme activities present on a single

polypeptide called debranching enzyme, it is an bifunctional enzyme.
• Glycosyl 4 : 4 transferase activity removes a fragment of three or four glucose

residues attached at a branch and transfers them to another chain.
• Amylo α -1,6-glucosidase breaks the α -1,6 bond at the branch with a
single glucose residue and releases a free glucose.
• The remaining molecule of glycogen is again available for the action of

phosphorylase and debranching enzyme to repeat the reactions.
3. Formation of glucose 6-phosphate and glucose
• By the help of Glycogen phosphorylase and de-branching enzyme glucose 1-

phosphate and free glucose in a ratio of 8 : 1 are produced.
• The fate of glucose 6-phosphate depends on the tissue.
• The liver, kidney and intestine contain the enzyme glucose 6-phosphatase that cleaves
glucose 6-phosphate to glucose.
• This enzyme is absent in muscle and brain, hence free glucose cannot be produced from
glucose 6-phosphate in these tissues.
• Therefore, liver is the major glycogen storage organ to provide glucose into the circulation to
be utilised by various tissues.
• In the peripheral tissues, glucose 6-phosphate produced by glycogenolysis will be used for
glycolysis.
• Glucose 6-phosphatase is absent in muscle, some amount of free glucose (8-10% of

glycogen) is produced in glycogenolysis due to the action of debranching enzyme.
REGULATION
• Key enzymes- Glycogen synthase, glycogen phosphorylase
• Hormones- Insulin and glucagon/epinephrine
• Glycogen synthase active in dephosphorylated state.
• Glycogen phosphorylase active in phosphorylated state.
• Insulin favours glucose utilization and decrease glucose level.
• Glucagon favours glucose formation.

GLYCOGEN STORAGE DISEASES
• Metabolic defects concerned with glycogen sysnthesis and degradation are

collectively referred as the glycogen storage diseases.
Glycogen Storage Disease Type-I
• It is also called Von Gierke’s Disease. Most common type of glycogen storage
disease is type I.
• Incidence is 1 in 100,000 live births.
• Glucose-6-phosphatase is deficient.
• Glycogen gets deposited in liver. Massive liver enlargement may lead to cirrhosis.
Symptoms, in addition to
Glycogen Storage Disease
glycogen accumulation
Type I, liver deficiency of hypoglycemia (low blood
Glucose-6-phosphatase (von glucose) when fasting, liver
Gierke's disease) enlargement.
Type II deficiency of lysosomal Death occurs at an early age
α-1,4 glucosidase (Pompe’s due to heart failure
disease)
Type III, deficiency of Similar to type I but milder
debranching enzyme (Cori’s
disease)
Type IV, deficiency of branching liver dysfunction and early
enzyme in various organs, death.
including liver (Andersen's
disease)
Symptoms, in addition to
Glycogen Storage Disease
glycogen accumulation
Type V, muscle deficiency of muscle cramps with exercise.
Glycogen Phosphorylase
(McArdle's disease)
Type VI, deficiency of liver Liver enlarged; mild
glycogen phosphorylase (Her’s hypoglycemia and ketosis
disease)
Type VII, muscle deficiency of inability to exercise.
Phosphofructokinase.

Glycogen Metabolism.

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GLYCOGEN METABOLISM

• Glucose is stored as Glycogen in animals & as starch in plants.

• Most of the glycogen metabolism enzymes present in cytoplasm.

• Glycogen metabolism - Glycogenesis (glycogen synthesis), Glycogenolysis

• Major function of liver glycogen is to provide glucose during fasting state.

• Synthesis of glycogen from glucose called glycogenesis

• Phosphoglucomutase catalyses the conversion of glucose 6-phosphate to

• pre excisting glycogen must act as a ‘primer’ to initiate glycogen synthesis.

• It is recently found that in absence of glycogen primer, a specific Protein namely

• Glycogen synthase is responsible for the formation of 1,4-glycosidic linkages.

• The formation of branches is brought about by the action of a branching enzyme,

• Glycogen is further elongated and branched, respectively by the enzymes glycogen

• Breakdown/degradation of stored glycogen in liver and muscle constitutes for

• Enzymes – present in cytosol.

• Glycogen is degraded by breakdown of α-1,4 and α-1,6 linkage.

• The α-1,4-glycosidic bonds are cleaved sequentially by the enzyme glycogen

• Pyridoxal phosphate (PLP- vitamin B6) used as co-enzyme for glycogen

• Branches of glycogen are cleaved by two enzyme activities present on a single

• Glycosyl 4 : 4 transferase activity removes a fragment of three or four glucose

• The remaining molecule of glycogen is again available for the action of

• By the help of Glycogen phosphorylase and de-branching enzyme glucose 1-

• Glucose 6-phosphatase is absent in muscle, some amount of free glucose (8-10% of

• Key enzymes- Glycogen synthase, glycogen phosphorylase

• Hormones- Insulin and glucagon/epinephrine

• Glycogen synthase active in dephosphorylated state.

• Glycogen phosphorylase active in phosphorylated state.

• Insulin favours glucose utilization and decrease glucose level.

• Glucagon favours glucose formation.

• Metabolic defects concerned with glycogen sysnthesis and degradation are

Glycogen Storage Disease Type-I

• Incidence is 1 in 100,000 live births.

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