Dietary sugars

Starches Pancreatic Amylase Maltose Glucose

Salivary Amylase Maltase

Maltose
Glucose

Glucose Isomerase

Sucrose Sucrase Fructose

Lactase
Lactose Glucose

Glucose Epimerase

Galactose
 Glycogen
Glycogen is a polymer of glucose residues linked by
a(14) glycosidic bonds, mainly
a(16) glycosidic bonds, at branch points

- 1,4 (93%) and - 1,6 (7%)

Branched every 8-12 residues

Glucose is stored as glycogen predominantly in liver

and muscle cells
 1-4 linkage

1-6 linkage

Glycosidic bonds in
glycogen molecule
Glycogenesis Glycogenolysis
 GLYCOGENESIS
Def:- Synthesis of glycogen from D-glucose.

Site mainly cytoplasm of liver and muscle cells.

Steps
1. Synthesis of UDP-glucose.
2. Synthesis of primer to initiate glycogen
synthesis.
3. Elongation of glycogen chains by glycogen
synthase.
4. Formation of branches.
Glycogen Synthase adds glucose residues to glycogen
Synthase cannot start from scratch needs a primer
Glycogenin starts a new glycogen chain, bound to itself
Glycogenin is a protein, and is a self glycosylating
enzyme
-uses UDP glucose to one of its
own tyrosine residues
-Glycosylated glycogenin serves
as a nucleus for synthesis of
glycogen
Glycogenesis (Contd)
Glycogen branching enzyme then introduces
branch points
 Significance of Glycogen
1.Liver glycogen - storage and transport of hexose units
for maintenance of blood glucose especially between
meals.
After 12-18hours of fasting, liver becomes almost
depleted of glycogen.
2.Muscle glycogen readily available source of hexose
units for glycolysis within the muscle itself.
3. High liver glycogen depresses deamination of amino
acid which are sources of protein synthesis
4. High liver glycogen depresses rate of ketogenesis.
5. High glycogen content favors detoxification of
many substances by acetylation of glucuronide.
6. Glycogen rich liver protects against harmful
effects of many poisons.
7. Inherited deficiency of specific enzymes of
glycogen metabolism leads to glycogen storage
diseases.
 Regulation of Glycogenesis
Glycogen synthase active form is
dephosphorylated
Glycogen synthase - inactive form is phosphorylated

Insulin dephosphorylates glycogen synthase

Glucagon (not in muscle) & epinephrine
phosphorylates glycogen synthase through cAMP
Insulin induces key enzyme glycogen synthase
 Regulation of Glycogenesis
Allosteric control
G6P Glycogen
+ _
Glycogen synthase

Covalent modification
Insulin Inhibitor 1 P (a)
+ _

Glycogen Protein phosphatase Glycogen

synthase (a) Protein kinase synthase (b)
-P +P
+
cAMP + Inhibitor 1 P
 GLYCOGENOLYSIS
Definition
Process of break down of glycogen to glucose in the
liver or to G6P in the muscle.

Site Liver and muscle

Glycogen Breakdown
Glycogenolysis (Glycogen
Degradation)
Glycogenolysis
 Steps in Glycogenolysis
Shortening of chains by phosphorylase
Removal of branches by debranching enzyme
Conversion of G1P to G6P by mutase
G6P to glucose by glucose 6 phosphatase
Glycogenesis Glycogenolysis
 Regulation of Glycogenolysis
Glycogen phosphorylase key enzyme
Exists in 2 forms
Phosphorylase B (inactive)-dephosphorylated
Phosphorylase A (active) - phosphorylated
Phosphorylase B is converted to Phosphorylase
A by Phosphorylase Kinase

Active form - phosphorylated

Key enzyme glycogen phosphorylase
Active form phosphorylated form

Allosteric control
AMP (Muscle) ATP

+ _
Glycogen
phosphorylase

AMP does not activate liver phosphorylase

but activate muscle phosphorylase
 Covalent control
Liver Glucagon/ Epinephrine
through
cAMP
+
Glycogen Protein kinases Glycogen
Phosphorylase(b) Phosphorylase(a)

Glucagon acts only on the liver. Glycogenolysis

Epinephrine acts on both liver & muscle
Covalent control
Liver Glucagon / Epinephrine
through

cAMP
+
Phosphorylase kinase b Phosphorylase kinase a

Glcogen phosphorylase b Glcogen phosphorylase a

Glycogenolysis

Glucagon acts only on the liver.

Epinephrine acts on both liver & muscle
 Glycogen Storage Diseases
A group of inherited disorders caused by a defect in
glycogen metabolism characterized by impaired
conversion of glycogen to free glucose resulting in the
accumulation of normal and abnormal glycogen in
tissues.
The most common form is Type Ia, or Von Gierke
Disease. All GSD are inherited as an autosomal
recessive trait except two, phosphoglycerate kinase
deficiency (a muscle glycogenoses) and
liver phosphorylase kinase deficiency ( a Hepatic
glycogenoses), both of which are X-linked diseases

Most are childhood disorders

GSD involving principally the liver (hepatic glycogenoses)

and those principally involving the muscles (muscle
glycogenoses).
 Glycogen Storage Diseases
Type I Von Gierkes -glucose 6
disease phosphatase
Type II Pompes - 1-4 glucosidase
disease
TypeIII Forbes -debranching enzyme
disease
Type IV Amylopectinosis -branching enzyme
Type V Mc Ardles -muscle
disease phosphorylase
 Type VI Hers disease -Liver
phosphorylase
Type VII- Taruis disease -PFK in muscle and
RBC
Type VIII -Liver phosphorylase
kinase
Type IX -Liver & muscle
phosphorylase kinase
Type X -cAMP dependent
protein kinase A
- Glycogen storage disorders are classified according to
which enzyme is lacking or not working normally and also
which part of the body is affected by the disease.
-Glycogen storage disorders mostly tend to affect liver
and muscles. However, some glycogen storage disorders
can affect other parts of the body such as the kidney, heart,
blood vessels, nervous system and bowel

Type I glycogen storage disorder is the most

common. About one quarter of people who have
glycogen storage disorder have type I.
 Glycogen-storage disease Ia is caused by deficient
activity of the enzyme glucose-6-phosphatase
Glycogen-storage disease Ib is caused by deficiency
of glucose-6-phosphate translocase, which is
responsible for importing glucose-6-phosphate from
the cytosol to the interior of the microsome, thus
bringing substrate into contact with enzyme.
 Glycogen-storage disease type I
- Because free glucose is the product of the hepatic
glucose-6-phosphatase reaction, either type leads to
accumulation of liver glycogen, accompanied by
fasting hypoglycemia.

Hepatomegaly, the natural consequence of glycogen

accumulation, is the clinical hallmark of the disease.
Symptoms - in addition to glycogen accumulation
hypoglycemia (low blood glucose) when fasting,
liver enlargement.
liver dysfunction and early death
muscle cramps with exercise
inability to exercise
 Learning outcome
Describe the structure of glycogen
Describe the synthesis & degradation of glycogen
Compare & contrast synthesis & breakdown of
glycogen
Describe the regulation of glycogenesis &
glycogenolysis
Explain the glycogen storage diseases