Biochemistry
Dr. Aws Hassan
3
rd
Lecture
Glycogen Metabolism
Glycogen molecule :
● Glycogen is the major storage form of carbohydrate in animals .
● Glycogen is stored as globular granules in the cytoplasm of the cells ; mainly in
the liver (10gm/100gm tissue ) and in the muscle (1-2gm/100gm tissue ) .
The total quantity of muscle glycogen is more than liver glycogen because of the
large muscle mass .
● Glycogen molecules are highly branched polymers consisting of D-glucose residues .
The linkage between glucose residues is α-1,4 except at branch points where the
linkage is α-1,6 .
● Each branch chain contains about 12 glucose residues .
● Branching occur at intervals of about every 4 – 6 molecules .
● Branching is so organized that it makes glycogen less space occupying .
● Because of this high branching , the glycogen molecule is capable to store and
deliver glucose units quickly .
Glycogen synthesis (Glycogenesis)
:
● The precursor for glycogen synthesis is activated glucose ( UDP – glucose ) :
glucokinase isomerase
Glucose ------------------
→ Glucose–6–p -----------------→ Glucose–1–p
Glucose
–1–p + UTP ---------------------→ UDP – glucose + PPi
Pyrophosphate
Glycogen degradation ( Glycogenolysis ) :
The enzymes involved in glycogen degradation are :
1-
Glycogen Phosphorylase ( Rate
– Limiting enzyme ) :
This enzyme uses inorganic phosphate (Pi ) to phosphorylate an
d cleave α-1,4
bonds and glucose residues are released as glucose-1-p .
2-
Debranching enzyme : This enzyme has two activities :
a -
4:4 transferase activity
:
C
leaves α-1,4 bond and forms a new α-1,4 bond : removes three of the four
glucose residues remained away from one branch point and transfers it to the
end of the other branch chain .
b -
α
-1,6 glucosidase activity
:
Hydrolyze the last glucose
residue at the branch point ( linked by α-1,6 bond )
and free glucose released .
Notes :
● Degradation of glycogen in both liver and muscle leads to 90% of glucose residues
being released as glucose-1-p and 10% as free glucose .
● In Liver ; Glucose-1-p produced from glycogen degradation is isomerized to
glucose-6-p .Then , inorganic phosphate is cleaved from glucose-6-p by the
enzyme glucose-6-phosphatase (
present in liver & kidney ) and free glucose
is released and enters the blood .
Therefore , liver glycogen is utilized to maintain blood glucose during fasting .
● Muscles do not contain the enzyme glucose-6-phosphatase and therefore cannot
contribute directly to the maintenance of blood glucose .
In muscles , glycogen is degraded to provide ATP for the activity of muscle itself
(muscle contraction) .
Time scale for gluconeogenesis & glycogenolysis
:
■ The liver begins to breakdown its glycogen stores by the process of glycogenolysis
after 2-3 hours after a meal .
■ Glycogenolysis is the major process responsible for maintaining blood glucose
until 18-20 hours fast .
■ The liver begins the process of gluconeogenesis after about 4-6 hours of fasting .
■ Glycogenolysis & Gluconeogenesis contribute equally for maintaining blood glucose
at the period between 18-20 hours of fast .
■ Gluconeogenesis become the major process for maintaining blood glucose after 18-20
hours of fasting .
■ After about 30 hours fast liver glycogen is completely depleted and gluconeogenesis
become the only source of blood glucose .
■ Muscle glycogen is depleted after about 15 minutes of heavy exercise .
Glycogen Storage Diseases ( Glycogenosis )
A group of inherited disorders characterized by deposition of an abnormal type or
quantity of glycogen in tissues .
Type I
–
Von Gierk
’
s disease
:
● The enzyme glucose-6-phosphatase is deficient . Incidence is 1 in 100,000 birth .
● Both liver and renal tubules are loaded with glycogen . Liver enlargement may
lead to cirrhosis .
● Glucose-6-phosphate is accumulated but glucose cannot be released from liver
during overnight fast leading to fasting hypoglycemia .
● Because glucose becomes less available to cells , therefore , the energy is obtained
from fat metabolism and increasing amount of acetyl-CoA is formed which is
mostly utilized in the synthesis of ketone bodies ( ketosis ) .
[ Glycogen synthesis ( glycogenesis ) & Glycogen degradation ( glycogenolysis ) ]