L20 bio
Glycogenesis and glycogenolysis
Learning outcomes:
By the end of the lecture, the students will be able to:
•Define Glycogenesis and glycogenolysis and their importance.
•Differentiate between them.
•Describe steps of Glycogenesis and glycogenolysis.
•Determine the regulation of two processes.
•List examples for glycogen storage diseases.
GLYCOGENESIS
Definition: It is the formation of glycogen from glucose.
Glucose → Glycogen
Site: It occurs in the cytosol of cells
- (except RBCs)
-especially in liver & muscles.
Importance: Storage of excess glucose, or
other hexoses taken in food.
Steps:
▪ UDPG acts as a substrate for glycogen
synthesis.
▪ Glucose is transferred from UDPG to a
glycogen primer forming α-1, 4-glucosidic
bonds.
-The reaction is catalyzed by the enzyme
glycogen synthase (the key enzyme) whose
function is to elongate short branches in the
glycogen tree up to 12 glucose units.
▪ The branching enzyme transfers some of
glucose units from the end of a long branch
to one of glucose units in the middle of an
adjacent long branch forming α-1, 6-glucosidic bond.
A new branch appears on which glycogen synthase can act again.
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L20 bio
Regulation of glycogenesis:
1. Covalent modification: Glycogen synthase is the key enzyme.
It is present in two forms:
-Glycogen synthase (active form) which is dephosphorylated.
-Glycogen synthase (inactive form) which is phosphorylated.
2. Induction and repression of the key enzyme:
• Carbohydrates feeding induce insulin synthesis for the key enzyme (induction) so,
glycogenesis is stimulated.
• Fasting decrease insulin and increase antiinsulin leading to decrease synthesis of the key
enzyme (repression) and hence glycogenesis is inhibited.
3. Allosteric Regulation:
• Glycogen synthase is allosterically activated by Glucose -6-P.
• allosterically inhibited by glycogen molecule.
Glycogenolysis
Definition: It is the breakdown of glycogen into glucose or glucose 6-phosphate.
Site: It occurs in cytosol of cells
- (except RBCs)
-especially in liver & muscles.
Importance:
-In liver: It supplies blood glucose during fasting
less than 18 hours.
-In muscles: It is source of energy during exercise.
Steps:
▪ The phosphorylase enzyme (the key enzyme)
catalyzes the removal of glucose residues from
the outermost chains in the form of G-1-P.
▪ Debranching enzyme catalyzes the hydrolytic
splitting of the α-1, 6- bond so, the phosphorylase
can act again.
(N.B.) G-6-Phosphatase is present in liver, kidneys
& intestines but NOT in muscles.
Liver glycogen can give glucose to blood, but Muscle glycogen cannot give glucose to blood
directly (may give it through Cori’s cycle).
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L20 bio
Regulation of glycogenolysis:
1. Covalent modification:
Phosphorylase is the key enzyme.
It is present in two forms:
-Phosphorylase (active form) which is phosphorylated.
-Phosphorylase (inactive form) which is dephosphorylated.
2. Induction and repression of the key enzyme:
▪ Carbohydrates feeding induce insulin which leads to decrease
synthesis of key enzyme (repression) so glycogenolysis is inhibited.
▪ Fasting decrease insulin and increase anti-insulin which increase synthesis of key enzyme
(induction) so glycogenolysis is stimulated.
3. Allosteric Regulation:
Muscle phosphorylase is allosterically activated by AMP which is increased during muscular
exercise.
Cori’s (glucose -lactate) cycle :
-In contracting muscle glycogen gives G-6-P which by glycolysis gives lactate as there is no O2.
-Lactate diffuses to blood and goes to the liver where lactate is converted to glucose by
gluconeogenesis.
-Glucose can return back to muscles.
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