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Course: Nutrition and Metabolism
Part (1): Metabolism of Carbohydrates Lecture (6): Glycogenolysis
Rihab SiddigMobile: +249918191982
Uses of Glycogen in Different Organs
• Liver: Glucose for other organs.
Liver cells do not use this glucose for their own energy needs.
• Muscle: Glucose for muscle use during exercise.
WHEN?
• Glycogen degradation
occurs;
1. After some hours without
food; when blood glucose
levels are low ( fasting
state)
2. In muscle during exercise
Functions of
GLYCOGENOLYSIS
• Regulates blood glucose
between meals. Supplies blood
glucose for 12 – 18 hours of
fasting
• Gives muscles energy for
exercise
WHERE?
•In the cytosol of liver
and muscle cells
REACTIONS
OF GLYCOGENOLYSIS
• GLYCOGENOLYSIS starts with glycogen and ends with glucose-6-phosphate or glucose.
Glycogen → → → → Glucose-6-phosphate/glucose
Glycogenolysis is NOT reverse of glycogenesis
glucose
----------
1. Glycogen Phosphorylase
Pyridoxal Phosphate
• Muscle glycogen phosphorylase requires a coenzyme pyridoxal phosphate (PLP)
Glycogen Phosphorylase
• Breaks a α1-4 bonds releasing Glucose-1-P
• Requires PLP
• STOPS four glucoses before a branch point
2. Debranching Enzyme
• The activity of phosphorylase stops 4 glucose residues from the branch point.
• Debranching enzyme contains 2 activities: –glucotransferase–glucosidase
Debranching Enzyme
-(1—>4) transglycosylase
Glucose-(1—>6) glucosidase
Limit Branch (4 residues)
(group transfer reaction)
P
P P P P
P
P
Pphosphorylase
Transferase activity of
Debranching enzyme
-1,6 glucosidase activity of
Debranching enzyme
3. Phosphoglucomutase
Glucose–1–P Glucose–6–P
4. Glucose-6-phosphatase
• Is an enzyme found in liver and kidney cells
Glucose-6-Phosphatase
Glc-6-P --------------> Glucose
• NOT found in muscle cells.
Glc-6-P --------------> GlucoseX
MUSCLE:
Glc-6-P ------ --------> Glucose
LIVER:
Glucose-6-Phosphatase
Glc-6-P --------------> Glucose
Glycolysis
X
Piglycogen
phosphorylase
phosphoglucomutaseglucose-6-phosphatase
Glucose-1-phosphate
Glucose-6-phosphate
Glycogen
Glucose
Xglycolysis
LIVER PATHWAY
Pi
MUSCLE PATHWAY
glycolysis
Pyruvate
Piglycogen
phosphorylase
phosphoglucomutase
Glucose-1-phosphate
Glucose-6-phosphate
Glycogen
GlucoseX
Major Enzymes
Glycogen phosphorylase
and
Glycogen debranching enzyme.
The key enzyme is glycogen
phosphorylase
Glycogenolysis Regulation
1.HORMONAL REGULATION
• GLUCAGON, EPINEPHRINE
–Activate glycogen breakdown
• INSULIN
– Inactivates glycogen breakdown
Active / Inactive form
Key Enzyme Active form
(a form)
Inactive form
(b form)
Glycogen
Phosphorylase
−P
Phosphorylated
form
−OH
Dephosphorylated
form
• Glucagon and epinephrine phosphorylate ( and thus activates) glycogen phosphorylase
Key Enzyme Active form
(a form)
Inactive form
(b form)
Glycogen
Synthase
−OH
Dephosphorylated
form
−P
Phosphorylated
form
Glycogen
Phosphorylase
−P
Phosphorylated
form
−OH
Dephosphorylated
form
Hormonal Regulation
• Insulin dephosphorylates bothenzymes
• Glucagon and epinephrine phosphorylate both enzymes
Reciprocal regulation of glycogen
metabolism
• Insulin activates glycogen synthase and inactivates glycogen phosphorylase
• Glucagon and epinephrine activate glycogen phosphorylase and inactivate glycogen synthase
Glycogenesis vs Glycogenolysis
Glycogen Storage Diseases:
•Enzyme deficiencies that affect glycogen metabolism•They are inherited
Symptoms
Accumulation of glycogen in tissues
• If liver is affected, hypoglycemia results
• If muscle is affected inability to exercise
• In the most severe diseases, death at an early age.
Types of Glycogen Storage Diseases
Type I
Type II
Type III
Type IV
Type V
Type VI
Type VII
Type VIII
Type I (Von Gierke’s Disease)
• due to deficiency of Glucose 6 phosphatase
glycogen
glucose-1-P
Glucose-6-Phosphatase
glucose-6-P glucose + Pi
fructose-6-P
Phosphofructokinase
fructose-1,6-bisP
Glycolysis continued
Type I (Von Gierke’s Disease)
Symptoms of Von Gierke’s Disease
1. liver cells are loaded with glycogen
2. hepatomegally
3. hypoglycemia
Glycogen Storage Disease Symptoms, in addition to
glycogen accumulation
Type I, liver deficiency of
Glucose-6-phosphatase (von
Gierke's disease)
hypoglycemia (low blood
glucose) when fasting, liver
enlargement.
Type IV, deficiency of
branching enzyme in various
organs, including liver
(Andersen's disease)
liver dysfunction and early
death.
Type V, muscle deficiency of
Glycogen Phosphorylase
(McArdle's disease)
muscle cramps with exercise.
Type VII, muscle deficiency of
Phosphofructokinase.
inability to exercise.
Thank you