GLYCOGENOLYSIS Glycogen Degradation Almoeiz Yousif Uses of Glycogen

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GLYCOGENOLYSIS Glycogen Degradation Almoeiz Yousif

GLYCOGENOLYSIS Glycogen Degradation Almoeiz Yousif

Uses of Glycogen in Different Organs • Liver: Glucose for other organs. Liver cells

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. Monday, November 2, 2020 Almoeiz Yousif 2

WHEN? Degradation occurs; 1. After some hours without food; when blood glucose levels are

WHEN? Degradation occurs; 1. After some hours without food; when blood glucose levels are low ( fasting state) 2. In muscle during exercise Monday, November 2, 2020 Almoeiz Yousif 3

Functions of GLYCOGENOLYSIS • Regulates blood glucose between meals. Supplies blood glucose for 12

Functions of GLYCOGENOLYSIS • Regulates blood glucose between meals. Supplies blood glucose for 12 – 18 hours of fasting • Gives muscles energy for exercise Monday, November 2, 2020 Almoeiz Yousif 4

WHERE? • In the cytosol of liver and muscle cells Monday, November 2, 2020

WHERE? • In the cytosol of liver and muscle cells Monday, November 2, 2020 Almoeiz Yousif 5

REACTIONS OF GLYCOGENOLYSIS • GLYCOGENOLYSIS starts with glycogen and ends with glucose-6 -phosphate or

REACTIONS OF GLYCOGENOLYSIS • GLYCOGENOLYSIS starts with glycogen and ends with glucose-6 -phosphate or glucose. Glycogen → → Glucose-6 -phosphate /glucose Monday, November 2, 2020 Almoeiz Yousif 6

Glycogenolysis is NOT reverse of glycogenesis ---Monday, November 2, 2020 Almoeiz Yousif glucose 7

Glycogenolysis is NOT reverse of glycogenesis ---Monday, November 2, 2020 Almoeiz Yousif glucose 7

1. Glycogen Phosphorylase Monday, November 2, 2020 Almoeiz Yousif 8

1. Glycogen Phosphorylase Monday, November 2, 2020 Almoeiz Yousif 8

Pyridoxal Phosphate • Muscle glycogen phosphorylase requires a coenzyme pyridoxal phosphate (PLP) Monday, November

Pyridoxal Phosphate • Muscle glycogen phosphorylase requires a coenzyme pyridoxal phosphate (PLP) Monday, November 2, 2020 Almoeiz Yousif 9

Glycogen Phosphorylase • Breaks a α 1 -4 bonds releasing Glucose-1 -P • Requires

Glycogen Phosphorylase • Breaks a α 1 -4 bonds releasing Glucose-1 -P • Requires PLP • STOPS four glucoses before a branch point Monday, November 2, 2020 Almoeiz Yousif 10

2. Debranching Enzyme • The activity of phosphorylase stops 4 glucose residues from the

2. Debranching Enzyme • The activity of phosphorylase stops 4 glucose residues from the branch point. • Debranching enzyme contains 2 activities: • glucotransferase • glucosidase Monday, November 2, 2020 Almoeiz Yousif 11

Debranching Enzyme Monday, November 2, 2020 Almoeiz Yousif 12

Debranching Enzyme Monday, November 2, 2020 Almoeiz Yousif 12

Transferase -1, 6 glucosidase activity of of Debranching enzyme P P P phosphorylase P

Transferase -1, 6 glucosidase activity of of Debranching enzyme P P P phosphorylase P P P Monday, November 2, 2020 Almoeiz Yousif 13

3. Phosphoglucomutase Monday, November 2, 2020 Almoeiz Yousif 14

3. Phosphoglucomutase Monday, November 2, 2020 Almoeiz Yousif 14

4. Glucose-6 -phosphatase • Is an enzyme found in liver and kidney cells Glucose-6

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 -------> Glucose X Monday, November 2, 2020 Almoeiz Yousif 15

LIVER: Glucose-6 -Phosphatase Glc-6 -P -------> Glucose MUSCLE: Glc-6 -P ------X----> Glucose Glycolysis Monday,

LIVER: Glucose-6 -Phosphatase Glc-6 -P -------> Glucose MUSCLE: Glc-6 -P ------X----> Glucose Glycolysis Monday, November 2, 2020 Almoeiz Yousif 16

Glycogen glycogen phosphorylase Pi Glucose-1 -phosphate phosphoglucomutase Glucose-6 -phosphate glycolysis glucose-6 -phosphatase Glucose Pi

Glycogen glycogen phosphorylase Pi Glucose-1 -phosphate phosphoglucomutase Glucose-6 -phosphate glycolysis glucose-6 -phosphatase Glucose Pi X LIVER PATHWAY Monday, November 2, 2020 Almoeiz Yousif 17

Glycogen Pi glycogen phosphorylase Glucose-1 -phosphate phosphoglucomutase Glucose-6 -phosphate X Glucose glycolysis Pyruvate MUSCLE

Glycogen Pi glycogen phosphorylase Glucose-1 -phosphate phosphoglucomutase Glucose-6 -phosphate X Glucose glycolysis Pyruvate MUSCLE PATHWAY Monday, November 2, 2020 Almoeiz Yousif 18

Major Enzymes • Glycogen phosphorylase and • Glycogen debranching enzyme. • The key enzyme

Major Enzymes • Glycogen phosphorylase and • Glycogen debranching enzyme. • The key enzyme is glycogen phosphorylase Monday, November 2, 2020 Almoeiz Yousif 19

Glycogenolysis Regulation 1. HORMONAL REGULATION • GLUCAGON, EPINEPHRINE • Activate glycogen breakdown • INSULIN

Glycogenolysis Regulation 1. HORMONAL REGULATION • GLUCAGON, EPINEPHRINE • Activate glycogen breakdown • INSULIN • Inactivates glycogen breakdown Monday, November 2, 2020 Almoeiz Yousif 20

Active / Inactive form Key Enzyme Glycogen Phosphorylase Monday, November 2, 2020 Active form

Active / Inactive form Key Enzyme Glycogen Phosphorylase Monday, November 2, 2020 Active form (a form) Inactive form (b form) −P Phosphorylated form −OH Almoeiz Yousif Dephosphorylate d form 21

• Glucagon and epinephrine phosphorylate ( and thus activates) glycogen phosphorylase Monday, November

• Glucagon and epinephrine phosphorylate ( and thus activates) glycogen phosphorylase Monday, November 2, 2020 Almoeiz Yousif 22

Hormonal Regulation of glycogen metabolism • Insulin activates glycogen synthase and inactivates glycogen phosphorylase

Hormonal Regulation of glycogen metabolism • Insulin activates glycogen synthase and inactivates glycogen phosphorylase • Glucagon and epinephrine activate glycogen phosphorylase and inactivate glycogen synthase Monday, November 2, 2020 Almoeiz Yousif 23

Glycogen Storage Diseases • Enzyme deficiencies that glycogen metabolism • They are inherited Monday,

Glycogen Storage Diseases • Enzyme deficiencies that glycogen metabolism • They are inherited Monday, November 2, 2020 Almoeiz Yousif affect 24

Symptoms Accumulation of glycogen in tissues • If liver is affected, hypoglycemia results •

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. Monday, November 2, 2020 Almoeiz Yousif 25

Types of Glycogen Storage Diseases Type Type I II IV V VI VIII Monday,

Types of Glycogen Storage Diseases Type Type I II IV V VI VIII Monday, November 2, 2020 Almoeiz Yousif 26

Monday, November 2, 2020 27

Monday, November 2, 2020 27

Type I (Von Gierke’s Disease) • due to deficiency of Glucose 6 phosphatase Monday,

Type I (Von Gierke’s Disease) • due to deficiency of Glucose 6 phosphatase Monday, November 2, 2020 Almoeiz Yousif 28

Symptoms of Von Gierke’s Disease 1. liver cells are loaded with glycogen 2. hepatomegally

Symptoms of Von Gierke’s Disease 1. liver cells are loaded with glycogen 2. hepatomegally 3. hypoglycemia Monday, November 2, 2020 Almoeiz Yousif 29

Monday, November 2, 2020 Almoeiz Yousif 30

Monday, November 2, 2020 Almoeiz Yousif 30

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