GLYCOGEN METABOLISM Almoeiz Yousif GLYCOGEN STRUCTURE Glycogen a

. GLYCOGEN METABOLISM Almoeiz Yousif

GLYCOGEN STRUCTURE • Glycogen: a highly branched polysaccharide of glucose. • Branches every 8 -12 residues • Chains have glycosidic α 1 4 links. • Branches have α 1 6 links. Tuesday, December 1, 2020 2

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What Percent of These Organs is Glycogen? • Liver - 6% glycogen • Muscle - 1% glycogen Most body glycogen is found in the muscle because of bigger weight of muscle. Tuesday, December 1, 2020 4

Cellular Site of Glycogen? Glycogen is stored in the cytosol of muscle & liver cells as granules. Tuesday, December 1, 2020 5

Uses of Glycogen in Different Organs • Liver: Glucose for bloodstream. Liver cells do not use this glucose for their own energy needs. • Muscle: Glucose for muscle use during exercise. Tuesday, December 1, 2020 6

Glycogen Metabolism • Glycogenesis= Glycogenesis • synthesis of glycogen from glucose. • Glycogenolysis= Glycogenolysis • degradation of glycogen to give glucose. Tuesday, December 1, 2020 7

GLYCOGENESIS Glycogen Synthesis

WHEN? • Glycogen synthesis occurs after a meal • when blood glucose levels are high ( fed state) • High glucose levels cause secretion of insulin. • Insulin encourages synthesis of glycogen ( anabolism). Tuesday, December 1, 2020 9

WHERE? • In the cytosol of liver and muscle cells. Tuesday, December 1, 2020 10

REACTIONS OF GLYCOGENESIS • GLYCOGENESIS starts with glucose and ends with glycogen. Glucose → → → glycogen Tuesday, December 1, 2020 11

1. Phosphorylation of Glucose • The starting substrate is glucose which is converted to glucose-6 - phosphate. glucose → glucose-6 -phosphate • The enzyme is hexokinase in muscle and glucokinase in liver Tuesday, December 1, 2020 12

2. Phosphoglucomutase • Glucose-6 -phosphate is then converted to glucose-1 -phosphate by the enzyme phosphoglucomutase. • This is a reversible reaction Tuesday, December 1, 2020 13

3. Activation of Glucose UDP-glucose is active glucose. It is formed from glucose-1 -phosphate: glucose-1 -phosphate + UTP UDP-glucose + 2 Pi The enzyme is called UDP-glucose pyrophosphorylase. Tuesday, December 1, 2020 14

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UDP-Glucose (Active Glucose ) is very important for glycogenesis Tuesday, December 1, 2020 16

4. Glycogen Synthase • Glycogen Synthase adds glucoses to each other • Synthesis cannot start from scratch, it needs a primer Tuesday, December 1, 2020 17

Glycogenin (protein) initiates glycogen synthesis. Glycogenin is an enzyme that catalyzes attachment of glucose molecules ( forms a primer) Tuesday, December 1, 2020 18

Glycogen Synthase • Synthase then adds glucose to the primer. Tuesday, December 1, 2020 19

Glycogen Synthase Activity Tuesday, December 1, 2020 20

5. Branching Enzyme • Branching enzyme then introduces branch points. After every 11 glucose residues, branching enzyme cuts off about 7 glucoses and forms a branch. Tuesday, December 1, 2020 21

MAJOR ENZYMES • Glycogen synthase and branching enzyme • Glycogen synthase is the key enzyme in glycogenesis i. e. it can be regulated. Tuesday, December 1, 2020 22

Glucose Hexokinase (muscle) Glucokinase (liver) ATP ADP Glucose-6 -phosphate (Glucose)n+1 UDPGlucose Phosphopyrophosphorylase glucomutase UDP-glucose Glucose-1 -phosphate Glycogen Synthase UTP PPi Pathway of glycogenesis Tuesday, December 1, 2020 23

HORMONAL REGULATION • INSULIN – Turns on glycogen synthesis • GLUCAGON, EPINEPHRINE – Turn off glycogen synthesis Tuesday, December 1, 2020 24

Glycogen Synthase a and b Key Enzyme Active form (a form) Glycogen −OH Synthase Dephosphorylated form Tuesday, December 1, 2020 Inactive form (b form) −P Phosphorylated form 25