Glycogen metabolism in muscle and liver

Question 1

Glycogen

Answer 1

Polysaccharide storage form of glucose

Stored in granules predominantly in muscle and liver

Liver glycogen maintains plasma glucose

Muscle glucose sustains muscle contraction

Question 2

Structure of glycogen

Answer 2

Found in granules within cells

Highly branched polysaccharide of glucose

(a-1,4)linked glucose molecules with an (a-1,6)branch every 8-14 glucose residues

Lots of ends for phosphorylase and glycogen synthase to act on

Question 3

D glucose

Answer 3

Natural form used by animal cells

Question 4

Glycogen brakdown

Answer 4

Glycogen-> gluc-1-phosphate-> gluc-6- phosphate

Second reaction catalysed by phosphoglucomutase

Question 5

Glycogen breakdown in muslce

Answer 5

Glycogen-> gluc 1 phosphate-> gluc 6 phosphate -> pyruvate -> lactate and CO2

Question 6

Glycogen breakdown in liver

Answer 6

Glycogen-> gluc 1 phosphate-> gluc 6 phosphate -> glucose

Liver can do this because it expresses glucose 6 phosphatase which muscle does not

Question 7

Mechanism of glucose breakdown

Answer 7

The a-1,4 linkages broken by phosphorolysis catalysed by glycogen phosphorylase

It removes single units from non-reducing ends of glycogen to form glucose-1-phosphate

Question 8

Phosphorylase

Answer 8

Breaks a-1,4 links up to 4 glucose units from branch point

Question 9

Transferase

Answer 9

Activity of debranching enzyme

Removes 3 residues from branch and transfers them to end of another chain in a-1,4 linkage

Question 10

a-1,6 glucosidase

Answer 10

Removes single glucose unit left at branch

Activity of debranching enzyme

Question 11

Cleavage of a-1,6 linkages at branch points

Answer 11

a-1,6 linkages broken by a different a-1,6 glucosidase

Cleaves bond to form free glucose by hydrolysis

Question 12

Glycogen synthesis from UDP glucose

Answer 12

Glucose (ADP) (Hexokinase) –>

Glucose 6 phosphate (phosphoglucomutase) –>

Glucose 1 phosphate (UTP) –>

UDP glucose (glycogen synthase) –>

Glycogen (n) - glycogen (n+1)

Question 13

How glycogen synthesis starts

Answer 13

Priming function carried out by glycogenin protein

UDP glucose donates first glucosyl residue and attaches to tyrosine in glycogenin

Remaining glucose units added in a-1,4 linkage from UDP glucose

Question 14

Introduction of branches

Answer 14

Glycogen synthase extends chain in a-1,4 linkage but can’t made branches

Branching enzyme transfers block of 7 residues from growing chain to create new branch with a-1,6 linkage

New branch must not be within 4 residues of existing branch

Question 15

Glycogen as energy store

Answer 15

Enzymes phosphorylase and glycogen synthase very sensitive to regulation by hormones, stress, muscle contraction

Branched structure means large number of ends

Bad store because hydrophilic and associates with water

Question 16

Acceleration of glycogen mobilisation

Answer 16

In liver during starvation, when glucose is required for glycolysis by the brain and red blood cells

In muscle to fuel glycolysis during vigorous exercise

Question 17

Activation of glycogen synthesis

Answer 17

To replenish liver glycogen stores after feeding or muscle stores when exercise ceases

Pathway for glycogen synthesis not simple reversal of breakdown and requires energy input

Question 18

AMP regulation of phosphorylase

Answer 18

Present when ATP is depleted during muscle contraction

Activates phosphorylase

Question 19

ATP and glucose 6 phosphate regulation of phosphorylase

Answer 19

Both compete with AMP binding

Inhibit phosphorylase

Sings of high energy levels

Glycogen breakdown inhibited when these are high

Question 20

Glucose 6 phosphate and glycogen synthase

Answer 20

Allosterically activates glycogen synthase

Glycogen synthesis is activated

Question 21

Regulation of glycogen metabolism by covalent modification

Answer 21

Mediated by addition of phosphate group

Addition of phosphate group is known as phorphorylation and catalysed by protein kinase

Reversible modification; removal of phosphate catalysed by protein phosphatases

Question 22

cAMP dependent phosphorylation of phosphorylase

Answer 22

cAMP cascade results in phosphorylation of serine hydroxyl of muscle glycogen phosphorylase

Promotes transition to active site

Phosphorylated enzyme less sensitive to allosteric inhibitors

If cellular ATP and glucose 6 phosphate high, phosphorylase will be activated

Question 23

a

Answer 23

Active enzyme

Independent of allosteric regulators

e.g. phosphorylated form of glycogen phosphorylase

Question 24

b

Answer 24

Enzyme dependent on local allosteric controls

e.g. dephosphorylated form of glycogen phosphorylase

Question 25

Catabolic reactions and enzymes

Answer 25

The phosphorylated form of the enzyme is the active form

Question 26

Anabolic reactions and enzymes

Answer 26

The phosphorylated form is the inactive form