Glycogen synthesis and regulation

Question 1

Properties of glucose and monosaccharides

Answer 1

Approx 10g in plasma
Osmotically active
Immediate energy source

Question 2

Properties of glycogen and polysaccharides

Answer 2

Approx 400g in tissues, higher conc in liver
Low osmolarity
Medium term fuel store

Question 3

Role of glycogen in liver glucose homeostasis

Answer 3

Maintains blood glucose under control of insulin and glucagon
Sensitive to blood glucose conc

Glycogen => Glucose 6 phosphate => Glucose + Pi

Question 4

Glycogen in muscle fuel for excercise

Answer 4

Sensitive to adrenaline, calcium, AMP, ATP
Muscle sensitive to energy needs of tissue, does not affect [blood glucose]

Glycogen => Glucose 6 phosphate => Energy for contraction => Lactate

Question 5

Glycogen’s branched structure

Answer 5

Terminal residues at the end of branched chains
All branch from reducing end of polymer
Has a 1,4 and a 1,6 linkages

Question 6

Types of linkage in glycogen

Answer 6

a 1,4 glycosidic linear linkages

a 1, 6 glycosidic branched linkages

Question 7

Features of any biosynthesis pathway

Answer 7

ATP/GTP/UTP needed as cofactors to drive reactions forwards
One or more enzyme reactions will be irreversible and alternative enzymes are used for the opposite direction
Enzyme reactions at the beginning or end of pathway are regulated

Question 8

First stage of glycogen synthesis from glucose

Answer 8

Glucose =Hexiokinase/glucokinase (liver) + ATP => Glucose 6 phosphate + ADP

Glucose 6 phosphate <=phosphoglucomutase=> glucose 1 phosphate

Question 9

Formation of UDP glucose

Answer 9

Glucose 1 phosphate + UTP =transferase=> UDPglucose + PPi

Question 10

Addition of glucose unit to protein primer

Answer 10

UDPglucose + glycogenin (protein primer) =glycogen synthase=> UDP + glucose glycogenin

This continues until there is a chain of glucose molecules attached to glycogenin

Question 11

How are the branch points introduced to the glucose chain

Answer 11

Branching enzymes act on the glucose chain and form a 1, 6 bonds to create a branch

Question 12

Glycogen synthase regulation

Answer 12

Active, glycogen synthase a
+ protein kinase + ATP
Inactive, glycogen synthasePi

Inactive glycogen synthasePi b
+protein phosphatase
Active, glycogen synthase a

Question 13

Differences between kinase, phosphatase and phosphorylase

Answer 13

Kinase, adds high energy phosphates to molecules
Phosphorylase, adds low energy phosphates to molecules
Phosphatase, removes Pi from molecules

Question 14

Glycogen breakdown

Answer 14

Glycogen chain =Pi + glycogen phosphorylase=> breaks glycosidic bonds

Sites of phosphorylase act on long branches, short branches remain after enzyme action
Removal of glucose units from branched units needs debranching enzymes

1,6 glycosidic bonds hydrolyses so glycogen phosphorylase can act on resulting straight chain

Question 15

How is free glucose released from glycogen

Answer 15

Glycogen breakdown by phosphorylase => production of glucose 1 phosphate

Glucose 1 phosphate =mutase=> glucose 6 phosphate =glucose 6 phosphatase (liver only)=> glucose

Glucose 6 phosphate can enter glycolysis in muscle

Question 16

Glycogen phosphorylase regulation

Answer 16

Active, phosphorylase a (Pi)
+protein phosphatase
Inactive, phosphorylase b

Inactive, phosphorylase b
+protein kinase + Pi
Active, phosphorylase a (Pi)

Question 17

Conversion of ATP=>cAMP=> AMP

Answer 17

GCPR, active A (GTP=>GDP)
ATP=adenylyl cyclase=> cAMP

Active cAMP, activates protein kinase A
Protein + ATP = PKA=> Protein PO4 + ADP

cAMP =phosphodiesterase + H2O=> AMP

Question 18

cAMP dependent reactions

Answer 18

AT
Channels
Secretion from microtubules
Enzymes for lipid and glycogen breakdown
Protein synthesis
Ca2+ transport

Question 19

Coordinated regulation of synthesis/breakdown

Answer 19

Active glycogen synthetase
+Protein kinase, ATP
Inactive glycogen synthetase (Pi)

Inactive glycogen synthetase (Pi)
+Protein phosphatase
Active glycogen synthetase

Adrenaline acts on muscles
Glucagon acts on liver
Insulin acts on both

Adrenaline and glucagon stimulates protein kinase action
Insulin stimulates protein phosphatase action

Question 20

Additional controls of the liver in the coordinated regulation of synthesis/breakdown of glycogen

Answer 20

Responds to insulin, glucagon

When glucose is high, binds to glycogen phosphorylase and inactivates it

Question 21

Coordinated regulation of synthesis/breakdown of glycogen in muscle

Answer 21

When contracting, Ca2+ released into sarcoplasmic reticulum
Ca2+ binds the calmodulin domain of glycogen phosphorylase kinase and activates the enzyme
This activates phosphorylase and glycogen is degraded providing energy for contracting muscle

Question 22

Coordinated regulation of synthesis/breakdown of glycogen in the prolonged exercise of muscle

Answer 22

[ATP] falls, {AMP] rises
AMP, allosteric activator of glycogen phosphorylase
Glycogen degradation continues without need for hormonal interaction
ATP allosteric inhibitor, so that when energy levels are high, glycogen breakdown starts

Question 23

Glycogen storage diseases, Von Gierkes
Defective enzyme
Clinical symptoms

Answer 23

Glucose 6 phosphatase

Enlarged liver, hypoglycaemia

Question 24

Glycogen storage diseases, Pompes
Defective enzyme
Clinical symptoms

Answer 24

Lysosomal glycosidase

Muscle weakness, cardiac failure

Question 25

Glycogen storage diseases, McArdles
Defective enzyme
Clinical symptoms

Answer 25

Glycogen phosphorylase

Exercise intolerance