Glycogen Metabolism

Question 1

what is glycogen?

Answer 1

the storage form of glucose

Question 2

when do we need glucose?

Answer 2

glucose is the only source of energy for cells lacking mitochondria and is essential in exercising skeletal muscles as well as brain

gluconeogenesis can provide glucose for the cell’s energy needs in absence of adequate dietary intake or during conditions like exercise, it can’t always meet the imitate needs

Question 3

what’s the general structure/makeup of glycogen?

Answer 3

it’s a polymer of several glucose molecules with a protein , glycogenin, present in its very core

individual glucose molecules are joined by alpha 1,4-glyycosidic bonds

at about every 11th residue in the glycogen molecule you will encounter a branch that’s formed by an alpha 1,6-glycosidic linkage

the terminal ends of both the linear chain and the branch will have a non-reducing glucose molecule that has an -OH group bound to the 4th carbon

Question 4

what is the purpose of glycogenin?

Answer 4

it’s the protein in the middle of glycogen

necessary for glycogen synthesis to begin but remains in the core of the molecule

Question 5

can glucose be directly used for chain synthesis in glycogen?

Answer 5

no, it doesn’t have that kind of energy so it has to be activated first

glucose is first converted into UDP glucose (an active donor)

Question 6

what is the second step in glycogen synthesis?

Answer 6

new glucosyl units are added to the non-reducing terminal residues of the glycogen molecule

the glucose from UDP-glucose binds to this residue to form alpha-1,4-glucosidic linkage

catalyzed by glycogen synthase

Question 7

does glycogen synthesis need a primer?

Answer 7

yes

Question 8

what is the function of glycogenin in glycogen synthesis?

Answer 8

initial synthesis of glycogen starts with this protein which forms the core of the molecule

it makes the primer! glycogenin also acts as an enzyme, glycosyl transferase, which adds 8 glucose units sequentially to a specific tyrosine residue in the protein - UDP glucose is the donor –> once the primer is formed glycogen synthase takes over and extends by adding further glucose molecules normally

Question 9

how does glycogen synthase extend the glycogen chain?

Answer 9

1. starts from the primer and uses UDP-glucose as the donor
2. glucose molecules are added to the linear core
3. once more than 11 glucosyl residues are joined via alpha-1,4-glycosidic linkage by glycogen synthase a branch is created
4. a branch starts with the involvement of another protein, branching enzyme - branching enzyme transfers a block of residues by breaking off the alpha-1,4-glycosidic linkage and forming an alpha-1,6-glycosidic linkage
5. meanwhile, glycogen synthase keeps adding more residues to both the new chain and the linear chains

Question 10

why is glycogen branching important?

Answer 10

it increases the stability of glycogen and at the same time creates a large number of terminal residues

terminal residues are important for the function of glycogen synthase as well as the enzyme that starts degradation (glycogen phosphorylase)

branching increases both synthesis and degradation

Question 11

how does glycogen degradation happen?

Answer 11

glycogen phosphorylase cleaves glycogen with the addition of orthophosphate (HPO4-2) to yield glucose 1-phosphate

phosphorylase then catalyzes the sequential removal of glycosyl residues from the non-reducing ends of the glycogen molecule

**the non-reducing end is the one with a free hydroxyl group on carbon 4! in synthesis, this is where glucose molecules are added on to the chain

Question 12

why is glucose 1-phosphate formed in glycogen degradation instead of free glucose?

Answer 12

the energy in the glycosidic bonds are preserved by converting them into the phosphorylation bonds

also glucose 1-phosphate can’t leave the cell but free glucose molecules can

Question 13

can glycogen phosphorylase breakdown glycogen by itself?

Answer 13

no, it can’t breakdown the 1,6-glycosidic bonds at the bran points

actually it stops working when it reaches a terminal residue that’s 4 residues away from a branch point aka phosphorylase would stop working after releasing only 6 glucose molecules

Question 14

wen are branches form in glycogen?

Answer 14

every 11 residues

Question 15

how does the rest of glycogen get degraded after glycogen phosphorylase stops working?

Answer 15

2 more enzymes: transferase and alpha-1,6-glucosidase

1. enzyme transferase shifts a block of 3 glucosyl residues from an outer branch to another which leaves a single glucose residue exposed
2. the lone glucose residue linked by an alpha 1,6-glycosidic bond so alpha-1,6-glucosidase aka debranching enzyme, hydrolyzes the alpha-1,6-glycosidic bond and a FREE glucose molecule is released
3. the free glucose is immediately phosphorylated by hexokinase to glucose 6-phosphate

Question 16

what happens to all the glucose 1-phosphate molecules released buy the action of phosphorylase?

Answer 16

the enzyme phosphogluctomutase converts these glucose 1-phosphate molecules into glucose 6-phosphate which can be redirected towards glycolysis (happens in the muscles)

OR

glucose-6-phosphate can be hydrolyzed by the enzyme glucose 6-phosphatase to form new glucose molecules (happens in the liver)

**glucose 6-phosphatase is also the enzyme in the last step of gluconeogeneis!

Question 17

where does glycogen synthesis specifically start?

Answer 17

glucose residues are added to a tyrosine residue in the protein glycogenin

more glucose residues are added once a primer is formed

Question 18

what does glycogen synthesis start with?

Answer 18

the enzyme glycogen synthase and glycogenin as a primer and UDP-glucose