Glycogen synthesis

Is glycogen made in the fasted or fed state?

Fed (more glucose present)

UDP-glucose

Uridine diphosphate glucose

Monomer used to extend glycogen chain in synthesis

Activated form of glucose

UDP-glucose pyrophosphorylase

Converts glu-1-P to UDP-glucose

Irreversible

Hydrolyzes pyrophosphate

Glycogen synthase

Forms a-1,4 linkages

Removes glucose from UDP-glucose and adds it to C4 on glycogen chain

Needs at least 4 preexisting glucoses in the chain to work

Glycogenin

Synthesizes 4glu primer when making new glycogen molecule

Center of a glycogen molecule

Autoglucosylation

First step in glycogen synthesis

UDP-glucose used to self-glycosylate glycogenin’s Tyr-194 residue

Glycogen branching enzyme

Recognizes glycogen branches at least 11glu long

Cleaves a-1,4 linkage to get 7 glucose chain

Rearranges chain to C6 to make a-1,6 branch

What is the regulatory enzyme for glycogen synthesis?

Glycogen synthase

Glycogen synthase a

Active

R state

Dephosphorylated

Glycogen synthase b

Inactive

T state

Phosphorylated

What enzyme in glycogen synthesis is allosterically activated? What is the allosteric activator?

Glycogen synthase b

Glu-6-phosphate

What hormone(s) inhibit glycogen synthesis?

Epinephrine (exercise)

Glucagon (fasted)

What protein switches from glycogen degradation to synthesis?

Protein phosphatase 1 (PP1)

Dephosphorylation inactivates degradation enzymes and activates synthesis enzymes

What inactivates PP1?

Epinephrine

Glucagon

What hormone(s) stimulate glycogen synthesis?

Insulin (fed, high glucose levels)

Glycogen synthase kinase inactivated; PP1 can dephosphorylate glycogen synthase causing activation

GLUT4 expression increases with insulin signaling, allowing for more import of glucose