Biochem423 Glycogen Synthesis

Phosphoglucomutase

Catalyzes the isomerization of glucose-6-phosphate to glucose-1-phosphate

UDP-Glucose pyrophosphorylase

Forms UDP-Glucose (activated) from G1P

Adds UMP to G1P —> Releases Pyrophosphate which dissociates into 2 inorganic phosphate via inorganic phosphatase

Glycogen synthase

Catalyzes the addition of UDP-Glucose to glycogen (releases UDP)

Requires a chain of four or more units

Can ONLY form alpha(1,4) bonds

Adds Glucose to a non-reducing end of glycogen

Glycogenin

Forms glucose primers of at least 4 monomers

Catalyzes addition of glucose chains (from UDP-Glucose) to its Tyr R-groups.

Glycogen extends glycogen primer via alpha(1,4) bonds

Branching Enzyme

Forms branches in glycogen

Transfers ~ 7 unit chunks from branches > 10 units long

Connects to chain via alpha(1,6) bond

Glycogen phosphorylase

Catalyzes glucose release from non-reducing ends

Breaks glycosidic alpha(1,4) bonds via phosphorylase (with a phosphate group)

Results in the release of G1P (can be isomerized by phosphoglucomutase to G6P —> Glucose)D

Debranching Enzyme

Cleaves alpha(1,4) bond and transfers trisaccharides to other branches, forming an alpha(1,4) bond

Cleaves final glucose residue of the previous branch at the alpha (1,6) bond

Cyclic cascade

When glucagon is secreted by the pancreas, it causes a phosphorylation cascade to occur, phosphorylating many metabolic enzymes

When insulin is secreted by the pancreas, it causes a dephosphorylation cascade to occur, dephosphorylating many metabolic enzymes

Glucagon’s effect on gluconeogenesis enzymes

Glucagon —> cAMP → p-PKA —> p-Phosphorylase kinase —> p-Glycogen phosphorylase —> glycogen degradation activated

Glucagon —> cAMP —> p-PKA —> other kinases —> p-Glycogen Synthase —> inhibits glycogen synthesis

Insulin’s effect on gluconeogenesis enzymes

Insulin —> PP1 active —> dephosphorylates many enzymes —> inhibits glycogen degradation

Insulin —> PP1 active —> dephosphorylates GS —> glycogen synthesis