Glycogen degradation

Glycogen

Highly branched homopolymer of glucose

Present in all tissues

Where are the largest stores of glycogen?

Muscle and liver

Describe the structure of glycogen

a-1,4 chains

a-1,6 branches

Nonreducing ends

Glycogen phosphorylase

Phosphorolyzes glycogen a-1,4 linkages from the nonreducing ends

Creates glu-1-P

Dimer

Phosphorolysis

Addition of Pi to degrade a-1,4 linkages

Transferase

Shifts oligosaccharides away from branch point to increase accessibility to the phosphorylase

a-1,6 glucosidase

Hydrolyzes the branching point on glycogen

Releases FREE glucose (no Pi)

What is the ratio of glu-1-P to glucose produced for the glucosidase reaction?

12:1

Phosphoglucomutase

Converts glu-1-P to glu-6-P

Prepares glycogen derived glucose for glycolysis/use in cell

What is the mechanism for phosphoglucomutase (not liver)?

Ser114 is a Pi group carrier that adds to glu-1-P to create glu-1,6-P, then removes to create glu-6-P

What is the mechanism for phosphoglucomutase in the liver?

Ser114 is a Pi group carrier that adds to glu-1-P to create glu-1,6-BP, then removes to create glu-6-P

Glu-6-P is converted to glucose by glu-6-phosphatase to exit liver and enter bloodstream

How many glucoses can glycogen phosphorylase liberate from the molecule?

8

What enzyme regulates glycogen breakdown?

Glycogen phosphorylase

Glycogen phosphorylase a

Active form

R state favored

Ser14 is phosphorylated

Glycogen phosphorylase b

Inactive form

T state favored

Ser14 dephosphorylated

What is the default state of liver glycogen phosphorylase?

a (active) form

Phosphorylated

R state

How is liver glycogen phosphorylase regulated?

Increased glucose concentration inhibits

Negative regulation

What is the default state of muscle glycogen phosphorylase?

b (inactive) form

T state

How is muscle glycogen phosphorylase regulated?

Increased AMP concentration activates

Positive regulation

What hormone(s) upregulate glycogen phosphorylase and how?

Glucagon, Epinephrine

These signaling pathways activate phosphorylase kinase which in turn activates glycogen phosphorylase

How is phosphorylase kinase activated?

Increased Ca2+ concentration

Phosphorylation

Calmodulin

Delta subunit of phosphorylase kinase

Calcium sensor

Aids in phosphorylase kinase activity

How is glycogen breakdown inhibited?

GTPase activity

Phosphodiesterase activity

Protein phosphatase 1 activity

What does GTPase do?

Inactivates G proteins

What does phosphodiesterase do?

Converts cAMP to AMP

No cAMP = no PKA stimulation

What does protein phosphatase 1 do?

Removes Pi from phosphorylase kinase and glycogen phosphorylase, leading to inactivation