Glycogen metabolism

Question 1

Tissue specific control

Answer 1

In muscle:
Superimposition on phosphorylation by allosteric control through Ca and AMP
Ca2+ signals muscle contraction, it binds to phosphorylase b kinase, which activates it into active form (a). This also occurs with AMP, it accumulates in contracting muscle.

When ATP levels are adequate, ATP will bind allosterically, to inactivate phosphorylase.

Question 2

Control of liver phosphorylase

Answer 2

Blood Glc low:
Glucagon is released into the blood stream, reaches hepatocyte, signals the cascade. Effectively, Glucagon stimulates activation of phosphorylase kinase b to a (active)

Normal Glc:
Glc allosterically binds to phosphorylase, it goes through allosteric modification, making it less active. The serine residue becomes more susceptible to be acessed by phosphatase. Insulin can further inactivate phosphorylase.

Question 3

Epinephrine and Glucagon

Answer 3

Epinephrine stimulates breakdown of Glycogen in the liver and muscle, Glucagon only stimulates the liver.

Question 4

Glycogen synthase

Answer 4

Glycogen synthase a is the active form
Glycogen synthase kinase 3 (GSK3) inactivates glycogen synthase by phosphorylasetion of 3 Serine.

GSK3 is regulated by insulin.

GSK3 requires prior phosphorylation by casein kinase (CKII)

Muscle:
Adrenaline activates PKA.
PKA phosphorylates glycogen targeting protein cause PP1 dissociation from glycogen.

GSK3 inactivation:
It has a pseudosubstrates that can phosphorylate itself and fold into the active site of the enzyme. Ser cannot access for phosphorylation.

Question 5

Blood Glc regulates liver glycogen metabolism

Answer 5

Infusion of glucose into bloodstream leads to inactivation of phosphorylase. Followed by glycogen synthase activation in the liver.