Glycogen synthesis and breakdown

[WG21:p292]

Glycogen

Glycogen is a branched glucose polymer with 2 types of links

1. 1:4alpha
   * provides elongation
2. 1:6alpha
   * provides branching

 

Glycogen synthesis and breakdown

Glycogen synthesis

Glucose 6-phosphate

[Phosphoglucomutase]

---> Glucose 1-phosphate

[UDPGlc pyrophosphorylase]

===> Uridine diphosphate glucose (UDPGlc)

[Glycogen synthase]

===> Glycogen

 

Glycogen breakdown

Glycogen

[Phosphorylase a]

===> Glucose 1-phosphate

[Phosphoglucomutase]

---> Glucose 6-phosphate

 

Regulation of glycogen synthesis and breakdown

cAMP mechanism

Glucagon in liver
=> activates adenylyl cyclase (via Gs protein)
=> Increase in cAMP

Epinephrine in liver and muscles
=> activates adenylyl cyclase (via beta-2 receptor)
=> Increase in cAMP

Increase in cAMP

=> activates cAMP-dependent protein kinase

cAMP-dependent protein kinase
(? aka protein kinase)
* Activates phosphorylase kinase, and thus phosphorylase
* Inactivates glycogen synthase

Thus, glycogenolysis

Other effects of increased cAMP

... include

• Inhibits pyruvate kinase
• Indirectly inhibits phosphofructokinase
• Indirectly stimulates fructose 1,6-bisphosphatase

All of these effects inhibit glycolysis and encourage gluconeogenesis.

Glucose 6-phosphatase

In tissues other than liver, there is no glucose 6-phosphatase

Thus,
=> glucose 6-phosphate builts up
=> increased glucose catabolism
(via Embden-Meyerhof pathway and hexose monophosphate shunt)
=> increased lactate production

Glycogen synthase

Glycogen synthase converts glucose 1-phosphate to glycogen

Active: glycogen synthase a (dephosphorylated)

Inactive: glycogen synthase b (phosphorylated)

Opposite to phosphorylase and phosphorylase kinase

Phosphorylase and phosphorylase kinase

Phosphorylase kinase activates phosphorylase

Phosphorylase converts glycogen to glucose 1-phosphate

Active: phosphorylase a (phosphorylated)

Inactive: phosphorylase b (dephosphorylated)

Similarly,

Active: phosphorylase kinase a (phosphorylated)

Inactive: phosphorylase kinase b (dephosphorylated)

 

cAMP-independent mechanism

Epinephrine via alpha1 receptor
=> increase intracellular [Ca2+]
=> activates phosphorylase kinase

 

Overall effect

Glucagon
* act on liver
=> increased glucose

Epinephrine
* Act on liver and muscles
* via alpha1 receptor
--> Activate adenylyl cyclase
=> increased glucose and lactate level in blood