Last updated on January 11, 2020 at 12:11
- Both glycogen synthase and glycogen phosphorylase have two forms, one active and one inactive.
- The forms are interconvertible, and the only thing that differentiates them is phosphorylation.
- This phosphorylation is controlled by other enzymes, which in turn are controlled by other factors
- What’s most important from this topic is which factors regulate the two enzymes, in which way they regulate them and in which direction
- See the “regulation” page for this
The regulation of glycogen phosphorylase. Note that the we use the name protein phosphatase 1 instead of phosphorylase a phosphatase, and the name phosphorylase kinase instead of phosphorylase b kinase.
Regulation of glycogen phosphorylase
This enzyme has two forms, one active (a) form and one inactive (b) form. The enzyme is in its active form when it is phosphorylated and in its inactive form when dephosphorylated. Whether the enzyme glycogen phosphorylase is in the active or inactive form is determined by enzymes that either phosphorylate it or dephosphorylate it. The enzyme responsible for phosphorylation, and therefore activation, of glycogen phosphorylase is phosphorylase kinase. When phosphorylase kinase is activated, so is glycogen phosphorylase.
Glucagon and epinephrine are hormones that are the body’s signal of hunger; they are secreted when the body needs to break down its energy stores like glycogen and fat to increase the available energy and higher blood glucose. Both these hormones work by activating protein kinase A (PKA), a type of enzyme called a kinase which phosphorylates other proteins. PKA then activates phosphorylase kinase.
Protein phosphatase 1 (PP1) catalyses the dephosphorylation of glycogen phosphorylase, which inactivates it. PP1 is activated by insulin, the hormone that is secreted to lower the blood sugar level. When glycogen phosphorylase is active, we break down glycogen to produce glucose, which we obviously don’t want when we want to lower the blood sugar level. Therefore it makes sense that insulin should inactivate glycogen phosphorylase. In the liver, glycogen phosphorylase is also regulated allosterically by glucose, which inactivates it.
PP1 inactivates glycogen phosphorylase and also phosphorylase kinase. So PP1 inactivates glycogen phosphorylase directly by dephosphorylating it, but it also inactivates it indirectly by dephosphorylating phosphorylase kinase.
Glucose allosterically inhibits glycogen phosphorylase.
Regulation of glycogen synthase
Glycogen synthase also has two forms, one active (a) and one inactive (b) form. In contrast to glycogen phosphorylase however, the active form is the dephosphorylated while the inactive form is phosphorylated. That means that phosphorylation of glycogen synthase will deactivate it, and dephosphorylating will activate it.
The regulation of glycogen synthase. CKII is casein kinase II.
Glycogen synthase kinase 3 does what its name suggests, and phosphorylates GS to deactivate it. Insulin inhibits GSK3 activity. Insulin therefore activates GS, as it inhibits that which inhibits it.
A second kinase called casein kinase II also phosphorylates and inactivates glycogen synthase. A third kinase called AMPK also phosphorylates and inactivates glycogen synthase. AMPK is activates when the levels of AMP in the cell is high. AMPK is further detailed in a later topic.
PP1 does work on GS as well as glycogen phosphorylase. By removing the phosphates on GS, it activates it. PP1 is, in turn, activated by factors shown on the illustration to the right. PP1 is therefore the only regulator that directly regulates both GS and glycogen phosphorylase.
As seen on the illustration, glucose and glucose 6-phosphate both allosterically activate glycogen synthase.
3. Glycogen synthesis and degradation
5. Regulation and disorders of carbohydrate metabolism