Regulation and control of glycogen metabolism

Question 1

Glycogen synthesis (anabolism) is done by which enzyme

Answer 1

Glycogen synthase

Question 2

Glycogen breakdown (catabolism) is done by which enzyme

Answer 2

Glycogen phosphorylase

Question 3

Glycogen synthase is subjected to two types of regulation:

Answer 3

1. Allosteric
2. Covalent
   -Dephosphorylated: form a, active
   -Phosphorylated: form b, low activity
   **CAREFUL!!!! Glycogen synthase is ACTIVATED by dephosphorylation

Question 4

Positive allosteric regulation of glycogen synthase

Answer 4

G6P and glucose induce a conformational change that will favour dephosphorylation

Question 5

Positive covalent regulation of glycogen synthase

Answer 5

1. Dephosphorylation catalyzed by phosphoprotein phosphatase-1 (PP1)
2. PP1 is activated in response to an increase in glycemia (high glucose, insulin).
3. The insulin pathway will induce the phosphorylation of the Glycogen targeting protein (GM), which in turn activates PP1

Question 6

Diagram of regulating glycogen synthase

Answer 6

Question 7

Insulin regulation of PP1 (Regulation of glycogen synthase)

Answer 7

Glycogen synthase and glycogen phosphorylase are all together with phosphorylase kinase (all 3 can be regulated by insulin and glucagon)
-Gm activated by insulin
-Gm activates PP1
-PPI activates glycogen synthase

Question 8

Negative Regulation of glycogen synthase (Covalent regulation: Glucagon regulation of PP1 and Inhibitor 1)

Answer 8

1. Phosphorylation of GM (second site) and Inhibitor-1 by Protein Kinase A (PKA).Leads to the inactivation of PP1.
2. PKA pathway is induced by the binding of glucagon and adrenaline (or epinephrine) to their receptors.

In image: Inhibitor 1 binds to PP1 and removes PP1, so it can not phosphorylate glycogen synthase

Question 9

Negative regulation of glycogen synthase through glycogen synthase kinase 3

Answer 9

1. Phosphorylation of glycogen synthase on three sites by glycogen synthase kinase 3 (GSK3).
   -Before this phosphorylation, glycogen synthase must be first “primed” by a phosphorylation by casein kinase II (CKII).
2. GSK3 activity is inhibited by the insulin pathway.

Question 9

Negative regulation of glycogen synthase through glycogen synthase kinase 3

Answer 9

1. Phosphorylation of glycogen synthase on three sites by glycogen synthase kinase 3 (GSK3).
   -Before this phosphorylation, glycogen synthase must be first “primed” by a phosphorylation by casein kinase II (CKII).
2. GSK3 activity is inhibited by the insulin pathway.

Question 10

Insulin Regulation of GSK3

Answer 10

** don’t memorize the image:

-Only know that GSK3 phosphorylates glycogen synthase 3x to make it inactive
-Insulin can phosphorylate GSK3 to make it inactive so then glycogen synthase becomes active

Question 11

Glycogen phosphorylase is subjected to two types of regulation

Answer 11

1. Allosteric
2. Covalent
   -Dephosphorylated: form b, less active
   -Phosphorylated: form a, active
   -Phosphorylation is achieved using the phosphorylase b kinase.

Question 12

Regulation of glycogen phosphorylase by the PKA pathway (glucagon and epinephrin)

Answer 12

Question 13

Allosteric Regulation of glycogen phosphorylase in muscle

Answer 13

Calcium released by working muscles and AMP accumulation from muscle contraction activate glycogen breakdown by stimulating Phosphorylase b phosphorylation.
-Ca2+ acts on the phosphorylase b kinase whereas AMP binds to the phosphorylase itself.
-ATP acts as an allosteric inhibitor by blocking the allosteric site to which AMP binds.

Question 14

Covalent Regulation of glycogen phosphorylase in muscle

Answer 14

Epinephrine, a hormonal fight or flight signal, stimulates glycogen breakdown in muscles by favouring Phosphorylase b phosphorylation through the PKA pathway.

Question 15

Regulation of glycogen phosphorylase in muscle

Answer 15

Calcium binds to kinase, and amp binds to the phosphorylase themselves

Question 16

Covalent Regulation of glycogen phosphorylase in liver (low glucose condition)

Answer 16

you want to stimulate glycogen breakdown:

Glucagon stimulates Phosphorylase b kinase to phosphorylate Phosphorylase b into Phosphorylase a, thereby activating glycogen breakdown.
-Phosphorylation of the phosphorylase b kinase is achieved via the PKA pathway.

Question 17

Allosteric Regulation of glycogen phosphorylase in liver (high glucose condition)

Answer 17

Glucose binding to allosteric sites inhibiting Phosphorylase a by exposing its phosphorylation site to PP1, thereby reducing glycogen breakdown in response to high availability of glucose

Question 18

Covalent Regulation of glycogen phosphorylase in liver (high glucose condition)

Answer 18

Release insulin because high glucose concentration:

Insulin stimulates PP1 to dephosphorylate Phosphorylase a into Phosphorylase b, thereby inhibiting glycogen breakdown.

In image: The step 2 wont happen in this image
-PP1 is major (master) switch and dephosphorylates all 3 enzymes (glycogen phosphorylase, phosphorylase kinase, and glycogen synthase

Question 19

Reciprocal regulation of glycogen metabolism

Answer 19