Lecture 23 - Glycogen Metabolism II

Question 1

What are the enzymes that regulate glycogen synthesis and how are they regulated?

L23 S4

Answer 1

Glycogen synthase:

• active, non-phosphorylated “a” form
• inactive, phosphorylated “b” form
• regulated by glycogen synthase kinase which response to insulin and PKA
• glucose-6-phosphate allosterically activates by stabilizing the active form

Glycogen phosphorylase:

• active, relaxed favored “a” form (default in liver)
• inactive, tense favored “b” form (default in muscle)
• regulated by allosteric effectors and phosphorylation (activation)

Question 2

Differentiate between liver and muscle glycogen phosphorylase.

L23 S8

Answer 2

Products of different genes.

Liver is inactivated by free glucose and is not affected by AMP.

Muscle is activated by AMP and inhibited by glucose-6-phosphate and ATP.

Mutation of liver GP causes Hers disease and mutation of muscle GP causes McArdle disease

Question 3

What is the effect of insulin and what proteins does it regulate?

L23 S13

Answer 3

Recognized by a RTK

Regulates:

• GLUT 4, moved to membrane
• protein kinase B (PKB), phosphorylates PP1 (activating) and GSK3 (inactivating)
• protein phosphatase 1 (PP1), dephosphorylates glycogen synthase (activates) and dephosphorylates glycogen phosphorylase (inactivated)
• glycogen synthase kinase (GSK3)

Effect:
-glycogen production via activation of glycogen synthase and inactivation of glycogen phosphorylase

Question 4

What is the type of receptor for glucagon, what proteins does it regulate, and what is its effect

L23 S19

Answer 4

Recognized by a GPCR (only present in liver

Regulates:
-protein kinase A (PKA), phosphorylates glycogen synthase (inactivates), PK (activates), and PP1 inhibitor (inhibits PP1)

Effect:
-glycogen breakdown via inactivation of glycogen synthase and activation of glycogen phosphorylase

Question 5

What is the type of receptor for epinephrine, what proteins does it regulate, and what is its effect

L23 S20

Answer 5

Recognized by GPCR (liver and muscle)

Effect:
-promotes glycogen breakdown

Question 6

What happens to glucose-1-phosphate in the liver and muscle?

L23 S23

Answer 6

Liver:
-converted to glucose-6-phosphate then glucose-6-phosphatase converts it to glucose which is released to the blood

Muscle:
-lacks glucose-6-phosphatase so glucose-6-phosphate remains trapped in the cell

Question 7

What is glycogen storage disorder 0 and what organ does it primarily effect?

L23 S28

Answer 7

Deficiency in glycogen synthase resulting in inability to produce glycogen.

Question 8

What is glycogen storage disorder I/Von Gierke and what organ does it primarily effect?

L23 S27

Answer 8

Glucose-6-phosphase deficiency resulting in increase amount of glycogen with normal structure.

Liver and kidney affected.

Question 9

What is glycogen storage disorder II/Pompe and what organ does it primarily effect?

L23 S27;32

Answer 9

α-1,4-glucosidase (lysosomal) deficiency resulting in a massive increase in glycogen with normal structure.

All organs affected

Question 10

What is glycogen storage disorder III/Cori and what organ does it primarily effect?

L23 S27-28

Answer 10

α-1,6-glucosidase deficiency resulting in increased glycogen with short outer branches.

Muscle and liver affected.

Question 11

What is glycogen storage disorder IV/Anderson and what organ does it primarily effect?

L23 S27;29

Answer 11

Branching enzyme (glucosyl 4:6 transferase) deficiency resulting in a normal amount of glycogen with long outer branches.

Liver and spleen affected.

Question 12

What is glycogen storage disorder V/McArdle and what organ does it primarily effect?

L23 S27;30

Answer 12

Muscle glycogen phosphorylase deficiency resulting in increased amount of normal glycogen.

Muscle affected.

Question 13

What is glycogen storage disorder VI/Hers and what organ does it primarily effect?

L23 S27;31

Answer 13

Liver glycogen phosphorylase deficiency resulting increase amount of normal glycogen.

Liver affected.