Glycogenolysis Regulation

Question 1

Describ glycogen usage in the liver

Answer 1

• Broken down to maintain blood glucose during exercise or fasting.
• Liver has glucose-6-phosphatase→Can therefore turn G 6-P into glucose.

Question 2

Describe glycogen usage in muscle

Answer 2

• Glycogen is broken down to provide substrate for anaerobic glycolysis.
• G 6-P is broken down anaerobically but cant be turned back into glucose
• Muscle glycogen cannot contribute to blood glucose as muscle lacks glucose 6-phosphatase enzyme .

–G 6-P is “trapped” in cells.

Question 3

Describe glycogenolysis regulation

Answer 3

• Regulated by glycogen phosphorylase which in turn is regulated by a kinase.
• Happens in response to many factors including the energy state of the cell and hormones.

–Insulin, adrenalin (epinephrine) and glucagon

Question 4

Describe allosteric regulation of Glycogen Phosphorylase in the liver

Answer 4

•Liver – default is phosphorylase a (active).

–Role is to maintain blood glucose levels.

–Therefore signalling is needed to turn this off.

–Inactivated by glucose.

Question 5

Describe allosteric regulation of Glycogen Phosphorylase muscle

Answer 5

•Muscle – default is phosphorylase b (inactive).

–Should only be active during muscle contraction.

–Therefore signalling is needed to turn this on.

–Activated by AMP (indicates energy poor is concentration is high), inhibited by ATP.

Question 6

Describe hormonal regulation of Glycogen Phosphorylase

Answer 6

•Hormones trigger conversion of phosphorylase b to phosphorylase a.

Epinephrine is released from adrenal glands (energy).

• Mainly muscle.

Glucagon released from pancreatic alpha cells (low blood glucose).

• Mainly liver.

Question 7

Hormonal Regulation of Glycogen Phosphorylase: How is it turned off?

Answer 7

•Turned off by:

–Dephosphorylation of phosphorylase a to phosphorylase b by protein phosphatase 1.

–Absence of activated kinase to phosphorylate phosphorylase b to phosphorylase a.

•Remember:

–Phosphorylase a is active.

–Phosphorylase b is inactive.

Question 8

What is the function of Protein Phosphatase 1 (PP1)

Answer 8

• Removes phosphate groups from activated proteins.
• Converts phosphorylase a to phosphorylase b.
• Insulin activates protein phosphatase 1.

Question 9

Describe the properties of Phosphorylase Kinase

Answer 9

• Activated by calcium in muscle.
• 4 subunits (α,β,γ,δ)
• δ subunit is calmodulin (Ca²⁺ sensor).
• Ca²⁺ released by muscle contraction therefore stimulates glycogen breakdown.

PKA phosphorylates phosphorylase kinase to a partially active form and so does Ca^2+. The fully active form requires both.

Question 10

Glycogenolysis regulation:

What is it turned on by?

Answer 10

–Increased AMP, decreased ATP.

–Increased intracellular Ca²⁺. When muscle contraction occurs, glycogen can be broken down to form glucose.

–Elevated blood glucagon→When low blood glucose, you can generate more glucose from glycogen

–Elevated blood adrenalin (in the fight or flight response)) (epinephrine).

Question 11

What is glycogenesis?

Answer 11

• Formation of glycogen from glucose-6-phosphate. (G 6-P)
• Cellular glucose converted to G 6-P by hexokinase.
• 5 step process.
• Final step is activity of a branching enzyme to form a-1,6-linkages.

UTP – uridine triphosphate.

PPi – pyrophosphate.

Question 12

UDP Glucose and Glycogen

Answer 12

An α-1.4- linkage is formed between the new glucose and the glyogen chain

Question 13

Branching

Answer 13

• Branching amplifies the number of glucose that can be degrade from glycogen in one go
• Branching also makes it less soluble
• Branching keeps the molecule more compact for storage

Question 14

Describe Glycogenesis Regulation

Answer 14

• Occurs at the level of glycogen synthase.
• Two forms:

–a is active and non-phosphorylated.

–b is inactive and phosphorylated.

Question 15

Glycogenesis Regulation: What does insulin cause?

Answer 15

Dephosphorylation

1. Insulin signals via its receptor (tyrosine kinase)
2. Autophosphorylation occurs
3. IRS-1 is phosphoylated
4. PI-3 kinase (PI-3K) is recruited
5. A further signalling cascade through kinases leads to the phosphoylation of GSK3 (glycogen sythase kinase 3)
6. GSK3 normally phorphorylates glycogen syntahse a (active) to glycogen synthase b (active)
7. Insulin phosphorylates GSK3 so more active glyogen synthase is produced therefore more glycogen is produced
8. Protein phosphatase 1 (PP1) can reactivate the enzyme glycogen synthase a

Question 16

Describe the effect of Insulin on glycogen synthase

Answer 16

• Insulin activates its receptor.
• IRS1 is phosphorylated on Tyr.
• Phosphatidyl-inositol-3-kinase (PI-3K) is activated.
• Protein kinase B (PKB) is activated.
• Glycogen synthase kinase 3 (GSK-3) is inhibited.
• Glycogen synthase dephosphorylated by protein phosphatase 1 (PP1).

Question 17

Glycogen synthesis is turned on by:

Answer 17

•Insulin-dependent dephosphorylation of glycogen synthase.

–Glycogen synthase kinase 3 inhibited.

–Protein phosphatase 1 activated.

Question 18

How is glycogen synthesis turned off?

Answer 18

• Protein kinase A phosphorylates and inhibits glycogen synthase
• Protein phosphatase 1 is inactivated by protein kinase A so glycogen synthase remains phosphorylated.

Question 19

Produce a summary table

Answer 19