Regulation of glycogen metabolism in muscle and liver (9)

What are the 3 hormone receptors involved in glycogen control?

1. Receptor Tyrosine Kinase

2. β-adrenergic GPCR

3. α-adrenergic GPCR

What does the RTK regulate?

Insulin

What are the events of insulin regulation?

1. Binding of insulin

2. Dimerization

3. Transphosphorylation

Upon transphosphorylation, what are the downstream events of insulin binding?

1. PKA active

2. GSK phos.= inactive

3. No GS phos = active

4. PP1 : dephosphorylates any phos. GS

What do the β-adrenergic GPCRs regulate?

Epinephrine (muscle) or glucagon (liver)

What downstream events does the GTP-bound G_αs activate?

1. Adenylate cyclase

2. AC produces cAMP

3. cAMP activates PKA, etc.

What do the α-adrenergic GPCRs regulate?

Epinephrine and glucagon in the liver

What downstream events does the GTP-bound G_αq activate?

1. Binding of ligand

2. Activation of phospholipase C: hydrolysis of PIP₂ into IP₃ + DAG

3. Release of Ca²⁺ through IP₃

4. Activation of PKC by DAG

What events activate glycogen degradation in the MUSCLE? (2)

1. Adrenaline on -receptors from stress

2. Ca²⁺ from muscle contraction

What are the events of PKA activation ?

1. GS inhibition

2. PK activation

3. Glycogen breakdown ON

What events activate glycogen synthase in the MUSCLE? (2)

1. High blood glucose (GLUT4)

2. High insulin (RTK)

How does insulin affect GSK3β?

Inhibits it

How does the insulin-bound RTK affect the bicyclic cascade?

Activation of PP1 = dephos. of GS (↑) and PK(↓)

How do liver cells respond to stress?

Glycogen breakdown from binding of epinephrine on α and β adrenergic receptors

How do α-adrenergic receptors affect the cascade?

DAG-activated PKC inhibits GS

How do the β-adrenergic receptors affect the cascade?

cAMP activates PKA = release of glucose through GLUT2

How do liver cells respond to low blood glucose?

cAMP activates PKA = release of glucose through GLUT2

Type I glycogen storage deficiency

von Gierke’s disease or G6Pase deficiency

When is G6Pase needed?

G1P→G6P→Glc in bloodstream

What does this first deficiency lead to?

Increase in contraction of G6P which activates GS

What are the symptoms of von Gierke’s disease?

1. Massive liver

2. Hypoglycemia

What is the treatment for von Gierke’s disease?

Portal vein to permit glucose rich blood to reach peripheral tissues before the liver

Type V glycogen storage disease

McArdle’s disease or muscle phosphorylase deficiency

What does this second disease lead to?

No glycogen breakdown in muscle = no fuel for glycolysis

What is the symptom of this second disease?

Painful cramps during exercise

What is the ‘‘treatment’’ for this second disease?

1. ADP levels rise as the workout goes on = vasodilation = fresh supply of glucose and fatty acids

2. Liver phosphorylase

Type IV glycogen storage disease

Her’s disease or liver phosphorylase deficiency

What is the symptom of this third disease?

Hypoglycemia