L8- Regulation of Glycogen Metabolism

Question 1

LO1: List the enzymes that are required to completely disassemble glycogen into glucose (glycogenolysis) (3 enzymes)

glycogen phosphorylase
bifunctional enzyme-2 parts

Answer 1

1. glycogen phosphorylase: catalyzes rate-limiting step; phosphorolytic cleavage of alpha-1,4 glycosidic bbonds by adding inorganic phosphate to release glucose-1-P (ends of branch points/non-reducing ends)
2. alpha-1,4–>alpha-1,4 glucan transferase: cleaves one alpha-1,4 glycosidic bond and forms another, resulting in three glucose residues moving from one end of one chain to the end of another (makes chains less branched/phosphorylase can work better)
3. alpha-1,6 glucosidase: hydrolyzes single glucose unit at last branch point, releasing a free glucose

Question 2

LO2: How does cAMP coordinate glycogenolysis and glycogenesis?

Answer 2

cAMP=second messenger that activates protein kinases (by inhibiting protein phosphatase 1 (PP1)), leading to phosphorylation and activation of glycogen phosphorylase

      - cAMP levels increased by epinephrine binding to B-receptors in liver and muscle
       - cAMP levels increased by glucagon in liver

cAMP activates glycogen phosphorylase, leading to glycogenolysis
cAMP inhibits glycogenesis (by inhibiting glycogen synthase)

Question 3

LO3: What are the functional differences between muscle and liver phosphorylase?

Answer 3

Muscle vs. liver have isozymes of glycogen phosphorylase

      - muscle: AMP is an allosteric activator and indicates decreased energy status of cell
      - liver: glucose is an allosteric inhibitor and indicates the glucose status of the cell

Question 4

LO4: How does Ca+2 synchronize glycogen degradation and muscle contraction?

Answer 4

Glycogen degradation

1. Epinephrine binding to alpha1-receptors increases Ca+2
2. Ca+2 (along with cAMP) acts as a second messenger to activate protein kinases and therefore activate glycogen phosphorylase through phosphorylation

Muscle contraction
3. Ca+2 dependent mechanism in neurons synchronizes muscle contraction with glycogenolysis (via allosteric activation of a phosphorylase kinase)

Question 5

LO5: How does ephinephrine affect glycogenolysis when it binds to B-receptors vs. Alpha1 receptors? In liver vs. muscle?

Answer 5

MUSCLE-activates glycogen phosphorylase
B-receptor activation: increases cAMP, which activates protein kinases
Alpha1-receptor activation: increases Ca+2, which leads to phosphorylation of glycogen phosphorylase

LIVER-activates glycogen phosphorylase
B-receptor activation: increases cAMP, which activates protein kinases
Alpha-1 receptor activation: mediated by IP3 and Ca+2, which activate glyccogen phosphorylase

Question 6

LO6: Compare/contrast the hormonal mechanisms that operate in muscle vs. liver to coordinate glycogenesis and glycogenolysis

Answer 6

MUSCLE

• epinephrine binds to B-adrenergic receptors to increase cAMP, and to alpha1-adrenergic receptors to increase Ca+2
• insulin activates degradation of cAMP

LIVER

• glucagon binds to its receptor to increase cAMP
• epinephrine binds to B-adrenergic receptors to increase cAMP
• epinephrine binding to alpha1-adrenergic receptors mediates IP3 and Ca+2
• insulin activates degradation of cAMP

Question 7

LO6: What enzyme effects are seen (and what effects on glucose occur) in response to increased insulin vs. increased glucagon vs. increased epinephrine?

Answer 7

INSULIN-blood glucose decreases

• increased protein phosphatase
• decreased glucose-6-pase
• increased glucokinase
• increased glycogen synthase

GLUCAGON-increased blood glucose
-increased adenylate cyclase (catalyzes ATP to cAMP and pyrophosphate)

EPINEPHRINE-increased blood glucose
-increased adenylate cyclase (catalyzes ATP to cAMP and pyrophosphate)

Question 8

LO7: What would the consequences of a deficiency in glucose-6-phosphatase be on glycogen stores in liver vs. muscle?

Answer 8

glucose-6-phosphatase: hydrolyzes glucose-6-phosphate to release glucose and a phosphate group

• highly expressed in liver, kidney, and pancreas (and sometimes intestinal mucosa)–>glycogen stores can be used to increase blood glucose
• not highly expressed in muscle–>glycogen stores in muscle cannot be released to increase blood glucose

DEFICIENCY: would only affect use of glycogen stores from liver; glucose would stay trapped in kidney/liver and hypoglycemia would occur (von Gierke’s disease)

Question 9

LO8/LO9: What would the consequences of a deficiency in glycogen phosphorylase be in liver vs. muscle?

Answer 9

glycogen phosphorylase: catalyzes rate-limiting step in glycogenolysis (cleaves ends of branch points of glycogen)

DEFICIENCY-McArdle’s disease vs. Her’s disease
muscle- glycogen breakdown wouldn’t occur and muscle wouldn’t be able to draw from glycogen stores when needed (exercise, starvation etc)

liver-glycogen breakdown wouldn’t occur and liver wouldn’t be able to maintain homeostasis of blood glucose

Question 10

LO9: Symptoms/treatment of McArdle’s disease (Type V Storage Disease)

Answer 10

Symptoms: muscle weakness, muscle cramps during exercise, failure of plasma lactate to increase during exercise, excessive muscle glycogen stores

Treatment: limit strenuous exercise to minimize effects on kidney (muscle damage occurs easily), but light exercise can improve tolerance for exercise