LECTURE 27 - HORMONAL REGULATION OF METABOLISM

Question 1

Explain the signal transduction mechanism of glucagon

Answer 1

• Released upon a drop in blood glucose levels
• Binds to a G-protein-coupled receptor (glucagon receptor), which activates GS (adenylate cyclase stimulator)
• Raises the concentration of glucose and fat in the bloodstream

Question 2

Explain the signal transduction mechanism of insulin

Answer 2

• Released upon the raise in blood glucose levels
• Binds to a receptor tyrosine kinase (insulin receptor)
• Promotes glucose uptake, glycogen synthesis, glycolysis, and fatty acid synthesis
• Ultimately, reduces the concentration of glucose in the bloodstream

Question 3

Describe the role of fructose 2,6-bisphosphate in regulation of glycolysis and gluconeogenesis

Answer 3

fructose 2,6-bisphosphate
– An allosteric effector
– Activates 6-phosphofructo-1-kinase
– Suppresses fructose 1,6-bisphosphatase

Fructose 2,6-bisphosphate increases glycolysis and suppresses gluconeogenesis

Question 4

Identify the catalytic activity of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase in liver

Answer 4

• Phosphorylation by protein kinase A switches the enzyme from a kinase to a phosphatase
• Decreases fructose 2,6-P2 levels
  – Fructose 2,6-bisphosphate increases glycolysis and suppresses gluconeogenesis
• Upon the release of glucagon or epinephrine, liver releases glucose to the bloodstream

Question 5

Identify the catalytic activity of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase in heart

Answer 5

• Phosphorylation by protein kinase A switches the enzyme from a phosphatase to kinase.
• Epinephrine increases fructose 2,6-bisphosphate, which stimulates glycolysis

Question 6

Explain the action of protein kinase A on the activity of pyruvate kinase and the consequence in the glycolysis

Answer 6

• Protein kinase A inactivates pyruvate kinase
• Phosphoenolpyruvate is not converted to pyruvate but used for gluconeogenesis

Decrease in glycolysis

Question 7

Identify genes induced by the action of glucagon

Answer 7

PEP carboxykinase, fructose 1,6-bisphosphatase, glucose 6-phosphatase

Question 8

Identify genes suppressed by the action of glucagon

Answer 8

glucokinase, 6-phosphofructo-1-kinase, and pyruvate kinase

Question 9

Explain the effects of glucagon on the glycogen metabolism

Answer 9

• Glucagon and epinephrine stimulate glycogen breakdown in liver
• By phosphorylation, protein kinase A activates glycogen phosphorylase and inactivates glycogen synthase
  – Activated glycogen phosphorylase breaks down glycogen to glucose-1-phosphate

Question 10

Explain the effects of glucagon on the lipid metabolism

Answer 10

Glucagon promotes fatty acid oxidation.
- Increases in triacylglycerol breakdown by phosphorylation of hormone-sensitive lipase.
- Suppresses acetyl-CoA carboxylase by phosphorylation

Question 11

Explain how insulin opposes the actions of glucagon and epinephrine in the liver

Answer 11

• Activates cAMP phosphodiesterase, which lowers cAMP levels
• Activates phosphoprotein phosphatase, which reverses the action of protein kinase A
• Activates acetyl CoA carboxylase by dephosphorylating the enzyme

Question 12

Describe the Warburg effect in cancer cells

Answer 12

Even when O2 is plentiful, cancer cells convert glucose to lactate

Question 13

Explain the activation mechanism of protein kinase A by cyclic AMP

Answer 13

1. 2nd messenger cAMP binds to the regulatory subunits of Protein Kinase A
2. Causes a conformational change that releases the inactive catalytic subunits
3. The released catalytic subunits are now active and able to phosphorylate target proteins