Metabolic Regulation by Hormones

What are the 3 main hormones emphasized in these slides for metabolic regulation?

Insulin, glucagon, and adrenaline (epinephrine).

What is insulin and what is its overall effect on blood glucose?

Insulin is a peptide hormone produced by pancreatic beta cells that lowers blood glucose.

What is glucagon and what is its overall effect on blood glucose?

Glucagon is a peptide hormone produced by pancreatic alpha cells that raises blood glucose.

What is adrenaline (epinephrine) and what is its overall metabolic effect?

Adrenaline is a hormone released from the adrenal gland in response to the sympathetic nervous system that promotes rapid fuel mobilization, including glycogen and lipid breakdown.

What kind of receptor is used by adrenaline in these slides?

A G-protein-coupled receptor (GPCR).

What second messenger is produced after adrenaline or glucagon activates its receptor?

cAMP.

What enzyme makes cAMP in the hormone signaling cascade?

Adenylyl cyclase.

What kinase is activated by cAMP?

Protein kinase A (PKA).

What is the classic signaling sequence for adrenaline or glucagon in these slides?

Hormone binds receptor -> G protein activated -> adenylyl cyclase activated -> cAMP increases -> PKA activated.

What does PKA do to glycogen phosphorylase kinase?

PKA phosphorylates and activates glycogen phosphorylase kinase.

What does glycogen phosphorylase kinase do to glycogen phosphorylase?

It phosphorylates glycogen phosphorylase b to form glycogen phosphorylase a, the active form.

Which form of glycogen phosphorylase is active?

Glycogen phosphorylase a.

Which form of glycogen phosphorylase is less active or inactive?

Glycogen phosphorylase b.

What is the net effect of adrenaline or glucagon on glycogen phosphorylase?

They promote phosphorylation and activation of glycogen phosphorylase, increasing glycogenolysis.

What product is generated directly by glycogen phosphorylase during glycogenolysis?

Glucose-1-phosphate.

What happens to glycogen synthase when PKA is activated?

PKA phosphorylates glycogen synthase and inactivates it, inhibiting glycogenesis.

Which form of glycogen synthase is active?

Glycogen synthase a.

Which form of glycogen synthase is inactive?

Glycogen synthase b.

What is the overall effect of adrenaline and glucagon on glycogen metabolism?

They stimulate glycogen breakdown and inhibit glycogen synthesis.

What phosphatase is stimulated by insulin in these slides?

Protein phosphatase 1 (PP1).

What does PP1 do to glycogen phosphorylase a?

It dephosphorylates glycogen phosphorylase a to glycogen phosphorylase b, reducing glycogenolysis.

What is the effect of insulin on glycogenolysis?

Insulin inhibits glycogenolysis.

How does glucose itself help inhibit glycogenolysis in the liver slides?

Glucose allosterically changes glycogen phosphorylase a so it is more easily dephosphorylated by PP1, reducing activity.

What is the effect of insulin on glycogen synthase?

Insulin promotes dephosphorylation and activation of glycogen synthase, favoring glycogenesis.

What is the overall effect of insulin on glycogen metabolism?

It inhibits glycogen breakdown and promotes glycogen synthesis.

What is the difference between the major outcomes of glycogen breakdown in muscle versus liver?

In muscle, glucose from glycogen is used for glycolysis and ATP production; in liver, glucose is released into the blood to raise blood glucose.

What is a major feature of the glucagon/adrenaline cascade shown on the slide?

Large signal amplification.

According to the slide, one hormone molecule can ultimately yield about how many glucose molecules?

About 10,000 glucose molecules.

Which hormone is emphasized as acting in hepatocytes to raise blood glucose?

Glucagon.

Which hormone is emphasized as acting very rapidly during sympathetic stress responses?

Adrenaline (epinephrine).

When blood glucose is high, what happens to insulin?

Insulin increases.

When blood glucose is low, what happens to glucagon?

Glucagon increases.

In the liver, high blood glucose and insulin tend to favor what 3 broad processes?

Increased glycogen synthesis, decreased glycogen breakdown, and increased glycolysis.

In the liver, low blood glucose and glucagon tend to favor what 3 broad processes?

Increased glycogen breakdown, decreased glycogen synthesis, and decreased glycolysis.

How does low blood glucose affect cAMP and PKA in the liver?

Low blood glucose increases glucagon, which increases cAMP and activates PKA.

How does high blood glucose affect the glucagon-cAMP-PKA pathway in the liver?

High blood glucose increases insulin and suppresses the glucagon/cAMP/PKA pathway.

What is Type I glycogen storage disease (von Gierke) due to according to the slide?

Glucose-6-phosphatase deficiency.

What tissue is primarily affected in Type I glycogen storage disease (von Gierke) according to the slide?

Liver.

What is Type II glycogen storage disease (Pompe) due to according to the slide?

Lysosomal glucosidase deficiency.

What tissues are primarily affected in Pompe disease according to the slide?

Skeletal and cardiac muscle.

What is Type IIIa glycogen storage disease (Cori or Forbes) due to according to the slide?

Debranching enzyme deficiency.

What is Type IV glycogen storage disease (Andersen) due to according to the slide?

Branching enzyme deficiency.

What is Type V glycogen storage disease (McArdle) due to according to the slide?

Muscle phosphorylase deficiency.

What is a classic symptom of McArdle disease on the slide?

Exercise-induced cramps and pain with myoglobin in urine.

What is Type VI glycogen storage disease (Hers) due to according to the slide?

Liver phosphorylase deficiency.

What is Type VII glycogen storage disease (Tarui) due to according to the slide?

Muscle PFK-1 deficiency.

What additional finding is noted for Tarui disease on the slide besides exercise symptoms?

Hemolytic anemia.

What glycogen storage disease on the slide is associated with GLUT2 deficiency?

Type XI (Fanconi-Bickel).

What enzyme activity state should you know from these slides regarding phosphorylation?

Some enzymes are activated by phosphorylation while others are inactivated, especially glycogen phosphorylase being activated and glycogen synthase being inactivated by phosphorylation.

What is the high-yield phosphorylation rule for glycogen phosphorylase in these slides?

Phosphorylation activates glycogen phosphorylase.

What is the high-yield phosphorylation rule for glycogen synthase in these slides?

Phosphorylation inactivates glycogen synthase.