Topic 9: Glycogen Metabolism

Question 1

Where is most of the glycogen in the body stored?

Answer 1

Skeletal Muscle and Liver.

Question 2

What does Glycogenin do?

Answer 2

It starts new glycogen molecules.

The glycogen enzymes themselves are poor starters but good at adding on.

Question 3

What is Step 1 of glycogenesis?

Answer 3

Glucose is phosphorylated to Glucose-6-Phosphate by hexokinase/glucokinase.

ATP is used here.

Question 4

What is Step 2 of Glycogenesis?

Answer 4

Glucose-6-Phosphate is rearranged to Glucose-1-Phosphate by Phosphoglucomutase.

Question 5

What is Step 3 of Glycogenesis?

Answer 5

UTP comes together with Glucose-1-Phosphate by UDP-Glucose Pyrophosphorylase to make UDP-Glucose.

This is what Drives Glycogenesis. It is IRREVERSIBLE.

Pyrophosphate is generated.

Question 6

What is Step 4 of Glycogenesis?

Answer 6

UDP-Glucose via Glycogen Synthase is added Pre-existing glycogen molecule (primer) while UDP is removed.

Question 7

How are branches made in glycogen?

Answer 7

Every 10 residues 4:6 Transferase (branching enzyme) will create another branch by breaking a a-1,4 bond and creating a a-1,6 branch.

Question 8

What is Step 1 of GlycogenoLYSIS?

Answer 8

Glucose Molecule is removed from glycogen via Glycogen Phosphorylase and a Phosphate is added to make Glucose-1-Phosphate.

Pi is added here.

Glycogen Phosphorylase requires Pyridoxine/B6.

Question 9

What is Step 2 of Glycogenolysis?

Answer 9

Glucose-1-Phosphate is rearranged to Glucose-6-Phosphate via phosphoglucomutase.

Question 10

What is Step 3 of Glycogenolysis?

Answer 10

Glucose-6-Phosphate via Glucose-6-Phosphatase (gluconeogenic tissues only) is converted to Glucose. Final Step!

Free Pi is generated here.

Question 11

How is the a-1,6 bonded branching glucose removed?

Answer 11

Once a limit is reached, 4:4 transferase (de-branching enzyme) removes remaining glucose residues.

alpha-1,6-glucosidase removes a pure Glucose molecule.

about 10% of glycogen comes off as just Glucose (as opposed to Glucose-1-Phosphate)

Question 12

What happens if lysosomes are Glucosidase deficient?

Answer 12

Lysosome can take in glycogen but cannot break it down.

They get bigger and bigger –> organomegaly

Question 13

What two enzymes are regulated in glycogen metabolism?

Answer 13

GLYCOGEN SYNTHASE - buildup

GLYCOGEN PHOSPHORYLASE - breakdown

Question 14

How does phosphorylation affect Glycogen Synthase?

Answer 14

Glycogen Synthase + Phosphate = OFF

opposite of Phosphorylase

Question 15

How does phosphorylation affect Glycogen Phosphorylase?

Answer 15

Glycogen Phosphorylase + Phosphate = ON

opposite of Synthase

Question 16

What up-regulates glycogen synthesis/glycogenesis?

Answer 16

Insulin: Activates Phosphodiesterase to break cAMP into AMP, preventing the cascade from activating Glycogen Phosphorylase

Question 17

What up-regulates glycogen breakdown/glycogenolysis in the LIVER? (Note: Both liver and muscle do both methods but each tissue prefers one)

Answer 17

Epinephrine and Glucagon: Activate G-Protein –> cAMP –> activated Protein Kinase A –> activates Phosphorylase Kinase by phosphorylation –> THIS activates Glycogen Phosphorylase by phosphorylation

Phosphorylase Kinase inactivates Glycogen Synthase by phosphorylating it as well.

Question 18

What up-regulates glycogen breakdown/glycogenolysis in MUSCLE? (Note: Both liver and muscle do both methods but each tissue prefers one)

Answer 18

Hormone or Neurotransmitter activate Ca++ release –> Ca++ binds to Phosphorylase Kinase, activating it –> Activates Glycogen Phosphorylase by phosphorylating it

Ca++ also Binds to Calmodulin Protein Kinase, activating it –> Ca++-Calmodulin Protein Kinase phosphorylates Glycogen Synthase, deactivating it.

Question 19

What kind of receptor is insulin receptor and what does it do to glycogen metabolism?

Answer 19

Tyrosine kinase receptor. Stimulates glycogen synthesis.

Question 20

What kind of receptor is glucagon receptor and what does it do to glycogen metabolism?

Answer 20

cAMP receptor (G-Protein). Stimulates glycogen degradation.

Question 21

What kind receptor is epinephrine receptor and what does it do to glycogen metabolism?

Answer 21

Multiple types: adrenergic receptors:
ß - Liver and Muscle by way of cAMP
alpha- Liver and Muscle by way of Ca++ and IP3 (Phospholipase C)

Question 22

How does the ANS influence glucose homeostasis when blood glucose is LOW?

Answer 22

Ventromedial nucleus –> SYMPATHETIC signal to Liver, Gut, Pancreas (alpha-cells for glucagon), adipose, heart ==> glycogen BREAKDOWN

Question 23

How does the ANS influence glucose homeostasis when blood glucose is HIGH?

Answer 23

Lateral Nuclei –> PSNS Vagus Nerve signal to ß-cells for insulin ==> glycogen SYNTHESIS

Question 24

What is Type 1 Glycogen Storage Disease?

Answer 24

von Gierke’s Disease: Glucose-6-Phosphatase deficiency –> cannot finish glycogenolysis or gluconeogenesis, builds up inside the cells

Heptomegaly, Hypoglycemia, Lactate Acidosis

Beagles, Maltese, Toy breeds

Question 25

What is Type 2 Glycogen Storage Disease?

Answer 25

Pompe’s Disease: Lysosomal Storage Disease: alpha-Glucosidase Deficiency –> buildup of glycogen inside lysosomes

Liver and Heart Failure

Dogs, Cats, Cattle, Sheep, Whales, and Turkeys

Question 26

What is Type 3 Glycogen Storage Disease?

Answer 26

Cori’s Disease: deficiency in De-branching enzyme (4:4 transferase) glycogen molecules continue to grow and grow, can add branches but not remove them.

Hepatomegaly

German Shepherds, Akitas, Curly Retrievers, Toy breeds

Question 27

What is Type 4 Glycogen Storage Disease?

Answer 27

Andersen’s Disease: deficiency in branching enzyme (4:6 transferase) can elongate the chains but no longer compact, can still break down but ABnormal structure of glycogen

Cirrhosis (scarring) of Liver and Muscle

Norwegian Forest Cats

Question 28

What is Type 5 Glycogen Storage Disease?

Answer 28

McArdle’s Disease: deficiency in MUSCLE Phosphorylase: muscles can bulidup glycogen but NOT break it down; intracellular glucose is limited

Exercise intolerance; fatigue quickly, cramp up quickly (need ATP for myosin head release), rhabdomyolysis (muscle breakdown)

Sheep, Charolais Cattle

Question 29

What is Type 6 Glycogen Storage Disease?

Answer 29

Hers Disease: deficiency in liver phosphorylase: cannot breakdown glycogen

Hepatomegaly, Hypoglycemia

Question 30

What is Type 7 Glycogen Storage Disease?

Answer 30

Tarui’s Disease: muscle PFK deficiency–> glycolysis is compromised in muscle –> glycogen tends to accumulate

Exercise intolerance, Increased muscle cell size, rhabdomyolysis

English Springer, American Cocker, Cats

Question 31

What is Type 9 Glycogen Storage Disease?

Answer 31

Liver Phosphorylase Kinase deficiency–> cannot turn on Phosphorylase –> accumulated glycogen

Hepatomegaly; Hypoglycemia

Question 32

What is Type O Glycogen Storage Disease?

Answer 32

Glycogen Synthase Deficiency–> cannot make glycogen

Fasting hypoglycemia, post-prandial hyperglycemia (can’t put glucose into glycogen), Quick to fatigue

Question 33

What Vitamin is essential for proper functioning of Glycogen Phosphorylase? What kind of effects would expect from a deficiency?

Answer 33

Vitamin B6/Pyridoxine

Hypoglycemia, Hepatomegaly, Exercise Intolerance, quick to fatigue