Topic 9: Glycogen Metabolism Flashcards
Where is most of the glycogen in the body stored?
Skeletal Muscle and Liver.
What does Glycogenin do?
It starts new glycogen molecules.
The glycogen enzymes themselves are poor starters but good at adding on.
What is Step 1 of glycogenesis?
Glucose is phosphorylated to Glucose-6-Phosphate by hexokinase/glucokinase.
ATP is used here.
What is Step 2 of Glycogenesis?
Glucose-6-Phosphate is rearranged to Glucose-1-Phosphate by Phosphoglucomutase.
What is Step 3 of Glycogenesis?
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.
What is Step 4 of Glycogenesis?
UDP-Glucose via Glycogen Synthase is added Pre-existing glycogen molecule (primer) while UDP is removed.
How are branches made in glycogen?
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.
What is Step 1 of GlycogenoLYSIS?
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.
What is Step 2 of Glycogenolysis?
Glucose-1-Phosphate is rearranged to Glucose-6-Phosphate via phosphoglucomutase.
What is Step 3 of Glycogenolysis?
Glucose-6-Phosphate via Glucose-6-Phosphatase (gluconeogenic tissues only) is converted to Glucose. Final Step!
Free Pi is generated here.
How is the a-1,6 bonded branching glucose removed?
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)
What happens if lysosomes are Glucosidase deficient?
Lysosome can take in glycogen but cannot break it down.
They get bigger and bigger –> organomegaly
What two enzymes are regulated in glycogen metabolism?
GLYCOGEN SYNTHASE - buildup
GLYCOGEN PHOSPHORYLASE - breakdown
How does phosphorylation affect Glycogen Synthase?
Glycogen Synthase + Phosphate = OFF
opposite of Phosphorylase
How does phosphorylation affect Glycogen Phosphorylase?
Glycogen Phosphorylase + Phosphate = ON
opposite of Synthase
What up-regulates glycogen synthesis/glycogenesis?
Insulin: Activates Phosphodiesterase to break cAMP into AMP, preventing the cascade from activating Glycogen Phosphorylase
What up-regulates glycogen breakdown/glycogenolysis in the LIVER? (Note: Both liver and muscle do both methods but each tissue prefers one)
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.
What up-regulates glycogen breakdown/glycogenolysis in MUSCLE? (Note: Both liver and muscle do both methods but each tissue prefers one)
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.
What kind of receptor is insulin receptor and what does it do to glycogen metabolism?
Tyrosine kinase receptor. Stimulates glycogen synthesis.
What kind of receptor is glucagon receptor and what does it do to glycogen metabolism?
cAMP receptor (G-Protein). Stimulates glycogen degradation.
What kind receptor is epinephrine receptor and what does it do to glycogen metabolism?
Multiple types: adrenergic receptors:
ß - Liver and Muscle by way of cAMP
alpha- Liver and Muscle by way of Ca++ and IP3 (Phospholipase C)
How does the ANS influence glucose homeostasis when blood glucose is LOW?
Ventromedial nucleus –> SYMPATHETIC signal to Liver, Gut, Pancreas (alpha-cells for glucagon), adipose, heart ==> glycogen BREAKDOWN
How does the ANS influence glucose homeostasis when blood glucose is HIGH?
Lateral Nuclei –> PSNS Vagus Nerve signal to ß-cells for insulin ==> glycogen SYNTHESIS
What is Type 1 Glycogen Storage Disease?
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
What is Type 2 Glycogen Storage Disease?
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
What is Type 3 Glycogen Storage Disease?
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
What is Type 4 Glycogen Storage Disease?
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
What is Type 5 Glycogen Storage Disease?
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
What is Type 6 Glycogen Storage Disease?
Hers Disease: deficiency in liver phosphorylase: cannot breakdown glycogen
Hepatomegaly, Hypoglycemia
What is Type 7 Glycogen Storage Disease?
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
What is Type 9 Glycogen Storage Disease?
Liver Phosphorylase Kinase deficiency–> cannot turn on Phosphorylase –> accumulated glycogen
Hepatomegaly; Hypoglycemia
What is Type O Glycogen Storage Disease?
Glycogen Synthase Deficiency–> cannot make glycogen
Fasting hypoglycemia, post-prandial hyperglycemia (can’t put glucose into glycogen), Quick to fatigue
What Vitamin is essential for proper functioning of Glycogen Phosphorylase? What kind of effects would expect from a deficiency?
Vitamin B6/Pyridoxine
Hypoglycemia, Hepatomegaly, Exercise Intolerance, quick to fatigue
