Glycogen Flashcards
What are the 4 steps for Glycogen synthesis from glucose-6-phosphate?
G6P -> Glucose-1-phosphate (UDP-glucose pyrophosphorylase) + UTP -> UDP-Glucose (Glycogen Synthase) -> Unbranched Glycogen (Branching enzyme) -> Branched Glycogen
What enzyme causes branhced glycogen to become unbranched?
Debranching enzyme
What enzyme breaks down Unbranched Glycogen into Glucose-1-phosphate?
Glycogen phosphorylase
What enzyme converts Glucose-6-phosphate to glucose?
Glucose-6-Phosphatase
Where is Glucose-6-Phosphatase found?
Liver
What enzyme breaks down unbranched glycogen into glucose and is found in lysosomes?
alpha1,4 glucosidase
What does glycogen phosphorylase do?
- Removes glucose molecules from glycogen polymer
- Creates glucose-1-phosphate from unbranched glycogen
- Stops when glycogen branches decreased to 2-4 linked glucose molecules (limit dextrins)
What vitamin stabilises glycogen phosphorylase?
Vitamin B6
What enzyme phosphorylates glycogen phosphorylase?
Glucagon (and epinephrine)
- Becomes more active
- More glucose
How do glucagon and insulin glycogen and glucose levels?
Through phosphorylating enzymes - glucagon
Through dephosphorylation (insulin)
What are the 2 enzymes which glucagon and epinephrine phosphorylate?
- Glycogen phosphorylase (increasing its activity)
- Glycogen synthase (decreasing its activity)
What is the effect of phosphorylation on glycogen phosphorylase’s activity?
(Glucagon and epinephrine phosphorylate glycogen phosphorylase)
Increases activity, more glycogen -> Glucose
What is the effect of phosphorylation on glycogen synthase’s activity?
(Glucagon and epinephrine phosphorylate glycogen synthase)
Decreases its activity
- less glycogen made from glucose
What enzymes are dephosphorylated by insulin?
- Glycogen phosphorylase (decreased activity - less glucose produced)
- Glycogen synthase (increased activity - more glycogen produced)
Describe the pathway inside the cell how epinephrine and glucagon work to activate glycogen phosphorylase?
Same process with glycogen synthase
- Both bind to surface receptors
- Activate Adenyl Cyclase
- Raises cAMP
- Activate protein kinase A
- Phosphorylates intermediatw known as Glycogen phosphokinase A
- Glycogen phosphokinase A then phosphorylates glycogen phosphorylase which breaks down glycogen
How does insulin work inside the cell to affect glycogen phosphorylase?
Same process with glycogen synthase
- Binds to surface receptor
- Activates tyrosine kinase
- TK phosphorylates an enzyme called protein phosphatase 1
- Protein phosphatase 1 (p) can then remove a phosphate group from GPKinase A, glycogen phosphorylase is then not active so you can then get glycogen breakdown
How can glycogen phosphorylase be activated in the absence of hormones?
In muscles
- Calcium/calmodulin complex activated by muscles can directly activate GPKinase A, can then phosphorylate glycogen phosphorylase
- > Glycogen breakdown
What is AMPs effect on Glucose and glycogen enzymes?
Activates Glycogen phosphorylase
-> Glucose
What is the effect of ATP and Glucose on the glucose and glycogen enzymes?
Decreases the activity of glycogen phosphorylase
-> Glucose
What is the effect of Glucose 6-P on the glucose and glycogen enzymes?
Activates/ increases activity of Glycogen synthase
- Glycogen
What enzyme is defective in Von Gierke’s disease (1a)(Glycogen Storage Disease Type 1a)?
Glucose-6-phosphate deficiency (Type 1a)
What is defective in Von Gierke’s disease (1b)(Glycogen Storage Disease Type 1b)?
Glucose transporter deficiency
When and how does Von Gierke’s disease present?
Infancy (2-6 months of age)
- Severe hypoglycemia between meals (lethargy, seizures, lactic acidosis)
- Enlarged liver (excess glycogen) -> Liver failure
What cycle becomes dysfunctional in those with Von Gierke’s disease?
Cori cycle (lactate cycle)
- G6P cannot be converted to glucose in liver
- Lactate builds up -> acidosis
How is Von Gierke’s disease diagnosed?
- DNA testing (preferred)
- Liver biopsy (historical test)
How is Von Gierke’s disease treated?
- Consumption of cornstarch between meals (glucose polymer)
- Avoidance of sucrose, lactose, fructose, galactose (worsen accumulation of G6P)
What is the deficiency in Pompe’s disease (glycogen storage disease type II)?
Acid alpha-glucosidase deficiency (also lysosomal acid maltase)
- Accumulation of glycogen in lysosomes
How does Pompe’s disease (glycogen storage disease type II) present?
- Accumulation of glycogen in lysosomes
- Classic form presents in infancy -> severe disease -> death in child/infant
- Enlarged muscles
- Cardiomegaly -> Death from HF
- Enlarged tongue
- Hypotonia
- Hepatomegaly (from HF)
- NO hypoglycemia / metabolic problems
What is the deficiency in Cori’s disease (glycogen storage disease type III)?
Debranching enzyme
How does Cori’s disease (glycogen storage disease type III) present?
- Hypoglycemia/hepatomegaly in child/infant (not as severe as Von Gierke)
- No lactic acidosis (Cori’s cycle intact)
- Hypotonia/weakness - Muscle involvement (glycogen accumulation) (no
- Gluconeogenesis intact
- Possible cardiomyopathy w. hypertrophy
What is the deficiency in McArdle’s disease (glycogen storage disease type V)?
Muscle glycogen phosphorylase deficiency
- Myophosphorylase deficiency
- Skeletal muscle has unique isoform of G-phosphorylase
- Glycogen not properly broken down in muscle cells
How does McArdle’s disease (glycogen storage disease type V) present?
Adolescence/ early childhood
- Exercise intolerance, fatigue, cramps
- Poor endurance, muscle swelling, and weakness
- Myoglobinuria and C release (especially with exercise)
- Urine may turn dark/red after exercise
- Second wind in exercise
- Flat venous lactate curve w. normal rise in ammonia levels during exercise
What is the deficient enzyme in Andersen disease (type IV)?
Branching enzyme
- Neuromuscular form can present at any age
How does Andersen disease (glycogen storage disease type IV) present?
- Hepatosplenomegaly and failure to thrive in early infancy
- Infantile cirrhosis
- Musscle weakness
- Hypotonia
- Cardiomyopathy -> early childhood death
