Glycogen Flashcards
Glycogen-glucagon
Tissue?
Liver
Glycogen-epinephrine
Tissue
Liver and muscle
Glucogen-insulin
Tissue?
Liver and muscle
Protein responsible for glycogen synthesis
Glycogen synthase
Protein responsible for glycogen hydrolysis
Glycogen phosphorylase
Glucagon-glycogen pathway
Glucagon receptor (LIVER) --> adenylate cyclase --> increased cAMP --> PROTEIN KINASE A --> glycogen phosphorylase kinase --> glycogen phosphorylase --> glycogen to glucose (Protein kinase A is a glycogen synthase inhibitor)
Epinephrin - glycogen pathway
- Epinephrin β receptor (liver or muscle) –> adenylate cyclase –> increased cAMP –> PROTEIN KINASE A –> glycogen phosphorylase kinase –> glycogen phosphorylase –> glycogen to glucose (Protein kinase A is a glycogen synthase inhibitor)
- Epinephrin α receptor (LIVER) –> increased calcium from endoplasmic reticulum. Calcium can activate glycogen phosphorylase kinase :
- Directly
- Via calcium-calmodulin in muscle during contraction
Alternative epinephrin glycogen pathway
Epinephrin α receptor (LIVER) –> increased calcium from endoplasmic reticulum. Calcium can activate glycogen phosphorylase kinase :
- Directly
- Via calcium-calmodulin in muscle vis contraction
Insulin action on glycogen synthesis
Tyrosine kinase dimer receptor (liver + muscle)
- inhibits glycogen phosphorylase via protein phosphatase
- induce glycogen synthase (directly or via protein phosphatase)
Insulin action on glycogen synthesis inhibits glycogen phosphorylase via
Tyrosine kinase dimer receptor (liver + muscle)
- inhibits glycogen phosphorylase via protein phosphatase
- induce glycogen synthase
Glucagon and epinephrin inhibit glycogen synthesis via
Protein kinase A is a glycogen synthase inhibitor
Glycogen bonds
a-(1,6) bonds
a-(1,4) bonds
Glycogen in skeletal muscles
It undergoes glycogenolysis to glucose-1-P –>glucose 6-P which is rabidly metabolized during exercise
Glycogen bonds
branches: a-(1,6) bonds
linkages: a-(1,4) bonds
Glycogen in hepatocytes function
- Storage
2. Glycogenolysis to maintain blood sugar at appropriate levels
Glycogen phosphorylase
Cleaves glucose-1-P residues off branched glycogen until four remain before a branch point
Glycogen enzymes
- UDP-glucose pyrophosphorylase
- Glycogen synthase
- Branching enzyme
- Glycogen phosphorylase
- 4-a-D-glucanotransferase (debranching enzymes)
- a-1,6-glucosidase (debranching enzymes)
- α-1,4-glucosidase
Glycogen building block
UDP-glucose
UDP-glucose pyphosphorylase function
Glucose -1-P to UDP-glucose (to be ready for glycogen formation)
glycogen - Branching enzymes - function and types
Makes linear glycogen
- 4-a-D-glucanotransferase
- a-1,6-glucosidase
a-1-6-glucosidase function
Cleaves off the last glucose 1-P on the branch
4-a-D-glucanotransferase function
Moves 3 glucose-Ps from the brunch to the linkage (leaves 1)
Acid maltase
A small amount of glycogen is degraded in in lysosomes by a-1,4-glycosidase
Limit dextrin
One to four residues remaining on a branch after glycogen phosphorylase has already shortened it
Glycogen storage diseases
How many tyoes
12 types all resulting in abnormal glycogen metabolism and accumulation of glycogen within cells
Glycogen storage disease type 1 / mode of inheritance
Von Gierke disease AR
Glycogen storage disease type 2 / mode of inheritance
Pompe disease AR
Glycogen storage disease type 3 / mode of inheritance
Cori disease AR
Mode of inheritance of glycogen storage diseases type 1-4
AR
Glycogen storage disease type 4 / mode of inheritance
McArble disease AR
Von Gierke disease (type 1) pathophysiology
Glucose-6-phosphatase deficiency –> impaired gluconeogenesis and glycogenolysis
Von Gierke disease (type 1) findings
- Severe fasting hypoglycemia
- Increased glycogen in liver
- Increased blood lactate
- Hepatomegaly
- incdreased TG
- increased Uric acid (Gout)
Von Gierke disease (type 1) treatment
Frequent oral glucose/cornstarch
Avoidance of fructose and galactose
Pompe disease (type 2) pathophysiology
lysosomal a-1,4-glucosidase with α-1,4-glycosidase activity (Acid maltase) deficiency
Pompe disease (type 2) findings
- Cardiomyopathy
- hypertrophic cardiomyopathy
- exercise intolerance
- Systemic findings leading to early death
Pompe disease (type 2) findings
- Cardiomegaly
- hypertrophic cardiomyopathy
- exercise intolerance
- Systemic findings leading to early death
Cori disease (type 3) pathophysiology
a-1,6-glucosidase deficiency
McArdle disease (type 4) pathophysiology
Skeletal muscle phosphorylase (myophosphorylase deficiency)
Cori disease (type 3) findings
- Milder form of type 1 with normal blood lactate (and gluconeogenesis is intact)
- Accumulation of limit dextrin-like structures in cytosol
McArdle disease (type 4) findings / mechanism
- Increased glycogen in muscle, but cannot break it down leading to painful muscle cramps
- Myoglobinuria (red urine) with strenuous exercise
- Arrythmia from electrolyte abnormalities
- 2nd wind phenomenon noted during exercise due to increased muscular blood flow
There any problem with gluconeogenesis in Cori disease?
No. It is intact
It is useful for Glycogen storage disease diagnosis
Periodic acid-Schiff stain
Skeletal muscle phosphorylase
Myophosphorylase
blood glucose in McArdle disease
unaffected
