Flashcards in Glycogen Deck (44):
0
Glycogen-epinephrine
Tissue
Liver and muscle
1
Glycogen-glucagon
Tissue?
Liver
2
Glucogen-insulin
Tissue?
Liver and muscle
3
Protein responsible for glycogen synthesis
Glycogen synthase
4
Protein responsible for glycogen hydrolysis
Glycogen phosphorylase
6
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)
7
Epinephrin - glycogen pathway
1. 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)
2. Epinephrin α receptor (LIVER) --> increased calcium from endoplasmic reticulum. Calcium can activate glycogen phosphorylase kinase :
1. Directly
2. Via calcium-calmodulin in muscle during contraction
8
Alternative epinephrin glycogen pathway
Epinephrin α receptor (LIVER) --> increased calcium from endoplasmic reticulum. Calcium can activate glycogen phosphorylase kinase :
1. Directly
2. Via calcium-calmodulin in muscle vis contraction
9
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)
9
Insulin action on glycogen synthesis inhibits glycogen phosphorylase via
Tyrosine kinase dimer receptor (liver + muscle)
- inhibits glycogen phosphorylase via protein phosphatase
- induce glycogen synthase
10
Glucagon and epinephrin inhibit glycogen synthesis via
Protein kinase A is a glycogen synthase inhibitor
11
Glycogen bonds
a-(1,6) bonds
a-(1,4) bonds
12
Glycogen in skeletal muscles
It undergoes glycogenolysis to glucose-1-P -->glucose 6-P which is rabidly metabolized during exercise
13
Glycogen bonds
branches: a-(1,6) bonds
linkages: a-(1,4) bonds
14
Glycogen in hepatocytes function
1. Storage
2. Glycogenolysis to maintain blood sugar at appropriate levels
15
Glycogen phosphorylase
Cleaves glucose-1-P residues off branched glycogen until four remain before a branch point
16
Glycogen enzymes
1. UDP-glucose pyrophosphorylase
2. Glycogen synthase
3. Branching enzyme
4. Glycogen phosphorylase
5. 4-a-D-glucanotransferase (debranching enzymes)
6. a-1,6-glucosidase (debranching enzymes)
7. α-1,4-glucosidase
17
Glycogen building block
UDP-glucose
18
UDP-glucose pyphosphorylase function
Glucose -1-P to UDP-glucose (to be ready for glycogen formation)
20
glycogen - Branching enzymes - function and types
Makes linear glycogen
- 4-a-D-glucanotransferase
- a-1,6-glucosidase
20
a-1-6-glucosidase function
Cleaves off the last glucose 1-P on the branch
21
4-a-D-glucanotransferase function
Moves 3 glucose-Ps from the brunch to the linkage (leaves 1)
22
Acid maltase
A small amount of glycogen is degraded in in lysosomes by a-1,4-glycosidase
23
Limit dextrin
One to four residues remaining on a branch after glycogen phosphorylase has already shortened it
24
Glycogen storage diseases
How many tyoes
12 types all resulting in abnormal glycogen metabolism and accumulation of glycogen within cells
26
Glycogen storage disease type 1 / mode of inheritance
Von Gierke disease AR
27
Glycogen storage disease type 2 / mode of inheritance
Pompe disease AR
28
Glycogen storage disease type 3 / mode of inheritance
Cori disease AR
28
Mode of inheritance of glycogen storage diseases type 1-4
AR
29
Glycogen storage disease type 4 / mode of inheritance
McArble disease AR
31
Von Gierke disease (type 1) pathophysiology
Glucose-6-phosphatase deficiency --> impaired gluconeogenesis and glycogenolysis
32
Von Gierke disease (type 1) findings
1. Severe fasting hypoglycemia
2. Increased glycogen in liver
3. Increased blood lactate
4. Hepatomegaly
5. incdreased TG
6. increased Uric acid (Gout)
33
Von Gierke disease (type 1) treatment
Frequent oral glucose/cornstarch
Avoidance of fructose and galactose
34
Pompe disease (type 2) pathophysiology
lysosomal a-1,4-glucosidase with α-1,4-glycosidase activity (Acid maltase) deficiency
34
Pompe disease (type 2) findings
1. Cardiomyopathy
2. hypertrophic cardiomyopathy
3. exercise intolerance
4. Systemic findings leading to early death
35
Pompe disease (type 2) findings
1. Cardiomegaly
2. hypertrophic cardiomyopathy
3. exercise intolerance
4. Systemic findings leading to early death
37
Cori disease (type 3) pathophysiology
a-1,6-glucosidase deficiency
37
McArdle disease (type 4) pathophysiology
Skeletal muscle phosphorylase (myophosphorylase deficiency)
38
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
40
McArdle disease (type 4) findings / mechanism
1. Increased glycogen in muscle, but cannot break it down leading to painful muscle cramps
2. Myoglobinuria (red urine) with strenuous exercise
3. Arrythmia from electrolyte abnormalities
4. 2nd wind phenomenon noted during exercise due to increased muscular blood flow
41
There any problem with gluconeogenesis in Cori disease?
No. It is intact
42
It is useful for Glycogen storage disease diagnosis
Periodic acid-Schiff stain
43
Skeletal muscle phosphorylase
Myophosphorylase
44