Glycogen Storage disease Flashcards
What is a glycogen storage disease
- Class of more than 10 distinct disorders of glycogen metabolism
- Results in either an increase or decrease in amount of glycogen
What are the 2 main tissues glycogen storage diseases affect
- Liver
- Muscle
- The storage sites of glycogen
Name 1 type of GSD
- GSD1
2. Type 1 glycogenosis
Who first discovered GSD1
- Von Grerke in 1929
2. Sometimes referred to as Grerke’s disease
What did Carl and Gerty Cori discover
- 1952
2. Demonstrated that GSD1 was due to deficiency of an enzyme- glucose-6-phosphatase
Describe the Cori cycle
- In the liver lactate is converted to pyruvate which is converted to glucose by gluconeogenesis
- This glucose forms glycogen in the muscle
- Glycogen forms pyruvate which is converted to lactate
- Lactate is transported in the blood to the liver
What is G6Pase
- Enzyme that is involved in the terminal step of glycogen breakdown and gluconeogenesis
- It catalyses the hydrolysis of glucose-6-phosphate to glucose + inorganic phosphate
- Water is added for this breakdown
Where are the 3 tissues that contain G6Pase
- Liver
- Kidney
- Intestint
Describe where G6Pase is in the liver
- Liver has 2 main cells- hepatocytes and bile duct cells (transport bile)
- G6Pase is in the hepatocytes
Where is G6Pase in the kidney
- In the proximal convoluted tubule cells
Describe the structure of the intesting
- Finger like projections which increase SA
- Goblet cells- mucous which lubricates the contents of the intestine
- Stem cells
- Paneth cells- contain lysozyme
- Pit cells- secrete prostaglandin
- Enteroendocrine- secrete hormones
- Enterocyte (absorptive)- G6Pase
Give a summary of the steps of glycogen breakdown
- (Glycogen phosphorylase) Glycogen + phosphate –> Glycogen(n-1) + glucose-1-phosphate
- (phosphoglucomutase) Glucose-1-phosphate glucose-6-phosphate
- (G6Pase) Glucose-6-phosphate + H2O –> Glucose + Pi
Show the steps of gluconeogenesis
- Lactate pyruvate
- Pyruvate –> fructose-6-phosphate
- (Phosphoglucoisomerase) Fructose-6-phosphate Glucose-6-phosphate
- (G6Pase) Glucose-6-phosphate + H2O –> Glucose + Pi
What does a mutase do
- Moves functional groups
Where is G6Pase localised
- In the endoplasmic reticulum
How does Glucose-6-phosphate enter the endoplasmic reticulum
- It is polar so needs help
2. Uses T1- a transporter
What happens once G6P has entered the endoplasmic reticulum
- It can be hydrolysed by G6Pase to glucose and inorganic phosphate
What happens once G6P has been hydrolysed
- The glucose is transported out of the ER by T3
2. The inorganic phosphate is transported out of the ER by T2
What else is needed in the ER
- Stabilising protein in the membrane
2. Needed for intact G6Pase activity
What is G6Pase an example of
- A multi-component enzyme system
How is glucose removed from the cytoplasm out of the cell
- Using a facilitated transporter- GLUT2
What is a problem with this method of glycogen breakdown
- Glycolysis occurs in the cytoplasm
- Glycolysis: G–>G6P
- Gluconeogenesis G6P–>G
- Can’t occur simultaneously as produce a futile cycle
What is the name of Hexokinase IV in the lvier
- Glucokinase
What does glucokinase do
- Catalysis conversion of Glucose –> G6P
Describe what happens when there is high glucose in the hepatocyte
- Glucose is taken up and converted to G6P by GK
2. Goes through glycolysis
Describe what happens when there is low glucose in the hepatocyte
- Want to produce glucose
- Entry of G6P into the ER and converted to G
- GK translocates into the nucleus (so it doesn’t convert G back to G6P)
Why are there different forms of GSD1
- There are defects in different components of G6Pase system
Name the different types of GSD1
- 1a- catalytic subunit defect
- 1b- glucose-6-phosphate trasporter defect (T1)
- 1c- Inorganic phosphate transporter defect (T2)
- 1asp- Stability protein (Sp) defect
How common is GSD
- 1/100000 births
