Lecture 24 - Glycogen Storage Diseases 1 Flashcards
What are the tissues with the most glycogen storage
Liver and Muscle
What is GSD1 also known as
Type 1 Glycogenosis
or Von Gierke disease
What is G6Pase
G6Pase is an enzyme involved in the terminal step of both glycogen breakdown
(glycogenolysis) and gluconeogenesis (the formation of glucose from non-glucose
precursors e.g. pyruvate or lactate)
What are the 3 tissues G6Pase is located in
Liver G6Pase - hepatocytes
Small Intestine - present in enterocyctes (absorptive cells) on vili
Kidney - Proximal convoluted tubule cells of nephron
What does the liver do
Gluconeogenesis mostly from lactate and the new glucose is sent back to the muscle
Why is glucose 6 phosphatase important
catalyses terminal steps of glycogenolysis and gluconeogenesis
(slide 7)
What is glycogen turned into after it is catalysed by glycogen phosphorylase
Glycogen n-1 + glucose-1-phosphate
Revise Cori cycle
What is the conversion of glucose to glucose 6-phosphate catalysed by
Hectokinase
Glucokinase (liver only)
What are the 2 broad types of liver cells
Parenchymal - hepatocytes
Non-parenchymal - Cholangiocytes (bile duct epithelial)
Endothelial
Fat storing (ITo) - vitamin A
What is the use of mucus in the intestines
Prevent acid from stomach breaking down villi
peristalsis
What do paneth cells contain
Bacteriacidal lysozyme
What do enter-endocrine cells contain
GLP-1 receptors
What does GLP-1 do
Signals to the stomach to delay emptying
Prepare intestine for onslaught of food
Improves insulin sensitivity
Improves beta cell sensitivity
Where is the G6Pase localised in the cell of eg. a hepatocyte
Endoplasmic Reticulum
facing inside of the lumen
What are the two parts to the ER
Lumen and cytoplasmic contacting part
Is glucose 6-phosphate lipid or water soluble
Water - ER is mostly lipids
What do T1 do
Transport G6P into the ER
What T2 and T3 do
Transport Glucose (T3) and inorganic phosphate (T2) out of the ER
What do stabilising proteins do
Maintain integrity of catalysing subunit
What would happen if glucokinase was present in the cytoplasm of a hepatocyte with glucose present
Glucose converted to G6P before ER converts it back to glucose (futile cycle)
How do you get around the futile cycle during high glucose times
GLUT2 in membrane
glucose will enter and be converted to G6P by glucokinase enters glycolysis
What happens in times of low glucose levels
GK moves away into the nucleus, no G6P is made, futile cycle is created, glucose leaves cell and increases blood glucose levels
What is G6Pase an example of
Multi-component enzyme system
What is the defect for each component of the system
Ia - Catalytic subunit
Ib Glucose-6-phosphate Transporter (T1)
Ic Inorganic Phosphate Transporter (T2)
IaSP Stabilising protein (calcium-dependent)
What is the rate of GSD type 1
1/100,000 births
Where is the G6Pase gene located
Chromosome 17 (17q21)
What is an example of a glucocorticoid
Cortisol
What is cortisol secretion controlled by
Anterior pituitary gland
(ATCH)
What are the 3 different steroids (secreted from adrenal cortex)
Mineralocorticoids
Glucocorticoids
???
What is secreted from the adrenal glands medulla
????
What is the Glucocorticoid mechanism of action
Binding of cortisol to the glucocorticoid receptor induces translocation of the hormone/receptor complex into the nucleus.
Here the complex acts as a transcription factor regulating the expression of target genes through the glucocorticoid
response element (GRE) in the promoter region of genes
What are some symptoms of GSDI
- Protruding abdomen – this is due to hepatomegaly (enlarged liver – as a result of
increased deposition of glycogen) - Fasting-induced hypoglycaemia (occurs 2-4hr post-prandially)
Normal glucose concentration is approximately 5.0-5.5mM (100mg/dl)
GSDI glucose concentration is less than 4.0mM (<70mg/dl) - Growth failure
What are some biochemical characteristics of GSD1
- Hypoglycaemia
- Hyperlacticacidemia
- Hyperlipidaemia
- Hyperuricemia
