Glycogen storage diseases Flashcards
what is GSD1?
a deficiency of glucose-6-phosphatase, which catalyses the terminal step in glycogenolysis and gluconeogenesis
G6P + water <=> glucose + Pi
Causes a decrease in glucose levels
tissue specific localisation of G6Pase in liver
made up of parenchymal (the hepatocytes) and non-parenchymal cells
G6Pase is localised in hepatocytes
Non-parenchymal cells are cholangiocytes (biliary epithelial cells), endothelial cells and fat storing cells
tissue specific localisation of G6Pase in kidney
localised in the PCT of nephron
tissue specific localisation of G6Pase in intestine
localised in the absorbative enterocytes
other cells in intestine are the entero-endocrine cells (release GLP1 hormone) and paneth cells (bacteriocidal cells, secreting lysozyme)
roles of GLP1
delays stomach emptying
prepares the intestine for food
increases insulin sensitivity
where is G6Pase localised inside hepatocyte cells?
In ER lumen
G6Pase catalyses hydrolysis of G6P to glucose + Pi
G6P transported into ER lumen by T1
Pi transported out of ER by T2
glucose transported out of ER by T3
what is the futile cycle?
glucose that is transported out of ER is then converted back to G6P by glucokinase (in liver)
G6P then re-enters ER lumen through T1
G6P hydrolysed - whole process repeats in endless cycle
how is futile cycle controlled?
occurs in high glucose conditions
Stops in low glucose conditions, due to the movement of glucokinase into the nucleus
futile cycle in high glucose conditions?
glucose moves into the cell via GLUT2 transporter
glucose also produced by G6Pase in ER lumen (moves into cytosol via T3)
glucokinase is available to convert glucose to G6P
G6P can either re-enter ER lumen to be hydrolysed again, or enter glycolysis
futile cycle in low glucose conditions?
G6P is hydrolysed to glucose inER lumen and enters cytosol via T3
glucokinase localises into nucleus in low glucose conditions
glucose is not converted back to G6P
glucose enters bloodstream via GLUT2 transporter to increase blood glucose levels
The type of GSD1 produced after a mutation depends where the mutation occurs?
Type:
1a - mutation in catalytic subunits
1b - T1
1c - T2 (Pi transporter)
1aSP - in stabilising protein
secretion of cortisol
anterior pituitoary gland secretes ACTH ]ACTH causes the adrenal cortex to release cortisol (glucocorticoid)
cortisol inhibits ACTH secretion via negative feedback
what happens when cortisol reaches a cell
lipid soluble -diffuse through plasma membrane
binds to glucocorticoid receptor - complex translocates into nucleus, and acts as a transcription factor
binds to gluocorticoid response elements (GREs)
turn on/off expression
G6Pase gene has GREs within promoter
3 symptoms of glycogen storage disease
fasting-induced hypoglycaemia (2-4hr post prandially) <4mM
growth failure
protruding abdomen - increase glycogen deposition, causing enlarged liver (hepatomegaly)
symptoms of the autonomic NS of fasting hypoglycaemia? 3
sweating, hunger, tremor
neuroglycopenia (affecting the brain) symptoms of fasting hypoglycaemia? 5
parasthesia (pins/needles)
personality changes
fatigue
seizures
coma/death
