Lecture 25 - GSD2 Flashcards
(17 cards)
What is Fasting Hypoglycaemia
Blockage at last step of glycogenolysis and gluconeogenesis
G-6-P is not converted to Glucose and Pi
Inability to produce glucose in times of deprivation leads to fall in blood glucose
What are some autonomic symptoms of hypoglycaemia
Sweating
hunger
tremor
What are some symptoms of neuroglycopenia from hypoglycaemia
Impaired brain funtion
coma
seizures
fatigue
personality change
pins and needles
What is Hyperlacticacidemia
in GSDI the excess glucose-6-phosphate cannot be converted to glucose.
Instead it enters the glycolytic pathway and is
converted to lactate
What is Hyperlipidaemia
Triglyceride, fatty acids and cholesterol levels are way above normal
At puberty, GSDI patients develop Xanthomas (over extensor surfaces)
What are xanthomas
Yellow bumps or plaques that develop under the skin
What are normal and GSDI triglyceride levels
normal - <150 mb/dL
GSDI - 600
What are normal and GSDI cholesterol levels
Normal - <200
GSDI - 400-600
What is the mechanism for glycerol synthesis in hyperlipidaemia
G6P -> F6P by phosphoglucolsamarase
F6P+ATP -> F1,6DP + ADP by phosphofructokinase (PFK)
F1,6DP -> Glyceraldehyde-3-phosphate by aldolase - NORMAL
OR to dihydroxyacetone phosphate
DAP <-> Glycerol-3-phosphate by Glycerol-3-phosphate dehydrogenase
Glycerol-3-phosphate + ADP <-> Glycerol + ATP by glycerol kinase
Glycerol is the backbone of triglycerides
What is the mechanism for increased fatty acid synthesis in Hyperlipidaemia
Increased Glucose-6-phosphate -> Pyruvate (glycolysis)
Pyruvate enters mt - converted to acetyl CoA (catalysed by pyruvate dehydrogenase PDH)
Pyruvate + COASH + NAD+ -> Acetyl CoA + CO2 + NADH
Acetyl CoA can’t leave mt - converted to citrate by citrate synthase
A CoA + OAA -> Citrate + CoASH
Citrate leaves mt, converted back to A CoA and OAA in cyto by ATP citrate lyase
Citrate + CoA + ATP -> OAA + A CoA + ADP + Pi
A CoA –> malonyl CoA (first step in FA biosynthesis) by A CoA Carboxylase
What does Malonyl CoA also do besides the first step for FA Synthesis
inhibits FA entry into the mt for Beta oxidation
What is Hyperuricemia
Increased uric acid
What are the 2 possible mechanism for hyperuricemia
Increased purine synthesis
Reduced uric acid clearance by the kidney
What is the mechanism for increased purine synthesis in hyperuricemia
Increased G6P -> Ribose-5-phosphate
Increased purine synthesis (A and G)
A+G are converted to Xanthine
Xanthine converted to uric acid
Why might uric acid removal be reduced in the kidney, leading to hyperuricemia
Uric acid and lactate are excreted
through the same renal transporter. There is thus a competition between lactate and uric acid for excretion
What is a symptom of hyperuricemia
Gout - deposition of uric acid crystals in the synovia of joints - especially the big toe, foot ankle - causing intense acute pain
What are some treatments of GSDI
Dietary - to avoid hypoglycaemia - frequent meals and nocturnal enteral feeding through nasogastric tube
Orthotopic Liver transplantation
Kidney transplant if renal failure occurs
