Glycogen Storage disease 2

Question 1

What gene does the defect that causes GSD occur in and what does it effect

Answer 1

1. Chromosome 17

2. Effects response elements on promoter

Question 2

Give an example of a response element that is affected

Answer 2

1. Glucocorticoid

Question 3

What is glucocorticoid and give an example

Answer 3

1. It is a hormone

2. e.g. cortisol

Question 4

What happens to cortisol if blood glucose drops

Answer 4

1. It may be secreted
2. Can pass through the plasma membrane as made from cholesterol
3. Once in the cytoplasm it binds to a receptor- glucocorticoid receptor
4. Once it binds to the receptor the complex translocates into the nucleus
5. Once inside the nucleus, the complex can bind to glucocorticoid response elements and can enhance or inhibit gene expression
6. e.g. G6Pase gene- cortisol increases the expression

Question 5

What are the symptoms of GSD1

Answer 5

1. Protruding abdomen
2. Fasting- induced hypoglycaemia
3. Growth retardation

Question 6

What causes a protruding abdomen

Answer 6

1. Enlarged liver- hepatomegaly

2. Caused by increased glucogen deposition

Question 7

What causes induced hypoglycaemia when fastign

Answer 7

1. Reduced G6Pase so can’t convert G6P –> Glucose

2. Can’t finish of glycogen breakdown or gluconeogenesis

Question 8

What causes growth retardation

Answer 8

1. Lack of energy

Question 9

What are the typical glucose concentrations in mM1 for normal people and GSD

Answer 9

1. Normal = around 5-5.5

2. GSD= <4

Question 10

What are the symptoms of hypoglycaemia

Answer 10

1. Autonomic- hunger, tremor, sweating

2. Neuroglycopenia- fatigue, paresthesia, personality changes, seizure, coma, impaired brain function

Question 11

What are 4 biochemical characteristics caused by GSD1

Answer 11

1. Hypoglycaemia
2. Hyperlacticacidemia
3. Hyperlipidemia
4. Hyperuricemia

Question 12

What causes hyperlacticacidemia

Answer 12

1. Increase in lactate
2. In glycogen breakdown in the muscle lactate is produced and leaves the muscle going to liver
3. In the liver lactate is converted to pyruvate and then back to glucose
4. BUT in GSD1, G6P can’t be converted to G so [G6P] increases
5. G6P is converted to lactate in glycolysis which increases [lactate]
6. Why there is increased deposition of glycogen in the liver–>hepatomegaly

Question 13

What is the normal and GSD1 concentrations of triglycerides and cholesterol in mg/dl

Answer 13

1. Triglycerides: normal-<150, GSD1-600

2. Cholesterol: normal-<200, GSD1- 400-600

Question 14

When does hyperlipidemia tend to occur and what happens

Answer 14

1. Puberty

2. Develop xanthoma- deposition of lipid over extensor surfaces e.g elbows

Question 15

What are the 2 causes of hyperlipidemia

Answer 15

1. Increased glycerol

2. Increased fatty acids

Question 16

Why is there an increase in glycerol in GSD1

Answer 16

1. In liver there is an increase in G6P which is in equilibrium with F6P which can be converted to Fructose-1,6-diphosphate
2. Fructose-1,6-diphosphate is broken down to GAP (glyceraldehyde-3-phosphate) and DHAP (dihydroxyacetone phosphate) in equilibrium with each other
3. Only GAP continues along glycolysis
4. In GSD1, DHAP is converted to glycerol-3-phosphate
5. Glycerol-3-phosphate is converted to glycerol

Question 17

Why is there an increase in fatty acid synthesis in GSD1

Answer 17

1. Increased G6P which increases fatty acid biosynthesis as it increases pyruvate concentration
2. Pyruvate can enter the TCA cycle- in mitochondria where it is converted to acetyl-CoA
3. Acetyl-CoA is converted to citrate by citrate synthase
4. Citrate doesn’t enter TCA it instead exits mitochondria into cytoplasm and is converted back to Acetyl-CoA by ATP citrate lyase
5. More acetyl-CoA in the cytoplasm
6. Acetyl-CoA is converted to malonyl CoA by acetyl CoA carboxylase (catalyses first step in fatty acid + cholesterol biosynthesis)

Question 18

What is hyperuricemia

Answer 18

1. Elevated levels of uric acid

Question 19

Why is there elevated levels of uric acid in GSD1

Answer 19

1. Predominantly thought o be because of increased lactate which is excreted in the kidneys in preference to uric acid
2. Uric acid is also a breakdown product of purine catabolism
3. Increase in G6P, increases pentose phosphate pathway converting it to purines, so increased catabolism so increased uric acid

Question 20

What is the main symptom of hyperuricemia

Answer 20

1. Gout- causes intense pain
2. Due to deposition of uric acid in the synovia of joints
3. e.g. great toe, foot, ankle