Biochemistry 5: Von Gierke

Question 1

What is the reason for using leucine, lysine for pyruvate dehydrogenase deficiency?

Answer 1

Both are ketogenic (NOT glucogenic) amino acids. In other words, neither will form glucose when broken down. Since pyruvate dehydrogenase is the final step in glycolysis (going from the 3-carbon pyruvate, eliminating a CO2, to form the 2-carbon acetyl-CoA, remember??), a defect in PD will be a glycolysis defect.

Question 2

Von Gierke – what are the cholesterol levels?

Answer 2

Elevated. Glucose-6-phosphate ↑ → glycolysis ↑ → acetyl-CoA ↑ (via pyruvate dehydrogenase) → cholesterol ↑

Question 3

Von Gierke – what are the uric acid levels?

Answer 3

High. Glucose-6-phosphate ↑ → HMP shunt ↑ → ribose-5-phosphate ↑ → purine synthesis ↑ → purine breakdown ↑ → uric acid ↑

Question 4

Von Gierke – what are the triglyceride levels?

Answer 4

Elevated. Glucose-6-phosphate ↑ → glycolysis ↑ → acetyl-CoA ↑ → fatty acids ↑ → triglycerides ↑

Question 5

Von Gierke – what are the triglyceride levels?

Answer 5

Elevated. Glucose-6-phosphate ↑ → glycolysis ↑ → acetyl-CoA ↑ → fatty acids ↑ → triglycerides ↑

Question 6

Von Gierke – what are the lactic acid levels?

Answer 6

High. Glucose-6-phosphate ↑ → glycolysis ↑ → pyruvate ↑ / NADH ↑ → lactate ↑

Question 7

Von Gierke – after how many hours of fasting would someone present? Why?

Answer 7

~4 hours (assuming no strenuous exercise). Dietary glucose lasts ~4 hours (if you’re a parent, you’ll note that it’s only about 3-4 hours in-between feedings!!)

Question 8

VLCAD deficiency – after how many hours of fasting would someone present? Why?

Answer 8

Fast of 12 to 16 hours (often occurs following infection/something else that will increase energy demand). Glycogen stores last 24-28 hours; in viral illness, appetite ↓, energy requirements ↑