Question 186

Question:

An inherited metabolic disorder of carbohydrate metabolism is characterized by an abnormally increased concentration of hepatic glycogen with normal structure and no detectable increase in serum glucose concentration after oral administration of fructose. These two observations suggest that the disease is a result of the absence of which of the following enzymes?

Correct Answer: C.  Glucose-6-phosphatase

The deficient enzyme must be common to both pathways of converting glycogen to glucose and of converting fructose to glucose to yield the observed disease. Only Glucose-6-phosphatase (choice C) is common to both pathways. Glucose-6-phosphatase is required in the conversion of Glucose-6-phosphate to glucose, which is the common last step in the pathway of converting both glycogen and fructose to glucose. Deficiency of glucose-6-phosphatase is also known as Von Gierke’s disease or Type I glycogen storage disease.
Fructokinase (choice A) converts fructose to fructose-1-phosphate—the first step in the metabolism of fructose. Deficiency in this enzyme should not effect the conversion of glycogen to glucose. Fructokinase deficiency can lead to a benign disorder called essential fructosuria.
Glucokinase (choice B) is a liver-specific enzyme that converts glucose to glucose-6-phosphate as the first step of glucose metabolism. Deficiency in this enzyme should not effect conversion of glycogen to glucose or conversion of fructose to glucose.
Phosphoglucomutase (choice D) is an enzyme that allows inter-conversion between glucose-1-phosphate and glucose-6-phosphate. Deficiency in this enzyme will impair conversion of glycogen to glucose, but will not impair conversion of fructose to glucose.
UDPG-glycogen transglucosylase (choice E) is an enzyme that facilitates the incorporation of glucose into glycogen. Deficiency of this enzyme will impair glycogen synthesis.