A 6-month-old infant presents with hepatomegaly, fasting hypoglycemia, and failure to thrive. Liver biopsy shows massive glycogen accumulation. Biochemical analysis reveals absent glucose-6-phosphatase activity. In this condition, which metabolic pathway is specifically blocked that explains the inability to maintain fasting blood glucose?
- A Glycogenolysis, because glycogen phosphorylase cannot release glucose from glycogen
- B Both glycogenolysis and gluconeogenesis, because glucose-6-phosphate cannot be dephosphorylated to free glucose ✓
- C Gluconeogenesis only, because oxaloacetate cannot be converted to phosphoenolpyruvate
- D Glycolysis, because glucose-6-phosphate accumulation inhibits hexokinase
Correct answer: B. Both glycogenolysis and gluconeogenesis, because glucose-6-phosphate cannot be dephosphorylated to free glucose
Explanation
In Von Gierke disease (GSD type Ia), glucose-6-phosphatase deficiency blocks the final step shared by both glycogenolysis and gluconeogenesis — the hydrolysis of glucose-6-phosphate to free glucose. Glycogen can be degraded normally to glucose-6-phosphate, and gluconeogenesis can produce glucose-6-phosphate, but neither pathway can release free glucose into the blood, causing profound fasting hypoglycemia and hepatic glycogen accumulation.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.