A 3-day-old neonate presents with severe hypoglycemia, hepatomegaly, and lactic acidosis. Fructose-1,6-bisphosphatase assay in liver tissue shows markedly reduced activity. Glucagon infusion fails to raise blood glucose. Which metabolic pathway is primarily blocked?
- A Glycogenolysis
- B Glycolysis
- C Gluconeogenesis ✓
- D HMP shunt
Correct answer: C. Gluconeogenesis
Explanation
Fructose-1,6-bisphosphatase is a key regulatory enzyme of gluconeogenesis, catalysing the irreversible dephosphorylation of fructose-1,6-bisphosphate to fructose-6-phosphate. Its deficiency specifically blocks gluconeogenesis from lactate, amino acids, and glycerol; glycogenolysis remains intact. Glucagon fails to raise glucose because it can only release glucose from glycogen (via glycogenolysis), which becomes exhausted. Lactate accumulates because it cannot be converted to glucose. This is distinct from Von Gierke's disease where G6Pase is deficient.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.