A neonate presents on day 3 of life with profound hypoglycemia, lactic acidosis, and hepatomegaly. Liver biopsy shows increased glycogen with normal structure. Enzyme assay reveals absent glucose-6-phosphatase activity. Which metabolic process is primarily blocked, causing both fasting hypoglycemia AND post-glucagon failure to raise blood glucose?
- A Glycogenolysis only — glycogen cannot be broken down
- B The terminal step of both glycogenolysis and gluconeogenesis, as both converge at glucose-6-phosphate release ✓
- C Glycolysis — pyruvate cannot enter the TCA cycle
- D The glycogen synthase reaction — UDPG cannot be incorporated
Correct answer: B. The terminal step of both glycogenolysis and gluconeogenesis, as both converge at glucose-6-phosphate release
Explanation
Glucose-6-phosphatase (deficient in GSD Type Ia, von Gierke disease) cleaves glucose-6-phosphate to free glucose. This is the final common step for BOTH glycogenolysis (glycogen → G1P → G6P) and gluconeogenesis (pyruvate/lactate/amino acids → G6P). Blocking this step means neither pathway can export glucose, explaining why glucagon (which stimulates glycogenolysis) fails to raise blood glucose. The resulting G6P accumulation drives glycolysis → lactate, causing lactic acidosis.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.