Fructose-1,6-bisphosphatase deficiency is identified in a neonate with recurrent hypoglycemia and lactic acidosis precipitated by fasting. Which specific gluconeogenic step is blocked, and why does gluconeogenesis from lactate fail while gluconeogenesis from galactose remains unaffected?
- A Failure to convert fructose-1,6-bisphosphate to fructose-6-phosphate; galactose enters above the block via glucose-6-phosphate ✓
- B Failure to convert oxaloacetate to phosphoenolpyruvate; galactose bypasses PEPCK
- C Failure to convert pyruvate to oxaloacetate; galactose bypasses pyruvate carboxylase
- D Failure to convert fructose-6-phosphate to glucose-6-phosphate; galactose does not require phosphoglucose isomerase
Correct answer: A. Failure to convert fructose-1,6-bisphosphate to fructose-6-phosphate; galactose enters above the block via glucose-6-phosphate
Explanation
Fructose-1,6-bisphosphatase catalyses a key irreversible step in gluconeogenesis: fructose-1,6-bisphosphate → fructose-6-phosphate. Lactate, alanine, and pyruvate all feed into the lower pathway and must traverse this step. Galactose is converted to glucose-1-phosphate and then glucose-6-phosphate by galactose-1-phosphate uridyltransferase and phosphoglucomutase — entering gluconeogenesis above the blocked step — so oral galactose can rescue hypoglycemia in this disorder.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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