Fructose-1,6-bisphosphatase (FBPase-1) deficiency is a disorder of gluconeogenesis. During prolonged fasting or high-fructose intake in an affected infant, which metabolite accumulates and causes lactic acidosis?
- A Fructose-6-phosphate — inhibits glycolysis upstream
- B Dihydroxyacetone phosphate — inhibits triose phosphate isomerase
- C Fructose-1,6-bisphosphate — allosterically activates pyruvate kinase and inhibits pyruvate dehydrogenase, forcing pyruvate to lactate ✓
- D Glucose-6-phosphate — inhibits hexokinase causing hypoglycaemia
Explanation
Without FBPase-1, gluconeogenesis is blocked: fructose-1,6-bisphosphate accumulates, which allosterically activates pyruvate kinase (increasing glycolytic flux toward pyruvate) and inhibits the pyruvate dehydrogenase complex (impairing pyruvate oxidation to acetyl-CoA). Excess pyruvate is reduced to lactate by LDH, causing lactic acidosis. During fasting, inability to generate glucose from gluconeogenic precursors causes hypoglycaemia; during high fructose intake, fructose-1-phosphate and subsequently fructose-1,6-bisphosphate accumulate. Treatment: avoid fasting and fructose/sorbitol/glycerol intake.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.