Glucose-6-phosphatase is absent in the liver and kidney in Type Ia glycogen storage disease (von Gierke's disease). A patient with this condition develops SEVERE hypoglycaemia between meals. The metabolic consequence that explains the inability to maintain blood glucose is:

• A Absent glycogenolysis, as phosphorylase requires G6P for activity
• B Excess glycogen synthesis depletes glucose-6-phosphate, trapping glucose intracellularly
• C Inhibition of GLUT2 by accumulated G6P prevents hepatic glucose uptake
• D Failure to release free glucose from both glycogenolysis AND gluconeogenesis, since both pathways converge at glucose-6-phosphate requiring G6Pase to release free glucose ✓

Explanation

Glucose-6-phosphatase in the ER lumen is the final common step for glucose release from BOTH glycogenolysis (G1P → G6P → glucose) and gluconeogenesis (F1,6-BP → G6P → glucose). Without G6Pase, G6P accumulates in the liver — glycogen continues to be synthesised from this G6P — but no free glucose can be exported to blood. Despite active glycogenolysis and gluconeogenesis, the liver cannot produce free glucose, causing profound fasting hypoglycaemia, lactic acidosis (G6P diverted to glycolysis), hyperuricaemia, and hyperlipidaemia.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.