Metabolism & Bioenergetics MCAT Practice Question
A 3-year-old boy presents with hepatomegaly, failure to thrive, and recurrent hypoglycemic seizures despite frequent feeding. Laboratory studies show severe fasting hyperlactemia (8.2 mmol/L; normal <2), normal to low blood glucose (55 mg/dL), and elevated alanine levels. Genetic testing reveals biallelic mutations in GDE1 (glycogen debranching enzyme). A liver biopsy demonstrates extensive glycogen accumulation with abnormally short outer branches. Which of the following best explains why this patient develops hyperlactemia despite low blood glucose?
Answer choices
- AGlycogen debranching enzyme deficiency directly impairs hexokinase function, trapping glucose-6-phosphate and shunting it toward anaerobic glycolysis
- BAccumulated glycogen physically compresses hepatic vasculature, reducing oxygen delivery and forcing anaerobic metabolism
- CInability to complete glycogenolysis limits glucose availability, driving increased reliance on anaerobic glycolysis and gluconeogenesis from amino acids, both of which generate lactate as an end productCorrect answer
- DDebranching enzyme deficiency causes direct inhibition of pyruvate dehydrogenase, preventing lactate oxidation and causing lactate accumulation
- EExcessive branching of glycogen limits glucose-6-phosphatase access to glucose-1-phosphate, preventing hepatic glucose output and triggering compensatory lipolysis with lactate generation
- FGlycogen accumulation depletes hepatic NAD+ pools, impairing lactate dehydrogenase function and preventing lactate clearance by the liver
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