A 4-year-old child presents with hypoglycemia, lactic acidosis, and hepatomegaly. Plasma alanine and pyruvate are elevated. Enzyme assay shows deficiency of pyruvate carboxylase. Which metabolic consequence directly explains the lactic acidosis in this condition?

• A Increased flux through pyruvate dehydrogenase complex producing excess acetyl-CoA
• B Pyruvate cannot be converted to oxaloacetate, causing pyruvate accumulation and its reduction to lactate by LDH ✓
• C Excessive gluconeogenesis from alanine depletes NAD+, driving lactate formation
• D Impaired Cori cycle in skeletal muscle leads to peripheral lactate overproduction

Explanation

Pyruvate carboxylase converts pyruvate to oxaloacetate for gluconeogenesis and TCA anaplerosis. Its deficiency causes pyruvate accumulation, which is reduced to lactate by LDH, causing lactic acidosis. PDH converts pyruvate to acetyl-CoA, not OAA. Option C misrepresents the mechanism. The Cori cycle involves liver-muscle lactate exchange but is not primarily impaired here.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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