An infant presents with severe developmental delay, hypotonia, recurrent hypoglycemia, and marked lactic acidosis. Plasma alanine is elevated, and administration of a vitamin cofactor partially improves the acidosis. Pyruvate cannot be converted to oxaloacetate in cultured fibroblasts. Which cofactor is deficient in function at the defective enzyme?

• A Biotin ✓
• B Thiamine pyrophosphate
• C Pyridoxal phosphate
• D Tetrahydrobiopterin

Explanation

Pyruvate carboxylase, the first enzyme of gluconeogenesis, converts pyruvate to oxaloacetate in mitochondria and requires biotin as a covalently bound prosthetic group carrying CO2. Its deficiency causes lactic acidosis, hypoglycemia, and hyperalaninemia because pyruvate accumulates and is transaminated to alanine. Thiamine pyrophosphate serves pyruvate dehydrogenase and transketolase, not pyruvate carboxylase, which is the key distinction between the two major pyruvate-fate disorders.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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