Biotin is covalently attached to carboxylase enzymes via a specific lysine residue in a reaction catalyzed by holocarboxylase synthetase. Multiple carboxylase deficiency in infants can result from either holocarboxylase synthetase deficiency or biotinidase deficiency. Which carboxylase is the mitochondrial rate-regulating enzyme for gluconeogenesis whose activity would be impaired?

• A Acetyl-CoA carboxylase
• B Pyruvate carboxylase ✓
• C Propionyl-CoA carboxylase
• D Methylcrotonyl-CoA carboxylase

Explanation

Pyruvate carboxylase is the mitochondrial biotin-dependent enzyme that catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate, the critical anaplerotic reaction feeding the TCA cycle and providing the substrate for gluconeogenesis via PEPCK. Multiple carboxylase deficiency (MCD) impairs all four biotin-dependent enzymes: pyruvate carboxylase (causing lactic acidosis and hypoglycemia), propionyl-CoA carboxylase (causing propionic acidemia), 3-methylcrotonyl-CoA carboxylase, and acetyl-CoA carboxylase. MCD is treatable with pharmacological doses of biotin.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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