Biotin (vitamin B7) serves as a covalently-attached cofactor for carboxylase enzymes. The enzyme that covalently attaches biotin to the apocarboxylase (biotinylation) and the clinical consequence of its deficiency are:

• A Biotinidase; deficiency causes secondary biotin deficiency and multiple carboxylase deficiency
• B Biotin carboxyl carrier protein; deficiency causes isolated acetyl-CoA carboxylase deficiency
• C Holocarboxylase synthetase; deficiency causes neonatal multiple carboxylase deficiency ✓
• D Avidin; deficiency from overripe egg whites causes acquired biotin deficiency

Explanation

Holocarboxylase synthetase (HCS) attaches biotin covalently to the epsilon-amino group of a specific lysine residue in each apocarboxylase (pyruvate carboxylase, propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, acetyl-CoA carboxylase). HCS deficiency causes neonatal-onset multiple carboxylase deficiency with severe metabolic acidosis, skin rash, alopecia, and immune dysfunction. Biotinidase cleaves biotin from degraded carboxylases for recycling; its deficiency causes late-onset (3 months) multiple carboxylase deficiency with additional neurological features (seizures, optic atrophy). Both respond to pharmacological biotin supplementation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.