Biotin (vitamin B7) is a covalently bound cofactor for carboxylase enzymes. Which enzyme's biotin dependence explains the organic aciduria in biotinidase deficiency?

• A Pyruvate carboxylase — deficiency causes lactic acidosis but not organic aciduria
• B Acetyl-CoA carboxylase — deficiency causes impaired fatty acid synthesis only
• C Propionyl-CoA carboxylase — deficiency causes propionyl-CoA accumulation → propionic acidaemia ✓
• D Methylmalonyl-CoA mutase — uses adenosylcobalamin, not biotin

Explanation

Biotinidase cleaves biotin from biocytin (biotinyl-lysine) after protein turnover, recycling biotin. Its deficiency leads to multiple carboxylase deficiency since all four biotin-dependent carboxylases (pyruvate carboxylase, propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, and acetyl-CoA carboxylase) become non-functional. Propionyl-CoA carboxylase deficiency specifically causes propionyl-CoA accumulation → propionic acid and methylcitrate in urine (propionic acidaemia pattern). 3-methylcrotonyl-CoA carboxylase deficiency causes 3-methylcrotonylglycine and 3-hydroxyisovalerate excretion. Biotin supplementation is curative if started early.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.