Biotin is covalently attached to carboxylase enzymes via an amide bond with a specific lysine residue, a process catalyzed by holocarboxylase synthetase. Biotinidase then recycles biotin from degraded carboxylases. A child with biotinidase deficiency has defects in which FOUR carboxylases?

• A Pyruvate carboxylase, propionyl-CoA carboxylase, methylmalonyl-CoA mutase, acetyl-CoA carboxylase
• B Pyruvate carboxylase, alpha-ketoglutarate dehydrogenase, propionyl-CoA carboxylase, acetyl-CoA carboxylase
• C Pyruvate carboxylase, propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, transcarboxylase
• D Pyruvate carboxylase, propionyl-CoA carboxylase, acetyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase ✓

Explanation

All four biotin-dependent carboxylases in humans use biotin as the CO2 carrier: (1) pyruvate carboxylase (converts pyruvate to oxaloacetate for gluconeogenesis/TCA anaplerosis), (2) propionyl-CoA carboxylase (converts propionyl-CoA to methylmalonyl-CoA in branched-chain AA/odd-chain fatty acid catabolism), (3) acetyl-CoA carboxylase (converts acetyl-CoA to malonyl-CoA, first committed step of fatty acid synthesis), and (4) 3-methylcrotonyl-CoA carboxylase (leucine catabolism). In biotinidase deficiency, biotin cannot be recycled from degraded carboxylases, causing secondary multiple carboxylase deficiency with organic acidemia, alopecia, dermatitis, and lactic acidosis. Methylmalonyl-CoA mutase uses adenosylcobalamin (vitamin B12), not biotin.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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