Maple syrup urine disease (MSUD) is caused by deficiency of branched-chain alpha-keto acid dehydrogenase complex (BCKAD). This enzyme requires which cofactor, also shared by pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase?

• A Pyridoxal phosphate (PLP) only
• B Biotin as the carboxyl carrier
• C Tetrahydrofolate and vitamin B12
• D Thiamine pyrophosphate (TPP), lipoamide, CoA, FAD, and NAD+ (all five cofactors of the dehydrogenase complex) ✓

Explanation

BCKAD, like the other alpha-keto acid dehydrogenase complexes (PDH, alpha-KGDH), requires all five cofactors: thiamine pyrophosphate (TPP) for E1 decarboxylase, lipoamide for E2 acyltransferase, CoA as the acyl group acceptor, FAD for E3 dihydrolipoamide dehydrogenase, and NAD+ as the final electron acceptor. Deficiency of E3 (dihydrolipoamide dehydrogenase) therefore impairs all three complexes simultaneously, which is the basis of combined PDH/KGDH/BCKAD deficiency (lipoamide dehydrogenase deficiency, MSUD variant).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.