Maple syrup urine disease (MSUD) is caused by deficiency of branched-chain alpha-keto acid dehydrogenase (BCKAD) complex. Which cofactors are required for BCKAD function?

• A PLP (pyridoxal phosphate), NAD+ and CoA
• B TPP, lipoic acid, CoA, FAD and NAD+ ✓
• C Biotin, ATP, HCO3- and acetyl-CoA
• D FMN, FAD, iron-sulfur clusters and CoQ

Explanation

BCKAD is structurally and mechanistically analogous to pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex. It is a multienzyme complex requiring five cofactors: thiamine pyrophosphate (TPP, cofactor for E1 component), lipoic acid (covalently bound to E2 dihydrolipoamide acyltransferase), CoA (substrate for E2), FAD (cofactor for E3 dihydrolipoamide dehydrogenase) and NAD+ (substrate for E3). These alpha-keto acid dehydrogenase complexes all share the same cofactor requirements. Biotin is required for carboxylase reactions (pyruvate carboxylase, ACC). PLP is required for aminotransferase reactions. FMN/FAD/iron-sulfur complexes characterise the electron transport chain components.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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