A 2-year-old with maple syrup urine disease (MSUD) presents in metabolic crisis. Plasma shows elevated leucine, isoleucine, and valine with their respective keto acids. The enzyme complex deficient in MSUD is structurally homologous to which other mitochondrial enzyme complex?

• A Succinate dehydrogenase
• B Pyruvate dehydrogenase complex ✓
• C HMG-CoA lyase
• D Acyl-CoA dehydrogenase

Explanation

Branched-chain alpha-keto acid dehydrogenase (BCKDH) is structurally and mechanistically homologous to the pyruvate dehydrogenase complex (PDC) and alpha-ketoglutarate dehydrogenase complex — all three use the same five cofactors (TPP, lipoic acid, CoA, FAD, NAD+) and share the same regulatory mechanism (phosphorylation/dephosphorylation of the E1 subunit). BCKDH deficiency leads to accumulation of branched-chain amino acids and their neurotoxic keto acids, particularly alpha-keto-beta-methylvalerate from isoleucine. Leucine's keto acid (alpha-ketoisocaproate) is particularly neurotoxic.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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