In classic maple syrup urine disease (MSUD), the enzymatic defect involves the branched-chain alpha-keto acid dehydrogenase (BCKAD) complex. This complex requires multiple vitamins as cofactors. High-dose thiamine (vitamin B1) is therapeutically beneficial in some MSUD variants because thiamine pyrophosphate (TPP) is a cofactor for which component of BCKAD?

• A E2 subunit (dihydrolipoamide acyltransferase)
• B E1 subunit (branched-chain alpha-keto acid decarboxylase) ✓
• C E3 subunit (dihydrolipoamide dehydrogenase)
• D Regulatory kinase subunit

Explanation

The branched-chain alpha-keto acid dehydrogenase complex (BCKAD) is structurally analogous to pyruvate dehydrogenase. Its E1 component (decarboxylase) requires thiamine pyrophosphate (TPP) as a tightly-bound cofactor for the initial oxidative decarboxylation step. In thiamine-responsive MSUD, a point mutation reduces the enzyme's affinity for TPP; pharmacological doses of thiamine can overcome this by mass action, partially restoring E1 activity. The E2 subunit uses lipoic acid; the E3 subunit uses FAD and NAD+. Only ~10% of MSUD patients are thiamine-responsive.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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