Maple syrup urine disease (MSUD) is caused by deficiency of the branched-chain alpha-keto acid dehydrogenase complex. Which cofactor is required by this mitochondrial multienzyme complex, and which B-vitamin supplementation may partially rescue function in thiamine-responsive MSUD?

• A Pyridoxal phosphate (B6)
• B Biotin (B7)
• C Cobalamin (B12)
• D Thiamine pyrophosphate (TPP, B1) ✓

Explanation

The branched-chain alpha-keto acid dehydrogenase complex (BCKDH) requires five cofactors: thiamine pyrophosphate (TPP), lipoic acid, FAD, NAD+, and CoA. In thiamine-responsive MSUD (a less severe variant), residual enzyme activity can be augmented by high-dose thiamine supplementation, improving metabolic control alongside dietary restriction of leucine, isoleucine, and valine. Biotin is required by carboxylases (acetyl-CoA carboxylase, pyruvate carboxylase). B12 is needed for methylmalonyl-CoA mutase.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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