A 6-year-old with MSUD in metabolic crisis has plasma leucine of 3200 µmol/L. Leucine is the most neurotoxic branched-chain amino acid. Which mechanism best explains leucine-induced cerebral edema in MSUD?
- A Leucine competitively inhibits astrocyte glutamine synthetase
- B Leucine disrupts the blood-brain barrier by degrading tight junction proteins
- C Leucine competitively inhibits transport of large neutral amino acids at the blood-brain barrier, causing cerebral amino acid depletion ✓
- D Leucine directly inhibits neuronal Na+/K+-ATPase
Correct answer: C. Leucine competitively inhibits transport of large neutral amino acids at the blood-brain barrier, causing cerebral amino acid depletion
Explanation
Elevated leucine saturates the L-type amino acid transporter (LAT1) at the blood-brain barrier, competitively inhibiting uptake of tyrosine, tryptophan, and other large neutral amino acids. This depletes neurotransmitter precursors in the brain and contributes to cerebral edema. This mechanism is distinct from the ammonia-driven glutamine accumulation seen in urea cycle disorders.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.