A neonate with citrullinaemia type I (argininosuccinate synthetase deficiency) presents with hyperammonaemia. The treatment involves: (1) sodium benzoate + sodium phenylacetate and (2) arginine supplementation. The mechanism of arginine supplementation in this condition is:
- A Arginine provides an alternate pathway for ammonium elimination via the carbamoyl phosphate synthetase I reaction
- B Arginine becomes an essential amino acid in citrullinaemia; supplementation drives the partial urea cycle producing citrulline, which is excreted, removing 2 nitrogen atoms per molecule ✓
- C Arginine activates N-acetylglutamate synthase, stimulating residual CPS-I activity
- D Arginine chelates ammonium ions, facilitating renal excretion
Explanation
In citrullinaemia type I, the cycle is blocked at argininosuccinate synthetase. Arginine supplementation provides arginine for arginase → ornithine → carbamoyl phosphate → citrulline. Each citrulline molecule exported carries one nitrogen (from carbamoyl phosphate = ammonia via CPS-I) without re-entering the blocked step, allowing net nitrogen removal. Additionally, arginine is not synthesised from ornithine (which accumulates) via the blocked pathway, making it conditionally essential. Sodium benzoate/phenylacetate conjugate glycine/glutamine to provide alternative N excretion routes.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.