N-CARAMYLGLUTAMATE (CARBAGLU): EFFECT ON UREAGENESIS IN N-ACETYLGLUTAMATE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. N-acetylglutamate (NAG) is an essential allosteric cofactor of mitochondrial carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle in ureotelic animals. Without NAG, the enzymatic activity of CPSI is virtually undetectable and thus, the deficiency of NAG would cause a block in ureagenesis, the degree of which would depend on the degree of NAG deficiency. It is believed that the concentrations of NAG within the mitochondria control the activity of CPSI and as such regulate ureagenesis. The purpose of this protocol is to study the effect of N-Carbamylglutamate (Carbaglu) on the incorporation of [15N]ammonia into urea as a measure of restoration of ureagenesis capacity in patients with inherited N-acetylglutamate synthase deficiency diagnosed by DNA testing