Ljubica Caldovic, Julie J Ahn, Jacklyn Andricovic, Veronica M Balick, Mallory Brayer, Pamela A Chansky, Tyson Dawson, Alex C Edwards, Sara E Felsen, Karim Ismat, Sveta V Jagannathan, Brendan T Mann, Jacob A Medina, Toshio Morizono, Michio Morizono, Shatha Salameh, Neerja Vashist, Emily C Williams, Zhe Zhou, Hiroki Morizono
Ammonia, which is toxic to the brain, is converted into non-toxic urea, through a pathway of six enzymatically catalyzed steps known as the urea cycle. In this pathway, N-acetylglutamate synthase (NAGS, EC 2.3.1.1) catalyzes the formation of N-acetylglutamate (NAG) from glutamate and acetyl coenzyme A. NAGS deficiency (NAGSD) is the rarest of the urea cycle disorders, yet is unique in that ureagenesis can be restored with the drug N-carbamylglutamate (NCG). We investigated whether the rarity of NAGSD could be due to low sequence variation in the NAGS genomic region, high NAGS tolerance for amino acid replacements, and alternative sources of NAG and NCG in the body...
October 17, 2023: Journal of Inherited Metabolic Disease