Nags-flox Mouse

NAGS, or N-acetylglutamate synthase, is a mitochondrial enzyme (E.C. 2.3.1.1) [2]. It catalyzes the formation of N-acetylglutamate (NAG), an essential allosteric activator of carbamylphosphate synthetase I (CPSI) in the urea cycle [2]. In microorganisms and plants, it also functions in the arginine biosynthetic pathway [3].

In tumor cells, median expression of NAGS mRNA was higher in glioblastoma multiforme (GBM), glioma, and stomach adenocarcinoma (STAD) samples compared to the matched normal tissue, while in lung adenocarcinoma (LUAD), its expression did not differ from normal tissue. High NAGS expression was associated with an unfavorable outcome in patients with glioblastoma and GBM, and low NAGS expression was associated with an unfavorable outcome in patients with LUAD [1]. Inherited NAGS deficiency results in hyperammonemia, presumably due to the loss of CPSI activity [2].

In conclusion, NAGS is crucial for the urea cycle by activating CPSI through the production of NAG. Its abnormal expression is associated with certain tumors and its deficiency leads to hyperammonemia. Studies on NAGS contribute to understanding the mechanisms of tumorigenesis and urea cycle-related disorders.