N-acetylglutamate synthetase (NAGS) deficiency: diagnosis, clinical observations and treatment.

Abstract

NAGS plays an important role in the short term regulation of urea synthesis. This enzyme has extensively been studied by Shigesada and Tatibana in rodents 1 ,2,3. We have purified human NAGS in order to find out what substrate concentrations should be used in an assay for human liver. The kinetic results including product inhibition studies are compatible with a rapid equilibrium random bibi mechanism. In the absence of arginine the Km are for Acetyl CoA 4.4 mmol/1, for glutamate 8.2 mmol/1. The Ki of N-acetylglutamate is at 0.5 mmol/1. Arginine approximately triples the activity (half maximum activation at about 30 µmol/1), and appears to lower the Km of acetyl CoA, but not of glutamate4.