The NAGS gene provides instructions for making the enzyme N-acetylglutamate synthase. This enzyme is needed for the urea cycle, a series of reactions that occurs in liver cells. The urea cycle processes excess nitrogen, generated when protein is used by the body, into a compound called urea that is excreted by the kidneys. Excreting the excess nitrogen prevents it from accumulating in the form of ammonia, which is toxic, especially to the nervous system.
N-acetylglutamate synthase controls the production of a compound called N-acetylglutamate in the mitochondria, the energy-producing centers in cells. N-acetylglutamate is necessary to activate the enzyme carbamoyl phosphate synthetase I. This enzyme controls the first step of the urea cycle, in which excess nitrogen compounds are incorporated into the cycle to be processed.
Approximately 12 NAGS gene mutations have been identified in people with N-acetylglutamate synthase deficiency. A mutated NAGS gene may result in an N-acetylglutamate synthase enzyme that is shorter than normal or the wrong shape, or may prevent the enzyme from being produced at all.
The shape of an enzyme affects its ability to control a chemical reaction. If the N-acetylglutamate synthase enzyme is damaged or missing, N-acetylglutamate will be produced in lower-than-normal amounts, or not at all. This shortage of N-acetylglutamate interferes with proper activation of carbamoyl phosphate synthetase I, preventing it from fulfilling its role in the urea cycle. Excess nitrogen is not converted to urea for excretion, and ammonia accumulates in the body. This accumulation causes neurological problems and other signs and symptoms of N-acetylglutamate synthase deficiency.