Carbamoyl Phosphate Synthase 1, abbreviated as CPS1, is activated by its natural activator N-Acetyl glutamate, which in turn is synthesized from acetyl-CoA and glutamic acid in the reaction catalyzed by N-Acetyl glutamate synthase, commonly called NAGS. N-Acetyl Glutamate is required for the Urea cycle to take place.
Deficiency in N-Acetyl Glutamate Synthase or a genetic mutation in the gene coding for the enzyme, will lead to urea cycle failure in which ammonia is not converted to urea, but rather accumulated in blood leading to the condition called Type I Hyperammonemia. This is a severe neonatal disorder with fatal consequences, if not detected immediately upon birth.
The chromosome found to be carrying the gene encoding for N-Acetyl Glutamate synthetase is chromosome 17q (q stands for longer arm of the chromosome) in humans and chromosome 11 in mice. In both organisms, the chromosome consists of seven exons and six introns and non-coding sequence.
The cause for this disorder is a single base deletion that led to frameshift mutation, and thus the error in gene's coding for this specific enzyme.
Presentation and treatment
The symptoms are visible within the first week of life and if not detected and diagnosed correctly immediately consequences are fatal.
Although there is currently no cure, treatment includes injections of structurally similar compound, N-Carbamoyl phosphate, an analogue of N-Acetyl Glutamate. Scientists that discovered this compound theorized that injected N-Carbamoyl Phosphate could trick the organism into substituting N-Carbamoyl Phosphate for N-Acetyl Glutamate and thus activate much required CPS1 enzyme, the catalyst in the very first reaction of the Urea Cycle. This treatment mitigates the intensity of the disorder.
If symptoms are detected early enough and the patient is injected with this compound, levels of severe mental retardation can be slightly lessened, but brain damage is irreversible.