Not only hyperammonaemia and increased plasma glutamine levels but also decreased plasma arginine concentration is found as a common biochemical nominator in urea cycle defects (except arginase 1 deficiency). Arginine is a conditionally endogenous semi-essential amino acid. Its endogenous synthesis is decoupled between intestine and kidneys. In intestine, citrulline is formed by CPS1, whereas ASS and ASL form arginine from circulating plasma citrulline in proximal tubular cells of kidneys.
Low arginine concentrations might also be important for the pathophysiology of urea cycle defects.
You may want to refresh your knowledge of arginine metabolism other than in the urea cycle. It is linked to nitric oxide (NO), creatine, and polyamine metabolism. See ref 12.
There is no evidence that impaired synthesis of polyamines contributes to the neurotoxicity of patients with urea cycle defects, whereas disturbed nitric oxide (NO) and creatine metabolism is considered as an important mechanism.
