Acute and chronic effects of carbamyl glutamate on blood urea and ammonia

Abstract

Carbamyl glutamate injected into normal rats produced no change in blood urea levels. Rats fed a high-protein diet or starved for 48 h had increased blood urea. Carbamyl glutamate injection induced a further increase in the levels of urea in their blood. Also, carbamyl glutamate administered in the drinking water of normal mice produced an increase in blood urea, which was accompanied by a decrease in blood ammonia. The application of these findings to the treatment of urea cycle enzymopathies is discussed.

Carbamyl glutamate prevents the potentiation of ammonia toxicity by sodium benzoate

“…1), as suggested by Maswoswe et al [6,9] and confirmed by the enhancing effect of carnitine on NAGA synthesis and urea production in mice injected with sodium benzoate and ammonium acetate [14]. On the other hand, carbamyl glutamate is an in vitro activator of CPS [15] and of urea synthesis [13] and has been shown to reduce hyperammonaemia in humans [1,8]. It was likely, then, that the protective effect of carbamyl glutamate in mice treated with ammonium acetate plus sodium benzoate could depend on the restoration of the capacity of urea synthesis, decreased by benzoate.…”

“…The administration of carbamyl glutamate has been reported to be of benefit in some cases of hyperammonaemia [1,8] and increases urea synthesis in exprimental animals [13].…”

Therapeutic use of carbamylglutamate in the case of carbamoyl‐phosphate synthetase deficiency

“…Treatment with CG has been discussed, but so far has only been used in Nacetylglutamate synthetase deficiency (O'Conner et al 1985). This is the first proof that CG stimulates the remaining carbamoyl-phosphate synthetase and increases the rate of urea synthesis.…”

“…Treatment with CG in a kinetic variant or a partial deficit of CPS has been discussed (Guffon et al 1995;O'Conner et al 1985), but has never been clinically proven until now.…”

Mutation analysis in patients with N-acetylglutamate synthase deficiency

“…Definite diagnosis was based on enzyme studies using liver biopsy samples . NAGSD is treatable by oral application of carbamylglutamate O'Connor et al, 1985O'Connor et al, , 1989Guffon et al, 1995;Morris et al, 1998;Plecko et al, 1998]. …”