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Literature summary for 2.3.1.1 extracted from

  • Nissim, I.; Horyn, O.; Nissim, I.; Daikhin, Y.; Caldovic, L.; Barcelona, B.; Cervera, J.; Tuchman, M.; Yudkoff, M.
    Down-regulation of hepatic urea synthesis by oxypurines: xanthine and uric acid inhibit N-acetylglutamate synthase (2011), J. Biol. Chem., 286, 22055-22068.
    View publication on PubMedView publication on EuropePMC

Inhibitors

Inhibitors Comment Organism Structure
isobutylmethylxanthine and other oxypurines containing a 2,6-dione group interfere with the binding of glutamate to the active site of N-acetylglutamate synthetase, thereby decreasing synthesis of N-acetylglutamate, resulting in reduction of citrulline and urea synthesis. Isobutylmethylxanthine significantly increases the apparent Km for glutamate and decreases velocity of N-acetylglutamate synthetase, with little effect on carbamoylphosphate synthase-1. Inhibition is reversed by supplementation with N-carbamylglutamate Rattus norvegicus
uric acid significantly increases the apparent Km for glutamate and decreases velocity of N-acetylglutamate synthetase, with little effect on carbamoylphosphate synthase-1. Inhibition is reversed by supplementation with N-carbamylglutamate Rattus norvegicus
xanthine significantly increases the apparent Km for glutamate and decreases velocity of N-acetylglutamate synthetase, with little effect on carbamoylphosphate synthase-1. Inhibition is reversed by supplementation with N-carbamylglutamate Rattus norvegicus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.6
-
acetyl-CoA pH 7.4, 37°C Rattus norvegicus
6
-
L-glutamate pH 7.4, 37°C Rattus norvegicus

Organism

Organism UniProt Comment Textmining
Rattus norvegicus
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
liver
-
Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
acetyl-CoA + L-glutamate
-
Rattus norvegicus CoA + N-acetyl-L-glutamate
-
?

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.17
-
pH 7.4, 37°C Rattus norvegicus xanthine
0.24
-
pH 7.4, 37°C Rattus norvegicus uric acid
0.36
-
pH 7.4, 37°C Rattus norvegicus isobutylmethylxanthine