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Literature summary 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

EC Number Inhibitors Comment Organism Structure
2.3.1.1 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
2.3.1.1 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
2.3.1.1 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]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.3.1.1 0.6
-
 acetyl-CoA pH 7.4, 37°C Rattus norvegicus
2.3.1.1 6
-
 L-glutamate pH 7.4, 37°C Rattus norvegicus

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.1 Rattus norvegicus
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.1.1 liver
-
 Rattus norvegicus
-

Substrates and Products (Substrate)

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

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.3.1.1 0.17
-
 pH 7.4, 37°C Rattus norvegicus xanthine
2.3.1.1 0.24
-
 pH 7.4, 37°C Rattus norvegicus uric acid
2.3.1.1 0.36
-
 pH 7.4, 37°C Rattus norvegicus isobutylmethylxanthine