Inhibition of urea synthesis by pent-4-enoate associated with decrease in N-acetyl-L-glutamate concentration in isolated rat hepatocytes.
Pent-4-enoate at 0.1 to 1.0 mM strongly inhibited urea synthesis in isolated rat hepatocytes. Pent-4-enoate at the same concentrations markedly decreased concentrations of N-acetyl-L-glutamate, an essential activator of carbamoyl-phosphate synthase-I (EC 2.7.2.5), and the decrease was well in parallel with the inhibition of urea synthesis by pent-4-enoate. This compound also lowered cellular concentrations of acetyl-CoA, a substrate of acetylglutamate synthase (EC 2.3.1.1). Pent-4-enoate in a dose of 1 mM did not significantly affect cellular concentrations of ATP, and had no direct effect on acetylglutamate synthase activity. These results suggest that the inhibition of urea synthesis by pent-4-enoate is due to decrease in N-acetyl-L-glutamate concentration and that the decrease is probably brought about by decreased rate of its synthesis due to the lowered concentration of cellular acetyl-CoA.
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002956:Citrulline / Q000096:biosynthesis; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005947:Glucose / Q000096:biosynthesis; D005971:Glutamates / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D014508:Urea / Q000096:biosynthesis*; D014631:Valerates / Q000494:pharmacology
D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D005971:Glutamates; D014631:Valerates; D002956:Citrulline; D000105:Acetyl Coenzyme A; D000255:Adenosine Triphosphate; D014508:Urea; C009785:4-pentenoic acid; D005947:Glucose