Inhibition of urea synthesis by pent-4-enoic acid: potentiation by ammonia.
Pent-4-enoic acid inhibited ureagenesis approximatively 90% in rat hepatocytes incubated with pyruvate, ammonia and ornithine. Inhibition of ureagenesis was much less with alanine as substrate (approximatively 10%). The addition of ammonia led to a drastic dose-dependent inhibition of ureagenesis by pent-4-enoate. Half-maximum effect of ammonia was observed at 0.2 mM concentration. Concomitant cellular concentrations of N-acetylglutamate were also drastically modified by the addition of ammonia as was the accumulation of citrulline. These data suggest that ammonia may seriously interfere with the metabolism of pent-4-enoic acid and leads to a dramatic potentiation of its toxicity.
D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D002956:Citrulline / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000096:biosynthesis*
D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D005971:Glutamates; D000643:Ammonium Chloride; D002956:Citrulline; D014508:Urea; C009785:4-pentenoic acid; C016195:N-acetylglutamic acid