Role of N-acetylglutamate and acetyl-CoA in the inhibition of ureagenesis by isovaleric acid in isolated rat hepatocytes.
1 and 10 mmol/l isovalerate strongly inhibited urea synthesis in isolated rat hepatocytes incubated with 10 mmol/l alanine and 3 mmol/l ornithine. Isovalerate also markedly decreased N-acetylglutamate levels, and the decrease correlated with the inhibition of urea synthesis by isovalerate. This compound also lowered cellular levels of acetyl-CoA, a substrate of N-acetylglutamate synthase (EC 2.3.1.1). Isovalerate did not significantly affect the cellular levels of ATP and had no direct effect on N-acetylglutamate synthase activity. These results suggest that the inhibition of urea synthesis by isovalerate is due to decrease in N-acetylglutamate levels.
D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000409:Alanine / Q000378:metabolism; D000818:Animals; D005971:Glutamates / Q000378:metabolism*; D045782:Hemiterpenes; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D009952:Ornithine / Q000378:metabolism; D010421:Pentanoic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000096:biosynthesis*; D014631:Valerates / Q000494:pharmacology*
D005971:Glutamates; D045782:Hemiterpenes; D010421:Pentanoic Acids; D014631:Valerates; C008216:isovaleric acid; D000105:Acetyl Coenzyme A; D014508:Urea; D009952:Ornithine; C016195:N-acetylglutamic acid; D000409:Alanine