Potentiation by ammonia of the metabolic effects of pent-4-enoate in isolated rat hepatocytes.
The metabolic effects of pent-4-enoate were studied in isolated rat hepatocytes; 1 mM-pent-4-enoate did not significantly inhibit gluconeogenesis from lactate, alanine and glycerol, but significantly decreased glucose synthesis from pyruvate. The addition of 1 mM-NH4Cl led to a drastic inhibition of glucose synthesis from all these substrates. In hepatocytes incubated with 10 mM-alanine and 1 mM-oleate, pent-4-enoate at 0.05-1 mM slightly inhibited glucose synthesis and ketogenesis. The addition of ammonia resulted in a dramatic potentiation of the metabolic effects of pent-4-enoate. Half-maximum effect of ammonia was observed at 0.2 mM concentration. Concomitant cellular concentrations of ATP and acetyl-CoA were also decreased by the addition of ammonia, as were lactate/pyruvate ratio and beta-hydroxybutyrate/acetoacetate ratio. These data suggest that ammonia seriously interferes with the cellular metabolism of pent-4-enoate and leads to a dramatic potentiation of its effects.
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000096:biosynthesis; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011766:Pyruvate Carboxylase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D007657:Ketone Bodies; D000105:Acetyl Coenzyme A; D000641:Ammonia; C009785:4-pentenoic acid; D011766:Pyruvate Carboxylase