Effects of organic acids on the synthesis of citrulline by intact rat liver mitochondria.
Citrulline synthesis, mostly regulated at the carbamoyl-phosphate synthase I (EC 6.3.4.16) step by the intramitochondrial concentration of ATP and/or N-acetylglutamate is tested with four organic acids: propionate, alpha-ketobutyrate, dipropyl-acetate and 4-pentenoate. In the presence of 10 mM succinate, as the oxidizable substrate, citrullinogenesis was only inhibited by propionate and 4-pentenoate. With 10 mM L-glutamate, a significant inhibition was observed with the four acids. After the addition of ATP and N-acetylglutamate to uncoupled mitochondria, no inhibition could be demonstrated with dipropylacetate and 4-pentenoate. However, a slight inhibition remained with propionate and alpha-ketobutyrate. When mitochondria were incubated with 10 mM L-glutamate, ATP decreased with propionate, dipropylacetate and 4-pentenoate. Under the same conditions, N-acetylglutamate synthesis was strongly inhibited by each organic acid. The decrease of N-acetylglutamate synthesis was related to the constant diminution of intramitochondrial acetyl-coenzyme A (CoA) and to the increase of propionyl-CoA with propionate and alpha-ketobutyrate. Acetyl-CoA and propionyl-CoA are respectively substrate and competitive inhibitor of the N-acetylglutamate synthase (EC 2.3.1.1). Each acid displayed its optimum inhibition at concentrations between 1 and 2 mM. At these acid concentrations, mitochondria had the lowest acetyl-CoA content and the highest propionyl-CoA content.
Rabier
D
D
Briand
P
P
Petit
F
F
Kamoun
P
P
Cathelineau
L
L
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002956:Citrulline / Q000096:biosynthesis*; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005971:Glutamates / Q000096:biosynthesis / Q000378:metabolism; D018698:Glutamic Acid; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D014635:Valproic Acid / Q000494:pharmacology*
D000214:Acyl Coenzyme A; D002087:Butyrates; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D005971:Glutamates; D011422:Propionates; D013386:Succinates; D002956:Citrulline; C009061:propionyl-coenzyme A; D018698:Glutamic Acid; C005087:alpha-ketobutyric acid; D014635:Valproic Acid; D000105:Acetyl Coenzyme A; D000255:Adenosine Triphosphate; D019802:Succinic Acid; C009785:4-pentenoic acid; C029658:propionic acid; C016195:N-acetylglutamic acid