Short term regulation of ureagenesis.
In order to examine the mechanism of the acute response of ureagenesis to amino acid loads, rats were injected intraperitoneally with various doses of a mixture of 20 amino acids. Blood ammonia rose only slightly with doses of 0.5 to 2.0 g/kg, but increased sharply at doses of 3 to 5 g/kg. Carbamyl phosphate synthetase I (EC 2.7.2.5) activity, assayed in intact mitochondria isolated from livers removed 15 min after injection of amino acids, with N-acetylglutamate at its endogenous levels, rose up to 5-fold with increasing doses up to 2 g/kg; no further activation occurred with larger doses. This maximal activity was the same as the activity measured in disrupted mitochondria. Hepatic levels of glutamate and N-acetylglutamate increased approximately linearly with dose of amino acids. The time course of these changes following a dose of 1.5 g/kg was studied. Glutamate, N-acetylglutamate, and carbamyl phosphate synthetase I activity all peaked 5 to 15 min after injection. All of these results were virtually unaltered by omission of arginine from the injected mixture, indicating that the increase in N-acetylglutamate was not attributable to activation by arginine of N-acetylglutamate synthetase. These results indicate that moderate loads of amino acids activate unreagenesis via a rapid increase in N-acetylglutamate levels, secondary to increased mitochondrial glutamate, and independently of injected arginine. This autoregulatory mechanism becomes saturated at large doses of amino acids, and hyperammonemia then supervenes.
D000123:Acetyltransferases / Q000378:metabolism*; D000596:Amino Acids / Q000097:blood / Q000378:metabolism*; D051046:Amino-Acid N-Acetyltransferase; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000378:metabolism*; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000378:metabolism*; D005260:Female; D005971:Glutamates / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology; D009952:Ornithine / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D051381:Rats; D014508:Urea / Q000096:biosynthesis*
D000596:Amino Acids; D005971:Glutamates; D014508:Urea; D001120:Arginine; D009952:Ornithine; D000123:Acetyltransferases; D051046:Amino-Acid N-Acetyltransferase; D010770:Phosphotransferases; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); C016195:N-acetylglutamic acid