Inhibition of urea-cycle activity by high concentrations of alanine.
1. Conditions are described in which high intracellular alanine concentrations inhibit urea-cycle flux in isolated hepatocytes. 2. Inhibition of urea-cycle flux by added alanine is DL-cycloserine-insensitive and is accompanied by an increase in intracellular citrulline and a decrease in ornithine. 3. Argininosuccinate synthetase (EC 6.3.4.5) activity in rat liver cytosol is inhibited by alanine in a competitive manner with respect to citrulline. It is concluded that this effects is the primary cause of inhibition of urea-cycle flux by alanine.
D000409:Alanine / Q000494:pharmacology*; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001124:Argininosuccinate Synthase / Q000037:antagonists & inhibitors; D003600:Cytosol / Q000201:enzymology; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011392:Proline / Q000378:metabolism; D051381:Rats; D014508:Urea / Q000096:biosynthesis / Q000378:metabolism*
D000641:Ammonia; D014508:Urea; D011392:Proline; D001124:Argininosuccinate Synthase; D000409:Alanine