N-(Phosphonacetyl)-L-aspartate inhibition of the enzyme complex of pyrimidine biosynthesis.
The inhibition of aspartate carbamoyltransferase (ACTase) from rat Novikoff tumor by N-(phosphonacetyl)-L-aspartate (PALA) was studied in a substrate mixture permitting endogenous synthesis of carbamoyl phosphate. Among the components required for carbamoyl phosphate synthetase activity, ATP, Mg(C2H3O2)2 and KCl interfered with inhibition by PALA (with added carbamoyl phosphate). The inhibition was also decreased when the concentration of partially purified enzyme was increased. In the system dependent on carbamoyl phosphate synthetase, the 50% inhibitory concentration of PALA was lower than that in the same mixture plus 0.2 mM carbamoyl phosphate, but higher than in the usual simple assay mixture with 0.2 mM carbamoyl phosphate.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001221:Aspartate Carbamoyltransferase / Q000037:antagonists & inhibitors*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008025:Ligases / Q000037:antagonists & inhibitors*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011743:Pyrimidines / Q000096:biosynthesis*; D051381:Rats
D000964:Antimetabolites, Antineoplastic; D009097:Multienzyme Complexes; D009943:Organophosphorus Compounds; D011743:Pyrimidines; C019820:carbamoyl phosphate synthase-aspartatecarbamoyl transferase complex; D001224:Aspartic Acid; D011189:Potassium Chloride; C013195:sparfosic acid; D000255:Adenosine Triphosphate; D001221:Aspartate Carbamoyltransferase; D008025:Ligases; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); D010746:Phosphonoacetic Acid