Acivicin inhibits Crithidia fasciculata growth in a serum-free medium and inactivates carbamoyl-phosphate synthetase II in vivo.
1. Crithidia fasciculata was grown in a serum-free medium. 2. Twenty-six hours after addition of 2, 5, 20, 50, and 150 microM acivicin to logarithmically growing organisms, cell counts were decreased to 46, 23, 14, 9.1, and 8.6% of the control, respectively. 3. Guanosine plus cytidine (0.1 mM each) provided complete protection against growth inhibition by 5 microM acivicin. 4. Cells exposed to 10 microM acivicin showed a time-dependent, irreversible inactivation of L-glutamine-dependent carbamoyl-phosphate synthetase II activity; ammonia-dependent synthetase II activity was increased up to 34% of the control. 5. Glutamine (20 mM) protected the enzyme from inactivation in vivo. 6. These results indicate that acivicin acts as an affinity analog of L-glutamine in vivo as it does in vitro.
D000818:Animals; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000037:antagonists & inhibitors*; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D003421:Crithidia / Q000187:drug effects* / Q000254:growth & development; D003470:Culture Media; D003562:Cytidine / Q000494:pharmacology; D006151:Guanosine / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*
D003470:Culture Media; D007555:Isoxazoles; D010080:Oxazoles; D006151:Guanosine; D003562:Cytidine; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); C006303:acivicin