Inhibition of L-asparagine synthetase by mucochloric and mucobromic acids.
Mucochloric and mucobromic acids are powerful inhibitors of tumoral and pancreatic L-asparagine synthetases. Two nitrogen donors, L-glutamine and ammonia, can be used by these enzymes; at a concentration of 1 mmol/l, mucochloric and mucobromic acids preferentially inhibit the utilization of ammonia as opposed to L-glutamine in vitro. Using the tumoral enzyme, kinetic analysis revealed that mucochloric acid produced inhibition which was apparently noncompetitive with ammonia but competitive with L-glutamine. In molar excess, L-glutamine and dithiothreitol effectively antagonized such inhibition; dialysis, however, failed to reverse established inhibition. These findings, suggest that the drugs operate by covalent attachment to crucial sulfhydryl functions on the enzyme.
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001217:Aspartate-Ammonia Ligase / Q000037:antagonists & inhibitors*; D002460:Cell Line; D005663:Furans / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology; D007700:Kinetics; D008025:Ligases / Q000037:antagonists & inhibitors*; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D009374:Neoplasms, Experimental / Q000201:enzymology; D010179:Pancreas / Q000201:enzymology; D013329:Structure-Activity Relationship
D005663:Furans; D000643:Ammonium Chloride; D005973:Glutamine; C014117:mucochloric acid; C014116:mucobromic acid; D008025:Ligases; D001217:Aspartate-Ammonia Ligase; D008274:Magnesium