Suicide inactivation of lactoperoxidase by 3-amino-1,2,4-triazole.
Amitrole (3-amino-1,2,4-triazole) meets the criteria for a suicide (mechanism-based) inhibitor of lactoperoxidase. Amitrole causes rapid inactivation of lactoperoxidase only in the presence of hydrogen peroxide, and the kinetics are consistent with a suicide mechanism. Approximately 7 mol of radiolabeled amitrole binds covalently per equivalent of lactoperoxidase activity lost. The visible spectrum of lactoperoxidase inactivated by amitrole is unchanged, suggesting that covalent modification of the heme prosthetic group does not occur. The 13C NMR spectrum of lactoperoxidase inactivated by [13C]amitrole shows unique resonances which support the hypothesis that covalent binding occurs on the protein moiety. The similarities between lactoperoxidase and thyroid peroxidase suggest a similar mechanism for inhibition of thyroid hormone synthesis by amitrole.
Doerge
D R
DR
Department of Agricultural Biochemistry, University of Hawaii, Honolulu 96822.
Niemczura
W P
WP
D000640:Amitrole / Q000494:pharmacology*; D007700:Kinetics; D007784:Lactoperoxidase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D011506:Proteins / Q000032:analysis
D011506:Proteins; D007784:Lactoperoxidase; D000640:Amitrole