Inhibition and reactivation of chicken kynurenine formamidase: In vitro studies with organophosphates, N-alkylcarbamates,and phenylmethanesulfonyl fluoride

In studies on the mechanism of avian teratogenesis induced by organophosphorus and methylcarbamate insecticides, chicken liver kynurenine formamidase (KFase) was used as a convenient model for the more difficultly accessible but teratogenically relevant KFase of the yolk sac membrane. The parameters of in vitro KFase inhibition kinetics do not correlate with the teratogenic potency of various organophosphates and N-alkylcarbamates. The phosphorylated, carbamoylated, and sulfonylated enzymes are relatively resistant to reactivation of enzyme activity either spontaneously or by aldoximes or hydroxylamine. This refractory property may contribute to the prolonged in ovo KFase inhibition necessary for the NAD-deficiency type of teratogenesis.