Relation of yolk sac membrane kynurenine formamidase inhibition to certain teratogenic effects of organophosphorus insecticides and of carbaryl and eserine in chicken embryos

Abstract

One type of teratogenic effect induced in chicken embryos by a variety of organophosphorus (OP) and mcthylcarbamate (MC) insecticides is associated with lowered embryo NAD levels. This appears to result from inhibition of kynurenine formamidase, which impairs conversion of tryptophan to essential pyridine nucleotide cofactors. The yolk sac membrane and the embryonic liver contain two types of kynurenine formamidase, one sensitive and the other relatively insensitive to OP and MC inhibitors. The eserine-sensitive enzyme accounts for ~ 26 percent of the overall activity for hydrolysis of N 1N x- diformyl- l-kynurenine . In studies with twenty-one OP insecticides and two MC compounds injected at day 4 of incubation, the inhibition of the eserine-sensitive kynurenine formamidase at day 9 of incubation correlates well with the lowering of NAD levels at day 12 of incubation and the intensity of teratogenic signs. Teratogens of this type combine high potency for inhibiting the relevant kynurenine formamidase in the yolk sac membrane early in development, and possibly in the liver at later stages, with adequate in tiro stability to maintain the inhibition through critical stages of embryogenesis. Thus, kynurenine formamidase joins acetylcholinesterase in the list of OP- and MC-sensitive enzymes of critical physiological significance.