Self-catalyzed destruction of insect cytochrome [formula omitted

Abstract

Incubation of housefly microsomes with 1-aminobenzotriazole (ABT) resulted in a considerable loss of cytochrome P-450 as measured by its dithionite-reduced CO-difference spectrum. This cytochrome P-450 loss was strictly dependent on NADPH, and was dependent also on both incubation time and ABT concentration. An abnormal porphyrin was isolated from housefly microsomes incubated with ABT and NADPH. Its electronic absorption spectrum was identical to that of an authentic NN- aryl- bridged protoporphyrin IX, a result which suggests that cytochrome P-450 loss was due to self-catalyzed covalent modification of the prosthetic haem group. A cytochrome P-450 monooxygenase activity, aldrin epoxidation, was inactivated by ABT in vitro according to pseudo-first order kinetics typical of suicide substrates. ABT had no detectable toxicity in vivo, but synergized the toxicity of a carbamate insecticide to houseflies. 2-Iso propyl-4- pentenamide , ethynylcyclohexanol, and substituted phenyl propynyl ethers (the latter are known insecticide synergists) cause similar in vitro loss of cytochrome P-450. The amounts of cytochrome P-450 destroyed by these compounds depend on the strain of houseflies (insecticide-resistant or susceptible) and on whether the insects are pretreated with phenobarbital. Cytochrome P-450 induced by phenobarbital in resistant flies appeared to be the most sensitive to these suicide substrates. This suggests that self-catalyzed destruction of cytochrome P-450 is isozyme-selective in the house fly.