Piperonyl Butoxide Metabolism by Cytochrome P-450: Factors Affecting the Formation and Disappearance of the Metabolite-Cytochrome P-450 Complex

Abstract

1. The metabolism of piperonyl butoxide produces a metabolite-cytochrome P-450 complex with an absorbance maximum at 455 nm. This absorbing species is formed rapidly but destroyed only very slowly. The max. absorbance observed in the presence of excess piperonyl butoxide, NADPH and O₂ is proportional to the protein concn.

2. The metabolite-cytochrome P-450 complex is only observable when the cytochrome is in the reduced state. The ability to observe the spectrum upon the addition of reduced pyridine nucleotide, following the oxidation of the cytochrome P-450, depends upon the time elapsed since the max. formation of the metabolite-reduced cytochrome P-450 absorbing species.

3. The presence of the metabolite-cytochrome P-450 complex inhibits the metabolism of piperonyl butoxide and prevents the hexobarbital stimulation of microsomal NADPH oxidation, but does not affect the endogenous rate of NADPH oxidation.

4. Oxidative and conjugative reactions do not appear to be responsible for the removal of the metabolite-cytochrome P-450 complex.

5. The resistance of the metabolite complex to degradation provides additional evidence for its involvement in piperonyl butoxide insecticide synergism.