Metabolism of tetraorganolead compounds by rat-liver microsomal mono-oxygenase: II. Enzymic dealkylation of tetraethyl lead

Abstract

1. The biological degradation of tetraethyl lead to the triethyl lead cation by rat-liver microsomes from untreated, phenobarbital-pretreated and methylcholanthrene-pretreated rats has been studied; NADPH and oxygen are essential.

2. The reaction is inhibited by CO and can be reactivated in the presence of O₂ by irradiation with u.v. light with a max. at 450nm.

3. Substrate binding to cytochrome P-450 is of type 1.

4. Apparent K_m values for triethyl lead formation in microsomes were determined. The highest activities (i.e. about 2 nmol triethyl lead per nmol cytochrome P-450 per min) and the lowest apparent K_m values (i.e. 7 × 10^-6 M) are found in microsomes from methylcholanthrene-pretreated rats.

5. In microsomes from control and phenobarbital-pretreated rats K_s values from substrate-binding studies (about 2 × 10^-6M) are one order of magnitude lower than the apparent K_m values (3 × 10^-5 M).