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

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. 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 450 nm. Substrate binding to cytochrome P-450 is of type 1. Apparent Km 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 Km values (i.e. 7 X 10(-6) M) are found in microsomes from methylcholanthrene-pretreated rats. In microsomes from control and phenobarbital-pretreated rats Ks values from substrate-binding studies (about 2 X 10(-6) M) are one order of magnitude lower than the apparent Km values (3 X 10(-5) M).