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).
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003640:Dealkylation; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology*; D009942:Organometallic Compounds / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013756:Tetraethyl Lead / Q000378:metabolism*
D009942:Organometallic Compounds; D013756:Tetraethyl Lead; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D010634:Phenobarbital