Metabolism of methyltertiary-butyl ether by rat hepatic microsomes
- 1 March 1990
- journal article
- research article
- Published by Springer Science and Business Media LLC in Archives of Toxicology
- Vol. 64 (2), 157-160
- https://doi.org/10.1007/bf01974403
Abstract
Exposure to methyltertiary-butyl ether (MTBE), a commonly used octane booster in gasoline, has previously been shown to alter various muscle, kidney, and liver metabolic activities. In the present study, the metabolism of MTBE by liver microsomes from acetoneor phenobarbital-treated Sprague-Dawley rats was studied at concentrations of up to 5 mM MTBE. Equimolar amounts oftertiary-butanol, as measured by head-space gas chromatography, and formaldehyde were formed. TheVmax for the demethylation increased by 4-fold and 5.5-fold after acetone and phenobarbital treatments, respectively. The apparentKm value of 0.70 mM using control microsomes was decreased slightly after acetone treatment, but was increased by 2-fold after phenobarbital treatment. The metabolism of MTBE (1 mM) was inhibited by 35% by monoclonal antibodies against P450IIE1, the acetone/ethanol inducible form of cytochrome P450, suggesting a partial contribution by this isozyme. A single 18-h pretreatment of rats with 1 or 5 ml/kg MTBE (i. p.) resulted in a 50-fold induction of liver microsomal pentoxyresorufin dealkylase activity but no change inN-nitrosodimethylamine demethylase activity. These trends in activity agreed with immunoblot analysis which showed an elevation in P450IIB1 but no change in P450IIE1 levels.Keywords
This publication has 19 references indexed in Scilit:
- Mechanism of induction of cytochrome P-450ac (P-450j) in chemically induced and spontaneously diabetic ratsArchives of Biochemistry and Biophysics, 1988
- Ethanol-, fasting-, and aceton-inducible cytochromes P-450 in rat liver: regulation and characteristics of enzymes belonging to the IIB and IIE gene subfamiliesBiochemistry, 1988
- Ligand-dependent maintenance of ethanol-inducible cytochrome P-450 in primary rat hepatocyte cell culturesBiochemical and Biophysical Research Communications, 1988
- Solvent Toxicology: Recent Advances in the Toxicology of Benzene, The Glycol Ethers, and Carbon TetrachlorideAnnual Review of Pharmacology and Toxicology, 1987
- The P450 Gene Superfamily: Recommended NomenclatureDNA, 1987
- Characterization of ethanol-inducible human liver N-nitrosodimethylamine demethylaseBiochemistry, 1986
- Monoclonal antibodies to ethanol induced cytochrome P-450 that inhibit aniline and nitrosamine metabolismBiochemical Pharmacology, 1986
- Carbon tetrachloride‐induced lipid peroxidation dependent on an ethanol‐inducible form of rabbit liver microsomal cytochrome P‐450FEBS Letters, 1985
- Oxidative demethylation of t-butyl alcohol by rat liver microsomesBiochemical and Biophysical Research Communications, 1980
- Repression of dimethylnitrosamine-demethylase by typical inducers of microsomal mixed-function oxidasesBiochemical Pharmacology, 1975