In vitro metabolism of 1,2-dihaloethanes to ethylene.
1,2-Dichloroethane (DCE), a solvent and byproduct of the manufacture of polymers, and 1,2-dibromoethane, a soil fumigant, are known to be metabolized by conjugation with glutathione (GSH) to yield mercapturic acid derivatives. An alternate route of metabolism of the GSH conjugate involves beta-elimination of halide ion to form an olefin. In the present study, ethylene production from DCE was measured by gas chromatography in rat tissues as an index of this latter route of metabolism. The rate of enzymic ethylene production was linear over a 1-hr incubation time and from 1 to 8 mg of protein per ml reaction volume. The temperature optimum for ethylene formation from DCE was 55 degrees C and no distinct pH optimum was observed. DCE metabolism was highly dependent on the presence of reduced GSH. Metabolic activity was limited to hepatic and renal cytosolic fractions. The reaction was inhibited only by p-chloromercuribenzoic acid and by diethyl maleate and methyl iodide, which are substrates for GSH S-transferases. (S-(-2-Chloroethyl)-DL-cysteine . HCl, an analog of the conjugate formed from DCE and GSH, was nonenzymically converted to ethylene.
D000818:Animals; D001711:Biotransformation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015946:Ethylene Dibromide / Q000378:metabolism*; D005025:Ethylene Dichlorides / Q000378:metabolism*; D005030:Ethylenes / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051381:Rats
D004791:Enzyme Inhibitors; D005025:Ethylene Dichlorides; D005030:Ethylenes; D006842:Hydrocarbons, Brominated; D006843:Hydrocarbons, Chlorinated; D015946:Ethylene Dibromide; D005978:Glutathione