Metabolism of halogenated methanes and macromolecular binding.
Dihalomethanes are metabolized to carbon monoxide both in vivo and in vitro. The reaction is catalyzed by a hepatic microsomal cytochrome P-450 dependent mixed function oxidase system. Bioorganic mechanism studies suggest an initial oxygen insertion reaction followed by rearrangement to a formyl halide intermediate which in turn decomposes to yield carbon monoxide. In vitro studies show that 14C-dichloromethane becomes covalently bound to both microsomal protein and lipid. The similar characteristics of metabolism to carbon monoxide and covalent binding suggests that a common intermediate, perhaps the formyl halide, may be involved. Dihalomethanes are also metabolized to formaldehyde, formic acid, and inorganic halide. A glutathione transferase, located in hepatic cytosol fractions, appears to be involved. Reaction mechanism studies suggest that a S-hydroxymethyl glutathione intermediate may yield formaldehyde or be diverted via formaldehyde dehydrogenase/S-formyl glutathione hydrolase to yield formic acid. Haloforms are also metabolized in vitro to carbon monoxide by a hepatic microsomal cytochrome P-450 dependent mixed function oxidase system. This reaction is a markedly stimulated by sulfhydryl compounds.
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005557:Formaldehyde / Q000378:metabolism; D006846:Hydrocarbons, Halogenated / Q000378:metabolism*; D066298:In Vitro Techniques; D008697:Methane / Q000031:analogs & derivatives / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D051381:Rats; D014018:Tissue Distribution
D006846:Hydrocarbons, Halogenated; D005557:Formaldehyde; D012313:RNA; D002248:Carbon Monoxide; D004247:DNA; D008697:Methane