Rat liver microsomal metabolism of propyl halides.
The in vitro metabolism of 1-propyl halides (chloride, bromide, and iodide) by hepatic microsomes from phenobarbital-induced rats was examined. The following metabolites were detected: propene, 1,2-epoxypropane, 1,2-propanediol, propionic acid, and undefined species bound to protein (for propyl chloride). The addition of exogenous glutathione to the incubation mixture led to the production of S-(1'-propyl)glutathione and S-(2'-hydroxy-1'-propyl)glutathione. The ratio of the metabolites resulting from C1-C2 functionalization [propene, 1,2-propanediol, and S-(2'-hydroxy-1'-propyl)glutathione] to that resulting from C1 functionalization (propionic acid) increased as the halide progressed down the halide order chloride bromide, and iodide. Mechanisms which rationalize the distribution of propyl halide metabolites as a function of the halide are discussed. The preferred mechanism interprets that the results obtained are a consequence of the partitioning of the initial metabolic transformation between alpha-hydroxylation and halogen oxygenation pathways.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006846:Hydrocarbons, Halogenated / Q000378:metabolism*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D006846:Hydrocarbons, Halogenated; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D005978:Glutathione