RT Journal Article
SR Electronic
T1 Rat liver microsomal metabolism of propyl halides.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 745
OP 751
VO 22
IS 3
A1 H Tachizawa
A1 T L MacDonald
A1 R A Neal
YR 1982
UL http://molpharm.aspetjournals.org/content/22/3/745.abstract
AB 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.