METABOLISM OF HALOFORMS TO CARBON-MONOXIDE .3. STUDIES ON THE MECHANISM OF THE REACTION

Haloforms are metabolized to carbon monoxide by hepatic microsomal mixed function oxidases and this reaction is markedly stimulated by sulfhydryl compounds. Maximal stimulation occurred at 0.5 mM glutathione (GSH). Formation of 1 mole of carbon monoxide (CO) resulted in the disappearance of 2 moles of GSH and the production of 1 mole of oxidized glutathione (GSSG). Incubation of 13CHBr3, or 12CHBr3 in the presence of 18O2, resulted in the formation of similarly enriched 13CO or C18O respectively. Furthermore, a primary isotope effect was observed when CDBr3 served as the substrate. Dibromocarbonyl is an intermediate in the reaction since 2-oxothiazolidine-4-carboxylic acid (OTZ) was detected when CHBr3 was incubated in the presence of cysteine. In addition, when 13CHBr3 was used, a similarly enriched [13C]OTZ was formed. Based on these observations, the following mechanism for the conversion of haloforms to CO is proposed: CHX → COHX3 → X2CO; X2CO + GSH → GS(C = O)X; GS(C = O)X + GSH → GSSG + :C = O. © 1979.