METABOLISM OF HALOFORMS TO CARBON-MONOXIDE .1. INVITRO STUDIES

  • 1 January 1977
    • journal article
    • research article
    • Vol. 5  (2) , 198-204
Abstract
Trihalomethanes (haloforms) were metabolized to CO by a rat liver microsomal fraction requiring both NADPH and molecular O2 for maximal activity. GSH [glutathione] alone did not serve as a cofactor; GSH in the presence of NADPH and O2 produced an 8-fold increase in the metabolism of bromoform to CO. Similar results were obtained with other sulfhydryl compounds. The biotransformation of bromoform to CO was characterized with respect to time course, microsomal protein concentration, pH and temperature. The metabolism of haloforms to CO followed the halide order; iodoform yielded the greatest amount of CO, whereas chloroform yielded the smallest amount. A Km of 6.78 .+-. 2.71 mM was established for bromoform and the Vmax was 1.09 .+-. 0.19 nmol of CO/mg of microsomal protein per min. The energy of activation for this reaction was 6.5 .+-. 0.18 kcal/mol. Cytochrome P-450 was found to bind bromoform to produce a type I binding spectrum. Treatment of rats with phenobarbital or 3-methylcholanthrene increased the rate of conversion of bromoform to CO. Cobaltous chloride treatment of rats or storage of microsomal preparations at 4.degree. C reduced the rate of formation of CO from bromoform. SKF 525-A inhibited the conversion of bromoform to CO. Haloforms may be metabolized to CO via a cytochrome P-450-dependent mixed-function oxidase system. [Haloforms are present in drinking water due to chlorination.].

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