A study of the role of cytochrome b5 in the reductive metabolism of halothane.

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A role of cytochrome b5 in the reductive metabolism of halothane was studied by analysing the formation of 2-chloro-1, 1, 1-trifluoroethane (CTE) and 2-chloro-1, 1-difluoroethylene (CDE), major reduced metabolites of halothane. Rats pretreated with malotilate (maltilate-treated rats) had significantly more cytochrome b5 than the control rats. At the end of 2-hour exposure to 1% halothane in 14% oxygen, the ratio of CDE to CTE in arterial blood was significantly higher in malotilate treated rats. The formation of CDE and the ratio of CDE to CTE were significantly greater in the microsomes of malotilate-treated rats than those in the controls. In a reconstituted system containing cytochrome P-450PB, addition of cytochrome b5 enhanced the formation of CDE and increased the ratio of CDE to CTE. These redults suggested that cytochrome b5 enhances the formation ratio of CDE to CTE by stimulating the supply of second electron to cytochrome P-450, which might reduce the liberation of a free radical intermediate (a precursor of CTE) in the reductive metabolism of halothane.
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