Abstract
The inhibitory effect of dicoumarol on the mixed function oxidase system of liver microsomes from phenobarbital treated rats were studied. Lineweaver-Burk plots of p-nitroanisole O-demethylation were non-linear in the presence of dicoumarol but linear in its absence. At high concentrations of p-nitroanisole the inhibition was partially overcome indicating a competition between the substrate and dicoumarol for the enzyme. Furthermore, it was found that dicoumarol promotes a time and concentration dependent conversion of cytochrome P-450 to P-420 and that it inhibits cytochrome P-450 reduction. While these fenomena seem directly related to the inhibitory action of dicoumarol on the overall p-nitroanisole demethylase reaction, an inhibitory effect of dicoumarol on NADH : ferricyanide reductase, on the contrary, was shown not to be related to the inhibition of the demethylation process.
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