Farnesol as an inhibitor and substrate for rabbit liver microsomal P450 enzymes
Section snippets
Experimental
The compounds farnesol, geranylgeraniol, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate were purchased from Sigma Chemical, as were the substrates diclofenac, taxol, and p-nitrophenol. The standards, 4-hydroxydiclofenac and 6-hydroxytaxol were purchased from Gentest.
Rabbit livers were purchased from Pel-Freez (Rogers, Arkansas) and rabbit liver microsomes were prepared by a variation of a published protocol [16]. Procedures in the current study were identical to the published ones
Results and discussion
In the presence of farnesol, the p-nitrophenol 3-hydroxylation activity of rabbit liver microsomes was reduced in a concentration-dependent manner (Fig. 1). The inhibition was mixed in nature with KI and KI′ values of 90 and , respectively. The inhibition appeared to be reversible as indicated by the fact that pre-incubation of liver microsomes with farnesol and NADPH had no effect on the resulting p-nitrophenol oxidation activity (data not shown). The value obtained for Km in these
Acknowledgements
The work was supported by a University of North Carolina Institute of Nutrition Grant #980160, and the University of North Carolina at Greensboro.
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