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Biochem Biophys Res Commun ; 293(1): 1-6, 2002 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-12054554

RESUMO

Farnesol and the related isoprenoids, geranylgeraniol, geranylgeranyl pyrophosphate, and farnesyl pyrophosphate, are produced in the endoplasmic reticulum of hepatocytes in mammals, and each serve important biological functions. Of these compounds, only farnesol was shown to significantly inhibit rabbit liver microsomal cytochrome P450 enzymes. The observed inhibition appeared to be reversible, and was not strictly competitive, but rather mixed in nature. Of the activities examined, ethoxycoumarin de-ethylase and diclofenac-4-hydroxylase activities were most sensitive to farnesol, with K(I) and K(I)' values between 11 and 40 microM. Caffeine-8-hydroxylation and taxol-6-hydroxylation were not inhibited at all by farnesol. Farnesol appeared to be a P450 substrate, as well as an inhibitor, as indicated by the NADPH-dependent decrease in farnesol concentration in microsomal incubations, and the metabolism was inhibited by CO, which pointed to the involvement of P450 isozymes.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Inibidores Enzimáticos/farmacologia , Farneseno Álcool/farmacologia , Microssomos Hepáticos/enzimologia , Animais , Inibidores das Enzimas do Citocromo P-450 , Diterpenos/farmacologia , Farneseno Álcool/farmacocinética , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Cinética , Coelhos , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/metabolismo , Especificidade por Substrato
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