Inhibition of the biosynthesis of sterols by phenyl and phenolic compounds in rat liver.
The presence of mitochondria increased the incorporation of [2-(14)C]mevalonate into sterols in a cell-free system from rat liver. Various phenyl and phenolic compounds inhibited the incorporation of mevalonate when added in vitro. p-Hydroxycinnamate, a metabolite of tyrosine, was the most powerful inhibitor among the compounds tested. Catechol, resorcinol and quinol were inhibitory at high concentrations. Organic acids lacking an aromatic ring were not inhibitory. Two hypocholesterolaemic drugs, Clofibrate (alpha-p-chlorophenoxyisobutyrate) and Clofenapate [alpha,4-(p-chlorophenyl)phenoxyisobutyrate], which are known to affect some step before the formation of mevalonate in the biosynthesis of cholesterol in vivo, showed inhibition at a step beyond the formation of mevalonate in vitro. The presence of the aromatic ring and the carboxyl group in a molecule appears to be necessary for the inhibition.
D000255:Adenosine Triphosphate / Q000008:administration & dosage; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D002396:Catechols / Q000494:pharmacology; D002474:Cell-Free System; D002934:Cinnamates / Q000494:pharmacology; D002951:Citrates / Q000494:pharmacology; D002994:Clofibrate / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects*; D008293:Malates / Q000494:pharmacology; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D010071:Oxaloacetates / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D012118:Resorcinols / Q000494:pharmacology; D013261:Sterols / Q000096:biosynthesis*
D001713:Biphenyl Compounds; D002087:Butyrates; D002250:Carbon Radioisotopes; D002396:Catechols; D002934:Cinnamates; D002951:Citrates; D004987:Ethers; D008293:Malates; D010071:Oxaloacetates; D010636:Phenols; D012118:Resorcinols; D013261:Sterols; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D002994:Clofibrate; D008798:Mevalonic Acid