Ranganathan S, Ramasarma T
Biochem J. 1973 Jul;134(3):737-43. doi: 10.1042/bj1340737.
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.
线粒体的存在增加了[2-(14)C]甲羟戊酸在大鼠肝脏无细胞体系中掺入甾醇的量。各种苯基和酚类化合物在体外添加时会抑制甲羟戊酸的掺入。对羟基肉桂酸是酪氨酸的一种代谢产物，在所测试的化合物中是最有效的抑制剂。儿茶酚、间苯二酚和对苯二酚在高浓度时具有抑制作用。缺乏芳香环的有机酸没有抑制作用。两种降血脂药物，氯贝丁酯（α-p-氯苯氧基异丁酸酯）和氯苯那酯[α,4-(p-氯苯基)苯氧基异丁酸酯]，已知它们在体内胆固醇生物合成中会影响甲羟戊酸形成之前的某个步骤，但在体外却在甲羟戊酸形成之后的步骤表现出抑制作用。分子中芳香环和羧基的存在似乎是产生抑制作用所必需的。
