Seo S, Tonda K, Uomori A, Takeda K, Hirata M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Steroids. 1993 Feb;58(2):74-8. doi: 10.1016/0039-128x(93)90056-s.
The inhibitory effect of SSF-109 on cholesterol synthesis in isolated hepatocytes was studied using a radio-high-performance liquid chromatography system, and the results were compared with those of other inhibitors, triparanol and AMO-1618. SSF-109 caused accumulation of two trimethylsterols: lanosterol and 24-dihydrolanosterol. The distribution profile of [2-14C]mevalonate-originated radioactivity in cholesterol, lanosterol, dihydrolanosterol, 2,3-oxidosqualene, and squalene indicates that SSF-109 inhibits the 14 alpha-methyl demethylase activity. Triparanol accumulated the radioactivity of [2-14C]mevalonate in desmosterol and 2,3-oxidosqualene suggesting that triparanol inhibits sterol delta 24-reductase and 2,3-oxidosqualene cyclase. AMO-1618 caused enrichment of the radioisotope from [2-14C]mevalonate in 2,3-oxidosqualene but reduced it in squalene, suggesting that AMO-1618 acts on 2,3-oxidosqualene cyclase and some enzyme that catalizes a metabolic pathway between mevalonate and squalene.
使用放射性高效液相色谱系统研究了SSF - 109对分离的肝细胞中胆固醇合成的抑制作用，并将结果与其他抑制剂三苯乙醇和AMO - 1618的结果进行了比较。SSF - 109导致两种三甲基甾醇（羊毛甾醇和24 - 二氢羊毛甾醇）积累。[2 - 14C]甲羟戊酸来源的放射性在胆固醇、羊毛甾醇、二氢羊毛甾醇、2,3 - 氧化角鲨烯和角鲨烯中的分布情况表明，SSF - 109抑制14α - 甲基脱甲基酶活性。三苯乙醇使[2 - 14C]甲羟戊酸的放射性在链甾醇和2,3 - 氧化角鲨烯中积累，这表明三苯乙醇抑制甾醇δ24 - 还原酶和2,3 - 氧化角鲨烯环化酶。AMO - 1618使2,3 - 氧化角鲨烯中[2 - 14C]甲羟戊酸的放射性同位素富集，但使角鲨烯中的放射性降低，这表明AMO - 1618作用于2,3 - 氧化角鲨烯环化酶以及某种催化甲羟戊酸与角鲨烯之间代谢途径的酶。
