Tabacik C, Aliau S, Sultan C
Biochim Biophys Acta. 1985 Nov 14;837(2):152-62. doi: 10.1016/0005-2760(85)90238-3.
Cholesterol biosynthesis in cultured human skin fibroblasts was studied by [14C]acetic acid incorporation into non-saponifiable lipids and quantification of labeled cholesterol among its precursors. Synthesis was slow, in spite of a high 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA) activity and led to an accumulation of unexpected non-polar metabolites identified as C-30 sterones, but not C-27 sterol precursors. This supports a post-HMG-CoA regulation at the lanosterol demethylation step. Cholesterol biosynthesis was stimulated by cell culture in lipid depleted medium and was inhibited by pentadecane-2-one which acts mainly at two post-HMG-CoA steps: lanosterol demethylation and lathosterol isomerisation to cholesterol. A parallel pentadecane-2-one inhibition of cell growth was also observed, even when cells were cultured in the presence of whole serum. This indicates the existence of a relationship between endogenous cholesterol synthesis and cell growth and sheds additional light on the role of post-HMG-CoA regulation in this phenomenon.
通过将[14C]乙酸掺入非皂化脂质并对其前体中的标记胆固醇进行定量，研究了培养的人皮肤成纤维细胞中的胆固醇生物合成。尽管3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-CoA）活性很高，但合成过程缓慢，并导致了意外的非极性代谢物的积累，这些代谢物被鉴定为C-30甾酮，而非C-27甾醇前体。这支持了在羊毛甾醇去甲基化步骤存在HMG-CoA之后的调节。在脂质缺乏的培养基中进行细胞培养可刺激胆固醇生物合成，而十五烷-2-酮则可抑制胆固醇生物合成，十五烷-2-酮主要作用于HMG-CoA之后的两个步骤：羊毛甾醇去甲基化和羊毛甾醇异构化为胆固醇。即使在全血清存在的情况下培养细胞，也观察到十五烷-2-酮对细胞生长的平行抑制作用。这表明内源性胆固醇合成与细胞生长之间存在关联，并进一步揭示了HMG-CoA之后的调节在这一现象中的作用。
