DNA and cholesterol biosynthesis in synchronized embryonic rat fibroblasts: I. Temporal relationships between HMG-CoA reductase activity,sterol biosynthesis and thymidine incorporation into DNA

Temporal relationships between hydroxymethylglutaryl-CoA reductase activity, biosynthesis of C₂₇ sterols, and [³H]thymidine incorporation into DNA were studied in a rat embryo fibroblast cell line synchronized by double thymidine block and cultured in cholesterol-containing medium. Cyclic variations of HMG-CoA reductase activity and C₂₇ sterols occurred, with two maxima in S and G₂M phases; the relative shortness of the G₁ phase (3 h) in these cells could be responsible for the shift of sterol synthesis in the S phase. No noticeable variation of the individual C₂₇ sterols was observed during the entire cell cycle. In each experiment, there was a good linear correlation between HMG-CoA reductase activity and C₂₇ sterol synthesis, but from one experiment to another, a given level of enzymatic activity led to varying levels of [2-¹⁴C]acetate incorporation into sterols. In our experimental conditions, total HMG-CoA reductase activity is measured, and the preceding observation could be explained by a varying degree of phosphorylation of the enzyme depending on the metabolic state of the cells at the start of the experiment. The cyclic variations of the enzyme activity seem to be due more to increased synthesis at given times of the cycle than to periodic dephosphorylation. We question the existence of a relationship between cell division and cyclic sterol synthesis occurring in cells cultured in cholesterol-containing medium.     

Inhibition of ergosterol biosynthesis in saccharomyces cerevisiae and Ustilago maydis by tridemorph,fenpropimorph and fenpropidin

The structurally related fungicides, tridemorph, fenpropimorph and fenpropidin have been shown to inhibit the sterol Δ¹⁴-reductase and Δ⁸→Δ⁷-isomerase during ergosterol biosynthesis in Saccharomyces cerevisiae and Ustilago maydis. However, although the three fungicides are able to inhibit both enzymes, tridemorph inhibits the Δ⁸-Δ⁷-isomerase better than the Δ¹⁴-reductase whilst the reverse is true for fenpropidin and to a lesser extent for fenpropimorph.