Inhibition of sterol synthesis by delta 5-sterols in a sterol auxotroph of yeast defective in oxidosqualene cyclase and cytochrome P-450.

摘要: Synthesis of ergosterol is demonstrated in the GL7 mutant Saccharomyces cerevisiae. This sterol auxotroph has been thought to lack ability synthesize sterols due both absence 2,3-oxidosqualene cyclase and a heme deficiency eliminating cytochrome P-450 which required demethylation at C-14. However, when medium was 5 alpha-cholestan-3 beta-ol, alpha-cholest-8(14)-en-3 or 24 beta-methyl-5 synthesis found proceed yielding 1-3 fg/cell (24 beta-methylcholesta-5,7,22E-trien-3 beta-ol). Ergosterol identified by mass spectroscopy, gas high performance liquid chromatography, ultraviolet radioactive labeling from [3H]acetate. Except for some cholest-5-en-3 beta-ol (cholesterol) derived stanol two 8(14)-stenols were not significantly metabolized confirming an isomerase migration double bond C-8(14) C-7. Drastic reduction more than 0.06 observed either had C-5, as case cholesterol, could be with such bond. Thus, alpha-cholest-8(9)-en-3 alpha-cholest-7-en-3 (lathosterol) converted cholesta-5,7-dien-3 (7-dehydrocholesterol), presence latter dienol depressed level ergosterol. The most attractive possible explanations our observations assumption genetic compartments sterols, one affected mutations. ability, despite mutations, small amounts act regulate cell cycle may also explain why this can grow aerobically cholesterol (acting bulk membrane role) sole exogenous sterol.