Utilization and metabolism of methyl-sterol derivatives in the yeast mutant strain GL7

Sterols modified at various positions of the tetracyclic nucleus were tested as growth supplements for Saccharomyces cerevisiae strain GL7 erg12 heme3. Derivatives of 3 beta-cholestanol or delta 7-3 beta-cholestenol bearing either a single alpha-oriented methyl group of a gem-dimethyl group at C-4 supported the growth of the mutant whereas 4 beta-methyl sterols did not. The nutritionally active alkyl derivatives were metabolized to 4-demethyl sterols while 4 beta-methyl derivatives were incorporated unchanged, indicating that the C-4 demethylase of yeast is specific for alpha-oriented methyl groups. It appears that 4-demethyl sterols are obligatory for growth of this organism. C-4 methyl derivatives of cholesterol did not support growth, suggesting that the delta 5 double bond blocks demethylation at the adjacent C-4. In other experiments, 14 alpha-methyl sterols were effective growth supplements, while 3 alpha-methylcholesterol was totally inactive. Removal of the C-19 methyl group of cholesterol (19-noncholesterol) rendered the sterol somewhat less effective as a sterol source. The sterol specificity for yeast appears to be particularly strict with regard to substituents that add bulk to the A ring of the steroid nucleus.