Azasterol inhibitors in yeast. Inhibition of the 24-methylene sterol delta24(28)-reductase and delta24-sterol methyltransferase of Saccharomyces cerevisiae by 23-azacholesterol.
The effects of 23-azacholesterol on sterol biosynthesis and growth of Saccharomyces cervisiae were examined. In the presence of 0.2, 0.5, and 1 micron 23-azacholesterol, aerobically-growing yeast produced a nearly constant amount of ergosta-5,7,22,24(28)-tetraenol (approx. 36% of total sterol) and slowly accumulated zymosterol with a concommitant decline in ergosterol synthesis. Growth and total sterol content of yeast cultures treated with 0.2-1 micron 23-azacholesterol were similar to that of the control culture. Yeast cultures treated with 5 and 10 micron 23-azacholesterol produced mostly zymosterol (58-61% of total sterol), while ergosta-5,7,22,24(28)-tetraenol production declined to less than 10% of total sterol. The observed changes in the distribution of sterols in treated cultures are consistent with inhibition of 24-methylene sterol 24(28)-sterol reductase (total inhibition at 1 micron 23-azacholesterol) and of 24-sterol methyltransferase (71% inhibition at 10 micron 23-azacholesterol). Yeast cultures treated with 10 micron 23-azacholesterol were found to contain 4,4-dimethylcholesta-8,14,24-trienol and 4alpha-methylcholesta-8,14,24-trienol, which were isolated and characterized for the first time.
D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004875:Ergosterol / Q000096:biosynthesis; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D008954:Models, Biological; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D013261:Sterols / Q000032:analysis / Q000096:biosynthesis
D013261:Sterols; C017038:23-azacholesterol; D002784:Cholesterol; D010088:Oxidoreductases; D008780:Methyltransferases; D004875:Ergosterol