COMPARATIVE-STUDIES OF METABOLISM OF 4-DESMETHYL, 4-MONOMETHYL AND 4,4-DIMETHYL STEROLS IN MANDUCA-SEXTA

To investigate the metabolism and possible deleterious effects of 4-me thyl and 4,4-dimethyl steroids in Manduca sexta, the 4,4-dimethyl ster ols lanosterol and cycloartenol, the 4-methyl sterol obtusifoliol and the 4,4-dimethyl pentacyclic triterpenoid alpha-amyrin were fed in an artificial agar-based diet at various concentrations. Utilization and metabolism of these four compounds were compared with sitosterol, stig masterol, brassicasterol, ergosterol and 24-methyleneocholesterol, 24- alkyl sterols that are readily dealkylated and converted to cholestero l in Manduca and in most phytophagous insects. None of the 4-methylate d compounds significantly inhibited development except at very high di etary concentrations. The Delta(24)-bonds of lanosterol and cycloarten ol were effectively reduced by the Manduca Delta(24)-sterol reductase enzyme, as is the Delta(24)-bond of desmosterol which, in most phytoph agous insects, is an intermediate in the conversion of sitosterol, sti gmasterol and other C-28 and C-29 phytosterols to cholesterol. On the other hand, the 24-methylene substituent of obtusifoliol was not dealk ylated. Each of the 4-desmethyl C-28 and C-29 sterols was readily conv erted to cholesterol, and a significant amount of 7-dehydro-cholestero l was derived from ergosterol metabolism. The reason for the differenc es in substrate specificity of these sterols is not clear, but the inf ormation may be useful in the development of new, specific, mechanism- based inhibitors of sterol metabolism.