TY - JOUR
T1 - Comparative studies of metabolism of 4-desmethyl, 4-monomethyl and 4,4-dimethyl sterols in Manduca sexta
AU - Svoboda, James A.
AU - Ross, Samir A.
AU - Nes, W. David
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 1995/1
Y1 - 1995/1
N2 - To investigate the metabolism and possible deleterious effects of 4-methyl and 4,4-dimethyl steroids in Manduca sexta, the 4,4-dimethyl sterols lanosterol and cycloartenol, the 4-methyl sterol obtusifoliol and the 4,4-dimethyl pentacyclic triterpenoid α-amyrin were fed in an artificial agar-based diet at various concentrations. Utilization and metabolism of these four compounds were compared with sitosterol, stigmasterol, brassicasterol, ergosterol and 24-methylenecholesterol, 24-alkyl sterols that are readily dealkylated and converted to cholesterol in Manduca and in most phytophagous insects. None of the 4-methylated compounds significantly inhibited development except at very high dietary concentrations. The Δ24-bonds of lanosterol and cycloartenol were effectively reduced by the Manduca Δ24-sterol reductase enzyme, as is the Δ24-bond of desmosterol which, in most phytophagous insects, is an intermediate in the conversion of sitosterol, stigmasterol and other C28 and C29 phytosterols to cholesterol. On the other hand, the 24-methylene substituent of obtusifoliol was not dealkylated. Each of the 4-desmethyl C28 and C29 sterols was readily converted to cholesterol, and a significant amount of 7-dehydro-cholesterol was derived from ergosterol metabolism. The reason for the differences in substrate specificity of these sterols is not clear, but the information may be useful in the development of new, specific, mechanism-based inhibitors of sterol metabolism.
AB - To investigate the metabolism and possible deleterious effects of 4-methyl and 4,4-dimethyl steroids in Manduca sexta, the 4,4-dimethyl sterols lanosterol and cycloartenol, the 4-methyl sterol obtusifoliol and the 4,4-dimethyl pentacyclic triterpenoid α-amyrin were fed in an artificial agar-based diet at various concentrations. Utilization and metabolism of these four compounds were compared with sitosterol, stigmasterol, brassicasterol, ergosterol and 24-methylenecholesterol, 24-alkyl sterols that are readily dealkylated and converted to cholesterol in Manduca and in most phytophagous insects. None of the 4-methylated compounds significantly inhibited development except at very high dietary concentrations. The Δ24-bonds of lanosterol and cycloartenol were effectively reduced by the Manduca Δ24-sterol reductase enzyme, as is the Δ24-bond of desmosterol which, in most phytophagous insects, is an intermediate in the conversion of sitosterol, stigmasterol and other C28 and C29 phytosterols to cholesterol. On the other hand, the 24-methylene substituent of obtusifoliol was not dealkylated. Each of the 4-desmethyl C28 and C29 sterols was readily converted to cholesterol, and a significant amount of 7-dehydro-cholesterol was derived from ergosterol metabolism. The reason for the differences in substrate specificity of these sterols is not clear, but the information may be useful in the development of new, specific, mechanism-based inhibitors of sterol metabolism.
UR - http://www.scopus.com/inward/record.url?scp=0028804619&partnerID=8YFLogxK
U2 - 10.1007/BF02537047
DO - 10.1007/BF02537047
M3 - Article
C2 - 7760694
AN - SCOPUS:0028804619
VL - 30
SP - 91
EP - 94
JO - Lipids
JF - Lipids
SN - 0024-4201
IS - 1
ER -