Topic
Lanosterol
About: Lanosterol is a research topic. Over the lifetime, 1239 publications have been published within this topic receiving 36737 citations. The topic is also known as: (3β)-lanosta-8,24-dien-3-ol & (3β,20R)-lanosta-8,24-dien-3-ol.
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TL;DR: The P. carinii S-adenosyl-L-methionine:sterol C-24 methyl transferase (SAM:SMT) has unique properties; it prefers lanosterol as its sterol substrate.
17 citations
01 Jan 1990
TL;DR: Two new azasqualenoid derivatives, bearing a 22,23 epoxidic function, were synthesized, to obtain more efficient, competitive inhibitors of the enzyme squalene 2,3-oxide-lanosterol cyclase, and a new hypothesis is suggested.
Abstract: Two new azasqualenoid derivatives, bearing a 22,23 epoxidic function, were synthesized, to obtain more efficient, competitive inhibitors of the enzyme squalene 2,3-oxide-lanosterol cyclase (EC 5.4.99.7). The activities of 22,23-epoxy-2-aza-2,3-dihydrosqualene 4 and of its N-oxide derivative 5 were studied using rat and pig liver microsomal preparations and compared with a pig liver partially purified squalene 2,3-oxide-lanosterol cyclase. The activities of compounds 4 and 5 were compared in the different enzymatic preparations with the activities of 2-aza-2,3-dihydrosqualene 2 and of 2-aza-2,3-dihydrosqualene N-oxide 3 previously studied only with rat liver microsomes. Using a solubilized, partially purified squalene 2,3-oxide cyclase, all the compounds exhibited a non-competitive type of inhibition. As the previously suggested mechanism of inhibition does not account for this kinetic behaviour, a new hypothesis is suggested.
17 citations
TL;DR: Z protein may modulate several microsomal enzymic activities of sterol biosynthesis in concert by exhibiting affinities for the membrane as well as low-molecular-weight cofactors, substrates, and metabolic effectors.
17 citations
TL;DR: In this article, the effects of alpha-demethylase inhibitors, such as ketoconazole and miconazole, on low-density lipoprotein suppression of reductase activity were investigated in rat intestinal epithelial cells.
16 citations
TL;DR: Kinetic studies showed that the inhibition pattern was dependent only on whether the side chains on the 8-azadecalin were linear or branched; the compounds having isoprenoid-like chains were non-competitive inhibitors, while those having linear hydrocarbon chains (amides or amines) were competitive inhibitors.
Abstract: The inhibitors of 2,3-oxidosqualene:lanosterol cyclase were investigated by comparative studies between pig's liver and Baker's yeast. The fundamental skeleton of the inhibitors was 8-azadecalin. To the nitrogen atom, an isoprenoid-like chain [nerylacetone (Z-form), geranylacetone (E-form) or its hydrogenated form] was attached by the reaction of reductive amination with NaCNBH3. Among the three forms, the Z-isomer was the most potent inhibitors toward both the pig's liver and yeast cyclases. To examine the effect of carbon chain length (lipophilicity), various fatty acids (C6-C18) were appended to the 8-azadecalin derivatives. Strong inhibitory activity was observed for those compounds having carbon chains around C12. Interestingly, the amide compounds (not the carbocationic intermediate) exhibited remarkably strong inhibition toward the liver cyclase, whereas they had an insignificant effect on the yeast cyclase (about 10(2)-fold less active). The yeast cyclase needed the amine functionality (carbocationic intermediate), which was prepared by using LiAlH4 from the corresponding amides, to exhibit potent inhibition. We found that N-dodecyl-8-aza-4,4,10 beta-trimethyl-trans-decal-3 beta-ol (7i) was the most potent inhibitor (IC50 = 1 microM) toward the yeast cyclase amongst any known material. Kinetic studies showed that the inhibition pattern was dependent only on whether the side chains on the 8-azadecalin were linear or branched; the compounds having isoprenoid-like chains were non-competitive inhibitors, while those having linear hydrocarbon chains (amides or amines) were competitive inhibitors.
16 citations