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Title: INHIBITION OF STEROL METABOLISM IN CAENORHABDITIS ELEGANS BY AY-9944

Author
item Chitwood, David

Submitted to: International Congress of Nematology
Publication Type: Abstract Only
Publication Acceptance Date: 4/2/2002
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Caenorhabditis elegans and some other nematodes are capable of attaching a methyl group to the nucleus of sterols at the C-4 position. In C. elegans, 4-methylcholest-8(14)-enol is the most abundant 4-methylsterol produced, and smaller quantities of 4-methylcholest-7-enol also occur. The purpose of this study was to treat C. elegans with a known inhibitor of steroid C-7 double bond isomerization in order to more fully understand the pathway of 4-methylsterol formation. Thus, C. elegans was propagated in sterile semidefined medium with or without 50 mg/L AY-9944. The media were supplemented with sitosterol as a dietary sterol. Lipids were extracted from the nematodes and saponified; sterols were isolated with column chromatography and identified with gas chromatography. The sterols of inhibitor-untreated nematodes contained 91.4% 4-desmethylsterol plus 8.6% 4-methylsterol; the inhibitor-treated nematode sterol contained only 4.6% 4-methylsterol. The 4-methylcholest-8(14)-enol:lophenol ratio in control nematodes was 9.75 but only 0.71 in treated nematodes. The results are consistent with a pathway involving the methylation of cholest-7-enol to form lophenol as an intermediate in the production of the final product of the methylation pathway, 4-methylcholest-8(14)-enol.