Submitted to: Society of Nematology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 8/9/2004
Publication Date: 9/1/2004
Citation: Chitwood, D.J. 2004. Ay-9944 inhibits reproduction and sterol isomerization in caenorhabditis elegans. J. Nematol. 36(3): 312. 2004. Interpretive Summary:
Technical Abstract: Sterol biochemistry is one of the few fundamental biochemical differences between parasitic nematodes and their plant or mammalian hosts. Nematodes possess a sterol nutritional requirement, which results from their inability to biosynthesize sterols de novo. Consequently, nematodes obtain sterols from their hosts or environment and then metabolize them to other sterols better suited to functions within nematodes. AY-9944 is a compound known to inhibit various isomerases involved in the conversion of C-8(9) or C-8(14) double bonds to C-7 double bonds in plants and mammals. In this study, Caenorhabditis elegans was propagated in a semidefined liquid medium; AY-9944 levels ranged from 0 to 100 mg/L. Nematode reproduction was measured after 3 and 7 days; the ED-50 was approximately 50 mg/L. Sterols from control and inhibitor-treated nematodes were then analyzed by gas chromatography. In both cases, the predominant nematode sterol was 7-dehydrocholesterol; substantial amounts of cholesterol and lathosterol also occurred. A striking difference existed in the 4-methylsterol compositions; the ratio of 4-methylsterols with a C-7(8) double bond to those with a C-8(14) double bond was 13 times larger in AY-9944-treated C. elegans than in controls.