Biochemistry and function of nematode steroids

Compared to other organisms, nematodes have been the subject of relatively few investigations into their steroid biochemistry. Nutritional experiments have clearly demonstrated a dietary requirement for sterol that results from the inability of nematodes to biosynthesize steroids de novo. Although the specificity of the nutritional requirement varies somewhat among nematodes, most 4-desmethysterols can be directly utilized by nematodes or else metabolized to sterols better suited for nematode growth and development. Much knowledge has been obtained about the abilities of microbivorous nematodes to metabolize sterols. Various species can remove ethyl and methyl substitutes at C-24, introduce double bonds at C-7, C-23, and C-24(28), reduce Δ5-, Δ22, and Δ24-bonds, isomerize Δ7 to Δ8(14)-bonds, esterify fatty acids at C-3, and directly methylate the sterol nucleus at C-4 by a process unique to nematodes. Moreover, azasteroids and structurally related alkylamines and alkylamides inhibit the activity of nematode Δ24-sterol reductase and also disrupt the life cycles of these species as well as parasitic species. Less is known, however, about sterol metabolism in parasitic nematodes because of the inability to culture them apart from their hosts. Most plant-parasitic nematodes appear to dealkylate plant sterols at C-24 and modify the sterols nucleus, particularly by reduction of Δ5-bonds. Sterols metabolism in mammalian parasites has been studied to a very limited extent only. Except for a structural presence of sterols in membranes of nematodes, the function of these compounds in nematodes is poorly understood. Although nematodes do contain steroids that have hormonal functions in other organisms, attempts to demonstrate endogenous biosynthesis of these steroids by nematodes have been unsuccessful and elucidation of the function of these compounds within nematodes warrants immediate investigation. Other area of nematode steroid biochemistry requiring further research include investigation of the metabolism of sterols by vertebrate-parasitic nematodes, the purification and characterization of enzymes involved in nematode steroid metabolism, evaluation of a broader array of steroid biosynthesis inhibitors upon nematodes, and elucidation of the specific metabolic steps and the function of the 4-methylation pathway. Because C. elegans will be the first animal whose entire genome is sequenced, additional questions will be raised by the discovery of genes with sequences similar to those for steroid biosynthesis enzymes or receptors. All of these research fronts could accelerate the development of novel means for controlling parasitic nematodes.