Inhibition of C28 and C29 phytosterol metabolism by N,N-dimethyldodecanamine in the nematode Caenorhabditis elegans.
Effects on the metabolism of campesterol and stigmasterol in Caenorhabditis elegans were investigated using N,N-dimethyldodecanamine, a known inhibitor of growth, reproduction and the delta 24-sterol reductase of this nematode. 7-Dehydrocholesterol was the predominant sterol (51%) of C. elegans grown in stigmasterol-supplemented media, whereas addition of 25 ppm amine resulted in a large decrease in the relative percentage of 7-dehydrocholesterol (23%) and the accumulation of a substantial proportion (33%) of delta 24-sterols (e.g., cholesta-5,7,24-trienol) and delta 22,24-sterols (e.g., cholesta-5,7,22, 24-tetraenol) but yielded no delta 22-sterols. Dealkylation of stigmasterol by C. elegans proceeded in the presence of the delta 22-bond; reduction of the delta 22-bond occurred prior to delta 24-reduction. Addition of 25 ppm amine to campesterol-supplemented media altered the sterol composition of C. elegans by increasing the percentage of unmetabolized dietary campesterol from 39 to 60%, decreasing the percentage of 7-dehydrocholesterol from 26 to 12%, and causing the accumulation of several delta 24-sterols (6%). C. elegans also was shown to be capable of dealkylating a delta 24 (28)-sterol as it converted 24-methylenecholesterol to mostly 7-dehydrocholesterol. The proposed role of 24-methylenecholesterol as an intermediate between campesterol and 7-dehydrocholesterol was supported by the results.
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D002107:Caenorhabditis / Q000187:drug effects / Q000378:metabolism*; D013058:Mass Spectrometry; D010840:Phytosterols / Q000378:metabolism*; D013261:Sterols / Q000096:biosynthesis; D013265:Stigmasterol / Q000378:metabolism; D013324:Strontium
D000588:Amines; D010840:Phytosterols; D013261:Sterols; C036252:N,N-dimethyl-1-dodecanamine; D013265:Stigmasterol; D013324:Strontium