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DOI: 10.1055/s-0031-1298155
© Georg Thieme Verlag KG Stuttgart · New York
Terpene Alcohols Inhibit De Novo Sphingolipid Biosynthesis
Publikationsverlauf
received October 13, 2011
revised Dec. 14, 2011
accepted Dec. 15, 2011
Publikationsdatum:
24. Januar 2012 (online)
![](https://www.thieme-connect.de/media/plantamedica/201205/lookinside/thumbnails/10.1055-s-0031-1298155-1.jpg)
Abstract
The terpene alcohols geranyllinalool, phytol (diterpene alcohol), and farnesol (sesquiterpene alcohol) were newly found to inhibit sphingolipid de novo biosynthesis in LLC-PK1 cells (pig kidney epithelial cells). A simple chromatographic bioassay was established for the screening of inhibitory compounds able to reduce the amount of sphinganine, an intermediate metabolite of sphingolipid biosynthesis. The screening strategy was based on the degree of suppression of fumonisin B1 (FB1)-induced sphinganine accumulation following co-treatment with selected terpene alcohols. L-cycloserine and ISP-1, specific serine palmitoyltransferase (SPT) inhibitors, were used as positive controls. Our results show that measuring reduced sphinganine levels after treatment with 2 µM FB1 in combination with the putative inhibitory compounds provides a useful screening bioassay for evaluating compounds causing sphingolipid depletion. Intracellular sphinganine concentrations were analyzed using the fluorescent peak areas of the o-phthalaldehyde (OPA) derivatives of sphinganine eluted with 87 % acetonitrile on a reversed-phase column. Geranyllinalool, phytol, and farnesol were identified as novel SPT inhibitors that reduce FB1-induced sphinganine accumulation and thus inhibit the first step of sphingolipid de novo synthesis.
Key words
terpene alcohol - geranyllinalool - phytol - sphinganine - fumonisin B1 - ISP-1
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Prof. Yong-Moon Lee
College of Pharmacy and MRC
Chungbuk National University
San 48, Kaesin-Dong, Hungduk-Ku
Chongju 361-763
Korea
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