title: Terpene alcohols inhibit de novo sphingolipid biosynthesis.
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.
authors.affiliation: College of Pharmacy and MRC, Chungbuk National University, Chongju, Korea.
authors.forename: Kyong-Oh
authors.initials: KO
authors.lastname: Shin
authors.forename: Myong-Yong
authors.initials: MY
authors.lastname: Park
authors.forename: Cho-Hee
authors.initials: CH
authors.lastname: Seo
authors.forename: Yong-Ill
authors.initials: YI
authors.lastname: Lee
authors.forename: Hyun Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Hwan-Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Jung
authors.forename: Yong-Moon
authors.initials: YM
authors.lastname: Lee
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D001681:Biological Assay; D003523:Cycloserine / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D004357:Drug Synergism; D005204:Farnesol / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D037341:Fumonisins / Q000494:pharmacology*; D006801:Humans; D018374:LLC-PK1 Cells; D015394:Molecular Structure; D010836:Phytol / Q000494:pharmacology; D013107:Sphingolipids / Q000096:biosynthesis*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D013552:Swine; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D000080462:Acyclic Monoterpenes; D004224:Diterpenes; D005229:Fatty Acids, Monounsaturated; D037341:Fumonisins; D013107:Sphingolipids; D013729:Terpenes; D010836:Phytol; C056933:fumonisin B1; D005204:Farnesol; D003523:Cycloserine; D013110:Sphingosine; C005682:safingol; C534312:3,7,11,15-tetramethyl-1,6,10,14-hexadecatetraen-3-ol; C001996:thermozymocidin