Biodiversity of sphingoid bases in a relationship

Sphingolipid - Wikipedia

Jul 24, bases. To explore these structure-function relationships further, erythro- and All of these analogs inhibit the acylation of sphingoid bases by. Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols. Loncharich RJ () Relationship between structure and biological activity of. The long chain bases of sphingomyelin from Morris hepatoma and host .. Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols.

To characterize further the properties of the AP1 backbone, a series of 2-aminohydroxy- and 3, 5-dihydroxy- octadecanes have been synthesized, and this report describes the somewhat unexpected finding that these analogs not only inhibit ceramide synthase but also serve as alternative substrates.

Because these findings indicated that the aminopentol backbone of fumonisins may be acylated by ceramide synthase, the formation of N-palmitoyl-AP1 PAP1 was also characterized.

Finally, PAP1was found to be highly toxic for HT29 cells, apparently as a new category of ceramide synthase inhibitor. To detect fumonisins, the plates were sprayed with a 0. The clean-up was carried out by extraction with n-butanol as described for the ceramide synthase assay of FB1 see below. The reaction was checked by TLC as described above. The reaction mixture 0.

Acylation of Naturally Occurring and Synthetic 1-Deoxysphinganines by Ceramide Synthase

Assays of Ceramide Synthase Ceramide synthase was assayed as described by Merrill and Wang 24 by following either acylation of [3H]sphingosine to ceramide for inhibition studies or acylation of the sphingoid base analog using a radiolabeled fatty acyl-CoA.

The reaction mixture was vortexed, approximately 3 ml of slightly basic water was added, and the mixture was vortexed again. The CHCl3 layer was washed, dried, and evaporated as described above. The reaction mixture was vortexed, centrifuged, and the CHCl3 layer was again washed with slightly basic water, dried, evaporated, and analyzed by TLC.

The aqueous phase was acidified to pH 4—5 by adding 0. After the plates were developed and air dried, the products were visualized by spraying with p-anisaldehyde solution, and the radiolabeled regions of the plate were detected using a Bioscan System Image Scanner Bioscan Inc. The regions that migrated coincident with the standards were collected and counted using a detergent-containing scintillation mixture for 10 min in a Beckmann LS scintillation counter Beckman Instruments, Palo Alto, CA.

  • Sphingolipid
  • Biodiversity of sphingoid bases ("sphingosines") and related amino alcohols.

After 24 h, the cells were harvested with 0. Complex sphingolipids may be formed by addition of head groups to ceramide or phytoceramide: Sphingomyelins have a phosphocholine or phosphoethanolamine molecule with an ester linkage to the 1-hydroxy group of a ceramide.

Cerebrosides have a single glucose or galactose at the 1-hydroxy position. Sulfatides are sulfated cerebrosides. Gangliosides have at least three sugars, one of which must be sialic acid. Inositol -containing ceramides, which are derived from phytoceramide, are produced in yeast. These include inositol phosphorylceramide, mannose inositol phosphorylceramide, and mannose diinositol phosphorylceramide.

Mammalian sphingolipid metabolism[ edit ] De novo sphingolipid synthesis begins with formation of 3-keto-dihydrosphingosine by serine palmitoyltransferase. However, studies have demonstrated that serine palmitoyltransferase has some activity toward other species of fatty acyl-CoA [8] and alternative amino acids[9] and the diversity of sphingoid bases has recently been reviewed.

Dihydrosphingosine is acylated by a dihydro -ceramide synthase, such as Lass1p or Lass2p also termed as CerSto form dihydroceramide.

Naturally Occuring Shpingolipids and Spingolipid Analogs - Alfred Merrill

Sphingolipidoses are labeled at corresponding stages that are deficient. Ceramide may subsequently have several fates. It may be phosphorylated by ceramide kinase to form ceramidephosphate. Alternatively, it may be glycosylated by glucosylceramide synthase or galactosylceramide synthase. Additionally, it can be converted to sphingomyelin by the addition of a phosphorylcholine headgroup by sphingomyelin synthase.

Diacylglycerol is generated by this process. Finally, ceramide may be broken down by a ceramidase to form sphingosine. Sphingosine may be phosphorylated to form sphingosinephosphate. This may be dephosphorylated to reform sphingosine. The complex glycosphingolipids are hydrolyzed to glucosylceramide and galactosylceramide.