Pharmacological Modulation of Glycosphingolipid Metabolism

Methods Mol Biol. 2018;1804:401-410. doi: 10.1007/978-1-4939-8552-4_19.


The experimental approach to deplete cellular glycosphingolipids (GSLs) with the specific inhibitors of glycosphingolipid biosynthesis has the potential to identify functions of endogenous GSLs. Most GSLs are derived from glucosylceramide (GlcCer). D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) inhibits GIcCer synthase and has been used extensively to study the biological functions of living cells. D-PDMP inhibits mTORC1 activity, which is independent of its inhibitory activity on GlcCer synthase. We also developed an analog of D-PDMP, D-threo-1-phenyl-2-benzyloxycarbonylamino-3-pyrrolidino-1-propanol (D-PBPP) lacking the effect on mTORC1. Here, we summarize the effects of D-PDMP and D-PBPP on the metabolism of GSLs and cell growth.

Keywords: D-PBPP; D-PDMP; Gangliosides; Glucosylceramide (GlcCer) synthase; Glycolsphingolipids; mTORC1.

MeSH terms

  • Animals
  • Cell Line
  • Endosomes / metabolism
  • Enzyme Inhibitors / pharmacology
  • Glucosyltransferases / antagonists & inhibitors
  • Glucosyltransferases / metabolism
  • Glycosphingolipids / metabolism*
  • Lysosomes / metabolism
  • Mice
  • Morpholines / pharmacology*
  • Procyclidine / analogs & derivatives*
  • Procyclidine / pharmacology
  • Ras Homolog Enriched in Brain Protein / metabolism
  • TOR Serine-Threonine Kinases / metabolism


  • 1-phenyl-2-benzyloxycarbonylamino-3-pyrrolidino-1-propanol
  • Enzyme Inhibitors
  • Glycosphingolipids
  • Morpholines
  • Ras Homolog Enriched in Brain Protein
  • Rheb protein, mouse
  • RV 538
  • Procyclidine
  • Glucosyltransferases
  • ceramide glucosyltransferase
  • TOR Serine-Threonine Kinases