Studies of the action of ceramide-like substances (D- and L-PDMP) on sphingolipid glycosyltransferases and purified lactosylceramide synthase

Subroto Chatterjee, Tavia Cleveland, Wan Yang Shi, Jin Ichi Inokuchi, Norman S. Radin

Research output: Contribution to journalArticle

Abstract

We have studied the effects of D-threo-1-phenyl-2-decanoylamino-3- morpholino-1-propanol (D-PDMP) and its L-enantiomer on glycosphingolipids in cultured normal human kidney proximal tubular cells. We found that D-PDMP exerted a concentration-dependent reduction in the metabolic labelling and cellular levels of glucosylceramide (GlcCer), lactosylceramide (LacCer), and the globo-series glycosphingolipids, GbOse3Cer and GbOse4Cer. It also directly inhibited the activity of UDP-glucose:ceramide β1 → 4- glucosyltransferase (GlcT-1) and UDP-galactose: GlcCer β1 → 4 galactosyltransferase (GalT-2). In contrast, L-PDMP had opposite effects on the metabolic labelling of GlcCer, LacCer, and GbOse3Cer. The levels of GlcCer and LacCer were increased, while the labelling and level of GbOse4Cer were strongly reduced. Purified GalT-2 from human kidney was inhibited by D- PDMP and stimulated by L-PDMP. It appears likely that the different glycosphingolipid glycosyltransferases possess similar binding sites for the ceramide moiety, which are blocked by binding to D-PDMP and, in the case of GbOse4Cer synthase, by L-PDMP as well. The stimulatory effects of L-PDMP on GlcCer and LacCer synthases may be the result of binding to a modulatory site on the glycosyltransferases; in intact cells, the enzyme-analog complex may afford protection against the normal catabolic inactivation of the enzymes.

Original languageEnglish (US)
Pages (from-to)481-486
Number of pages6
JournalGlycoconjugate Journal
Volume13
Issue number3
DOIs
StatePublished - Jun 24 1996

Keywords

  • PDMP (1-phenyl-2-decanoylamino-3-morpholino-1- propanol)
  • globotetrao sylceramide
  • globotriaosylceramide
  • glucosylceramide
  • inhibition and stimulation by PDMP enantiomers
  • lactosylceramide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Studies of the action of ceramide-like substances (D- and L-PDMP) on sphingolipid glycosyltransferases and purified lactosylceramide synthase'. Together they form a unique fingerprint.

  • Cite this