Different rates of flux through the biosynthetic pathway for long-chain versus very-long-chain sphingolipids

Iris D. Zelnik, Giora Volpert, Leena E. Viiri, Dimple Kauhanen, Tamar Arazi, Katriina Aalto-Setälä, Reijo Laaksonen, Anthony H. Futerman

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)

Abstract

The backbone of all sphingolipids (SLs) is a sphingoid long-chain base (LCB) to which a fatty acid is N-acylated. Considerable variability exists in the chain length and degree of saturation of both of these hydrophobic chains, and recent work has implicated ceramides with different LCBs and N-acyl chains in distinct biological processes; moreover, they may play different roles in disease states and possibly even act as prognostic markers. We now demonstrate that the halflife, or turnover rate, of ceramides containing diverse N-acyl chains is different. By means of a pulse-labeling protocol using stable-isotope, deuterated free fatty acids, and following their incorporation into ceramide and downstream SLs, we show that very-long-chain (VLC) ceramides containing C24:0 or C24:1 fatty acids turn over much more rapidly than longchain (LC) ceramides containing C16:0 or C18:0 fatty acids due to the more rapid metabolism of the former into VLC sphingomyelin and VLC hexosylceramide. In contrast, d16:1 and d18:1 ceramides show similar rates of turnover, indicating that the length of the sphingoid LCB does not influence the flux of ceramides through the biosynthetic pathway. Together, these data demonstrate that the N-acyl chain length of SLs may not only affect membrane biophysical properties but also influence the rate of metabolism of SLs so as to regulate their levels and perhaps their biological functions.

Original languageEnglish
Pages (from-to)1341-1346
Number of pages6
JournalJournal of Lipid Research
Volume61
Issue number10
DOIs
Publication statusPublished - Oct 2020
Publication typeA1 Journal article-refereed

Keywords

  • Ceramide
  • Fatty acids
  • Hexosylceramide
  • Lipid metabolism
  • Lipidomics
  • Sphingomyelin
  • Stable isotopes
  • Turnover

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Fingerprint Dive into the research topics of 'Different rates of flux through the biosynthetic pathway for long-chain versus very-long-chain sphingolipids'. Together they form a unique fingerprint.

Cite this