Mass spectrometric analysis of ceramide perturbations in brain and fibroblasts of mice and human patients with peroxisomal disorders

Rapid Commun Mass Spectrom. 2004;18(14):1569-74. doi: 10.1002/rcm.1520.


In this study, the levels and composition of ceramides in brains of newborn mice lacking peroxisomes (Pex5-/-, Zellweger mice) were analyzed using normal-phase high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (HPLC/APCI-MS). Total ceramide compositions were found to be comparable to that of control animals. However, a minor ceramide species, containing hexacosanoic/hexacosenoic acid as the amide fatty acid, was 9-fold increased. Also, in the sphingomyelin-derived ceramides this species was elevated. Subsequent analysis of extracts from fibroblasts of Pex5-/- mice and mice with a defective peroxisomal beta-oxidation (lacking D-specific multifunctional protein 2 (MFP2)), revealed, again, a similar rise in this particular ceramide. Further, this ceramide was elevated in human X-ALD fibroblasts as well. Whether C26:1/0-ceramide is linked to some of the pathology seen in Zellweger syndrome remains to be investigated. However, an increase in this sphingolipid can be considered as a diagnostic criterion for diseases caused by defects in peroxisome biogenesis or peroxisomal beta-oxidation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / metabolism*
  • Brain / pathology
  • Brain Chemistry
  • Ceramides / analysis
  • Ceramides / metabolism*
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Fibroblasts / chemistry
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Humans
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Peroxisomes / metabolism*
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Zellweger Syndrome / genetics
  • Zellweger Syndrome / metabolism*
  • Zellweger Syndrome / pathology


  • Ceramides