, Volume 48, Issue 12, pp 1253–1267 | Cite as

Molecular Species of Phospholipids with Very Long Chain Fatty Acids in Skin Fibroblasts of Zellweger Syndrome

  • Kotaro Hama
  • Toru Nagai
  • Chiho Nishizawa
  • Kazutaka Ikeda
  • Masashi Morita
  • Noriko Satoh
  • Hiroki Nakanishi
  • Tsuneo Imanaka
  • Nobuyuki Shimozawa
  • Ryo Taguchi
  • Keizo Inoue
  • Kazuaki Yokoyama
Original Article


The ratio of C26:0/C22:0 fatty acids in patient lipids is widely accepted as a critical clinical criterion of peroxisomal diseases, such as Zellweger syndrome and X-linked adrenoleukodystrophy (X-ALD). However, phospholipid molecular species with very long chain fatty acids (VLCFA) have not been precisely characterized. In the present study, the structures of such molecules in fibroblasts of Zellweger syndrome and X-ALD were examined using LC–ESI–MS/MS analysis. In fibroblasts from Zellweger patients, a large number of VLCFA-containing molecular species were detected in several phospholipid classes as well as neutral lipids, including triacylglycerol and cholesteryl esters. Among these lipids, phosphatidylcholine showed the most diversity in the structures of VLCFA-containing molecular species. Some VLCFA possessed longer carbon chains and/or larger number of double bonds than C26:0-fatty acid (FA). Similar VLCFA were also found in other phospholipid classes, such as phosphatidylethanolamine and phosphatidylserine. In addition, VLCFA-containing phospholipid species showed some differences among fibroblasts from Zellweger patients. It appears that phospholipids with VLCFA, with or without double bonds, as well as C26:0-FA might affect cellular functions, thus leading to the pathogenesis of peroxisomal diseases, such as Zellweger syndrome and X-ALD.


Zellweger syndrome Very long chain fatty acids Liquid chromatography–electrospray ionization–tandem mass spectrometry Phosphatidylcholine Phosphatidylethanolamine Phosphatidylserine 



ATP-binding cassette protein D1


X-linked adrenoleukodystrophy


Cholesteryl ester


Liquid chromatography–electrospray ionization–tandem mass spectrometry


Mass spectrometry

PtdCho or PC


PtdEtn or PE


PtdGro or PG


PtdIns or PI


PtdSer or PS





Very long chain fatty acid(s)


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Copyright information

© AOCS 2013

Authors and Affiliations

  • Kotaro Hama
    • 1
  • Toru Nagai
    • 1
  • Chiho Nishizawa
    • 1
  • Kazutaka Ikeda
    • 2
    • 6
  • Masashi Morita
    • 3
  • Noriko Satoh
    • 1
  • Hiroki Nakanishi
    • 2
    • 7
  • Tsuneo Imanaka
    • 3
  • Nobuyuki Shimozawa
    • 4
  • Ryo Taguchi
    • 2
    • 5
    • 8
  • Keizo Inoue
    • 1
  • Kazuaki Yokoyama
    • 1
    • 5
  1. 1.Faculty of Pharmaceutical SciencesTeikyo UniversityTokyoJapan
  2. 2.Department of Metabolome, Graduate School of MedicineThe University of TokyoTokyoJapan
  3. 3.Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
  4. 4.Division of Genomic Research, Life Science Research CenterGifu UniversityGifuJapan
  5. 5.CREST, JSTKawaguchiJapan
  6. 6.Institute for Advanced BiosciencesKeio UniversityTsuruokaJapan
  7. 7.Research Center for BiosignalAkita UniversityAkitaJapan
  8. 8.Department of Biomedical Sciences, College of Life and Health SciencesChubu UniversityKasugaiJapan

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