Abnormal fatty alcohol metabolism in cultured keratinocytes from patients with Sjögren-Larsson syndrome

William B Rizzo, Debra A. Craft, Tara Somer, Gael Carney, Juliana Trafrova, Marcia Simon

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder characterized by ichthyosis, mental retardation, spasticity, and deficient activity of fatty aldehyde dehydrogenase (FALDH). FALDH is an enzyme component of fatty alcohol:NAD oxidoreductase (FAO), which is necessary for fatty alcohol metabolism. To better understand the biochemical basis for the cutaneous symptoms in this disease, we investigated lipid metabolism in cultured keratinocytes from SLS patients. Enzyme activities of FALDH and FAO in SLS cells were <10% of normal. SLS keratinocytes accumulated 45-fold more fatty alcohol (hexadecanol, octadecanol, and octadecenol) than normal, whereas wax esters and 1-O-alkyl-2,3-diacylglycerols were increased by 5.6-fold and 7.5-fold, respectively. SLS keratinocytes showed a reduced incorporation of radioactive octadecanol into fatty acid (24% of normal) and triglyceride (13% of normal), but incorporation into wax esters and 1-O-alkyl-2,3-diacylglycerol was increased by 2.5-fold and 2.8-fold, respectively. Our results indicate that FALDH deficiency in SLS keratinocytes causes the accumulation and diversion of fatty alcohol into alternative biosynthetic pathways. The striking lipid abnormalities in cultured SLS keratinocytes are distinct from those seen in fibroblasts and may be related to the stratum corneum dysfunction and ichthyosis in SLS.

Original languageEnglish (US)
Pages (from-to)410-419
Number of pages10
JournalJournal of Lipid Research
Volume49
Issue number2
DOIs
StatePublished - Feb 1 2008

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long-chain-aldehyde dehydrogenase
Fatty Alcohols
Keratinocytes
Metabolism
long-chain-alcohol dehydrogenase
Waxes
Diglycerides
Ichthyosis
Esters
Enzyme activity
Fibroblasts
Sjogren-Larsson Syndrome
Neurocutaneous Syndromes
Triglycerides
Fatty Acids
Biosynthetic Pathways
Enzymes
Lipids
Lipid Metabolism
Intellectual Disability

Keywords

  • Aldehyde dehydrogenase
  • Alkylglycerol
  • Epidermis
  • Ether glycerolipid
  • Fatty aldehyde
  • Ichthyosis
  • Mental retardation
  • Plasmalogen
  • Stratum corneum
  • Wax ester

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Abnormal fatty alcohol metabolism in cultured keratinocytes from patients with Sjögren-Larsson syndrome. / Rizzo, William B; Craft, Debra A.; Somer, Tara; Carney, Gael; Trafrova, Juliana; Simon, Marcia.

In: Journal of Lipid Research, Vol. 49, No. 2, 01.02.2008, p. 410-419.

Research output: Contribution to journalArticle

Rizzo, William B ; Craft, Debra A. ; Somer, Tara ; Carney, Gael ; Trafrova, Juliana ; Simon, Marcia. / Abnormal fatty alcohol metabolism in cultured keratinocytes from patients with Sjögren-Larsson syndrome. In: Journal of Lipid Research. 2008 ; Vol. 49, No. 2. pp. 410-419.
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AU - Simon, Marcia

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