Submitted on October 17, 2007
Accepted on October 29, 2007
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, and Marcia Simon
Pediatrics, Univeersity of Nebraska Medical Center, Omaha, NE 68198-5456
Corresponding Author: wrizzo{at}unmc.edu
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 less than 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 accumulation and diversion of fatty alcohol into alternate biosynthetic pathways. The striking lipid abnormalities in cultured SLS keratinocytes are distinct from those seen in fibroblasts and may be responsible for the stratum corneum dysfunction and ichthyosis in SLS.
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