Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Nov;88(5):1643–1648. doi: 10.1172/JCI115478

Sjögren-Larsson syndrome. Deficient activity of the fatty aldehyde dehydrogenase component of fatty alcohol:NAD+ oxidoreductase in cultured fibroblasts.

W B Rizzo 1, D A Craft 1
PMCID: PMC295691  PMID: 1939650

Abstract

Sjögren-Larsson syndrome (SLS) is an inherited disorder associated with impaired fatty alcohol oxidation due to deficient activity of fatty alcohol:NAD+ oxidoreductase (FAO). FAO is a complex enzyme which consists of two separate proteins that sequentially catalyze the oxidation of fatty alcohol to fatty aldehyde and fatty acid. To determine which enzymatic component of FAO was deficient in SLS, we assayed fatty aldehyde dehydrogenase (FALDH) and fatty alcohol dehydrogenase in cultured fibroblasts from seven unrelated SLS patients. All SLS cells were selectively deficient in the FALDH component of FAO, and had normal activity of fatty alcohol dehydrogenase. The extent of FALDH deficiency in SLS cells depended on the aliphatic aldehyde used as substrate, ranging from 62% of mean normal activity using propionaldehyde as substrate to 8% of mean normal activity with octadecanal. FALDH activity in obligate SLS heterozygotes was partially decreased to 49 +/- 7% of mean normal activity using octadecanal as substrate. Differential centrifugation studies in fibroblasts indicated that this FALDH enzyme was largely particulate; soluble FALDH activity was normal in SLS cells. Intact SLS fibroblasts oxidized octadecanol to fatty acid at less than 10% of the normal rate, but oxidized free octadecanal normally, suggesting that the FALDH affected in SLS is chiefly involved in the oxidation of fatty alcohol to fatty acid. These results show that the primary enzymatic defect in SLS is the FALDH component of the FAO complex, which leads to deficient oxidation of fatty aldehyde derived from fatty alcohol.

Full text

PDF
1643

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ferrell W. J., Yao K. C. Reductive and oxidative synthesis of saturated and unsaturated fatty aldehydes. J Lipid Res. 1972 Jan;13(1):23–26. [PubMed] [Google Scholar]
  2. Franks N. P., Lieb W. R. Partitioning of long-chain alcohols into lipid bilayers: implications for mechanisms of general anesthesia. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5116–5120. doi: 10.1073/pnas.83.14.5116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Harada S., Agarwal D. P., Goedde H. W. Electrophoretic and biochemical studies of human aldehyde dehydrogenase isozymes in various tissues. Life Sci. 1980 May 26;26(21):1773–1780. doi: 10.1016/0024-3205(80)90577-9. [DOI] [PubMed] [Google Scholar]
  4. Ichihara K., Kusunose E., Noda Y., Kusunose M. Some properties of the fatty alcohol oxidation system and reconstitution of microsomal oxidation activity in intestinal mucosa. Biochim Biophys Acta. 1986 Oct 3;878(3):412–418. doi: 10.1016/0005-2760(86)90250-x. [DOI] [PubMed] [Google Scholar]
  5. Ichihara K., Noda Y., Tanaka C., Kusunose M. Purification of aldehyde dehydrogenase reconstitutively active in fatty alcohol oxidation from rabbit intestinal microsomes. Biochim Biophys Acta. 1986 Oct 3;878(3):419–425. [PubMed] [Google Scholar]
  6. Jagell S., Gustavson K. H., Holmgren G. Sjögren-Larsson syndrome in Sweden. A clinical, genetic and epidemiological study. Clin Genet. 1981 Apr;19(4):233–256. doi: 10.1111/j.1399-0004.1981.tb00704.x. [DOI] [PubMed] [Google Scholar]
  7. Judge M. R., Lake B. D., Smith V. V., Besley G. T., Harper J. I. Depletion of alcohol (hexanol) dehydrogenase activity in the epidermis and jejunal mucosa in Sjögren-Larsson syndrome. J Invest Dermatol. 1990 Dec;95(6):632–634. doi: 10.1111/1523-1747.ep12514294. [DOI] [PubMed] [Google Scholar]
  8. Kitson T. M. The disulfiram--ethanol reaction: a review. J Stud Alcohol. 1977 Jan;38(1):96–113. doi: 10.15288/jsa.1977.38.96. [DOI] [PubMed] [Google Scholar]
  9. Miller K. W., Firestone L. L., Alifimoff J. K., Streicher P. Nonanesthetic alcohols dissolve in synaptic membranes without perturbing their lipids. Proc Natl Acad Sci U S A. 1989 Feb;86(3):1084–1087. doi: 10.1073/pnas.86.3.1084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mitchell D. Y., Petersen D. R. Oxidation of aldehydic products of lipid peroxidation by rat liver microsomal aldehyde dehydrogenase. Arch Biochem Biophys. 1989 Feb 15;269(1):11–17. doi: 10.1016/0003-9861(89)90081-7. [DOI] [PubMed] [Google Scholar]
  11. Nakayasu H., Mihara K., Sato R. Purification and properties of a membrane-bound aldehyde dehydrogenase from rat liver microsomes. Biochem Biophys Res Commun. 1978 Jul 28;83(2):697–703. doi: 10.1016/0006-291x(78)91045-8. [DOI] [PubMed] [Google Scholar]
  12. Rizzo W. B., Craft D. A., Dammann A. L., Phillips M. W. Fatty alcohol metabolism in cultured human fibroblasts. Evidence for a fatty alcohol cycle. J Biol Chem. 1987 Dec 25;262(36):17412–17419. [PubMed] [Google Scholar]
  13. Rizzo W. B., Dammann A. L., Craft D. A., Black S. H., Tilton A. H., Africk D., Chaves-Carballo E., Holmgren G., Jagell S. Sjögren-Larsson syndrome: inherited defect in the fatty alcohol cycle. J Pediatr. 1989 Aug;115(2):228–234. doi: 10.1016/s0022-3476(89)80070-8. [DOI] [PubMed] [Google Scholar]
  14. Rizzo W. B., Dammann A. L., Craft D. A. Sjögren-Larsson syndrome. Impaired fatty alcohol oxidation in cultured fibroblasts due to deficient fatty alcohol:nicotinamide adenine dinucleotide oxidoreductase activity. J Clin Invest. 1988 Mar;81(3):738–744. doi: 10.1172/JCI113379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. SJOGREN T., LARSSON T. Oligophrenia in combination with congenital ichthyosis and spastic disorders; a clinical and genetic study. Acta Psychiatr Neurol Scand Suppl. 1957;113:1–112. [PubMed] [Google Scholar]
  16. Theile U. Sjögren-Larsson syndrome. Oligophrenia--ichthyosis--di-tetraplegia. Humangenetik. 1974 May 17;22(2):91–118. [PubMed] [Google Scholar]
  17. Tuma D. J., Jennett R. B., Sorrell M. F. The interaction of acetaldehyde with tubulin. Ann N Y Acad Sci. 1987;492:277–286. doi: 10.1111/j.1749-6632.1987.tb48681.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES