Turnover of Docosahexaenoic Acid in Bis(Monoacylglycero)Phosphate Induced in Niemann-Pick Fibroblasts by Incubation in the Presence of Excess Fatty Acid

  • Srebrenka Huterer
  • John Wherrett
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 150)


The lysosomal phospholipid, bis(monoacylglycero)phosphate1 (BMP), accumulates selectively in both inherited2–4 and acquired5-6 disorders of lysosomal lipid catabolism. In those forms of Niemann-Pick disease with a profound deficiency of lysosomal sphingomyelinase, there is also an equally profound deficiency of phospholipase C7. Although sphingomyelin and phospholipids are substrates for the defective enzyme, there may be greater relative increase of BMP than of sphingomyelin and both sphingomyelin and BMP accumulate to a much greater degree than the other phospholipids. Lack of accumulation of phospholipids has been explained by the availability of other pathways excusive of phospholipase C for catabolism that are assumed to be unavailable to either sphingomyelin or BMP7.


Linoleic Acid Neutral Lipid Docosahexaenoic Acid Exogenous Fatty Acid Perhexiline Maleate 
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  1. 1.
    J. R. Wherrett and S. Huterer, Enrichment of bis(monoacylglyceryl)-phosphate in lysosomes from rat liver, J. Biol. Chem. 247:411 (1972).Google Scholar
  2. 2.
    G. Rouser, G. Kritchevsky, A. Yamamoto and G. Simon, Accumulation of glycerolphospholipid in classical Niemann-Pick disease, Lipids 3:287 (1968).PubMedCrossRefGoogle Scholar
  3. 3.
    J. R. Wherrett and N. B. Rewcastle, Adult neurovisceral lipidosis, Clin. Res. 17:665 (1969).Google Scholar
  4. 4.
    P. N. Seng, H. Debuch, B. Witter and H. R. Wiedemann, Bis(monoacylglycerin) phosphasaure-Vermehrung bei Sphingomyelinase (M. Niemann-Pick?) Hoppe-Seyler’s Z. Physiol. Chem. 352:280 (1971).CrossRefGoogle Scholar
  5. 5.
    S. Adachi, Y. Matsuzawa, T. Yokomura, K. Ishikawa S. Uhara, A. Yamamoto and M. Nishikawa, Changes in the lipid composition of rat liver and spleen following the administration of 4,4-dimethylaminoethoxyhexestrol, Lipids 7:1 (1972).PubMedCrossRefGoogle Scholar
  6. 6.
    H. Lullmann and R. Lullmann-Rauch and O. Wassermann, Drug-induced phospholipidosis, Crit. Rev. Toxicol. 4:185 (1975).Google Scholar
  7. 7.
    S. Huterer, J. R. Wherrett, A. Poulos and J. W. Callahan, Deficiency of phospholipase C acting on phosphatidylglycerol in Niemann-Pick disease, Neurology (NY) 33:67 (1983).Google Scholar
  8. 8.
    S. Huterer and J. R. Wherrett, Metabolism of bis(monoacylglycero)-phosphate in macrophages, J. Lipid Res. 20:966 (1979).PubMedGoogle Scholar
  9. 9.
    S. Huterer and J. R. Wherrett, Incorporation of polyunsaturatd fatty acids in bis(monoacylglycero)phosphate and other lipids of macrophage! and of fibroblasts from control and Niemann-Pick patients, Biochim. Biophys. Acta 876:318 (1985).Google Scholar
  10. 10.
    P-Y. Tsai and R. P. Geyer, Effect of exogenous fatty acids on the retention of phospholipid acyl groups by mouse L fibroblasts, Biochim Biophys. Acta 528:344 (1978).PubMedGoogle Scholar
  11. 11.
    A. A. Spector, S. N. Mathur, T. L. Kaduce and B. T. Hyman, Lipid nutrition and metabolism of cultured mammalian cells, Prog. Lipid Res 19:155 (1981).CrossRefGoogle Scholar
  12. 12.
    R. J. Mason, T. P. Stossei and M. Vaughan, Lipids of alveolar macrophages, polymorphonuclear leukocytes, and their phagocytic vesicles, J. Clin. Invest. 51:2399 (1972).PubMedCrossRefGoogle Scholar
  13. 13.
    J. Brotherus, O. Renkonen, J. Herrmann and W. Fischer, Novel stereoconfiguration in lyso-bis-phosphatidic acid of cultured BHK-cells, Chem. Phys. Lipids 13:178 (1974).PubMedCrossRefGoogle Scholar
  14. 14.
    F. R. Cochran, V. L. Roddick, J. R. Connor, J. R. Thornburg and M. Waite, Regulation of arachidonic acid metabolism in resident and BCG-activated alveolar macrophages: role of lyso(bis)phosphatidic acid, J. Immunol. 138:1877 (1987).PubMedGoogle Scholar
  15. 15.
    J. Brotherus, T. Niinioja, K. Sandelin and O. Renkonen, Experimentall caused proliferation of lysosomes in cultured BHK cells involving an increase of biphosphatidic acids and triglycerides, J. Lipid Res. 18: 379 (1977).PubMedGoogle Scholar
  16. 16.
    S. Albouz, J-M. Boutry, G. Dubois, R. Bourdon, J-J. Hauw and N. Baumann, Lipid and lysosomal exzymes in human fibroblasts cultured with perhexiline maleate, Naunyn-Schmiedeberg’s Arch. Pharmacol. 317:173 (1981).CrossRefGoogle Scholar
  17. 17.
    G. Albert-Tulkens, F. Van Hoof and P. Tulkens, Gentamicin-induced lysosomal phospholipidosis in cultured rat fibroblasts, Lab. Invest. 40:481 (1979).Google Scholar
  18. 18.
    H. S. Kruth, M. E. Comly, J. D. Butler, M. T. Vanier, J. K. Fink, D. A. Wenger, S. Patel and P. G. Pentchew, Type C Niemann-Pick disease: abnormal metabolism of low density lipoprotein in homozygous and heterozygous fibroblasts, J. Biol. Chem. 261:16769 (1986).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Srebrenka Huterer
    • 1
  • John Wherrett
    • 1
  1. 1.Department of Medicine (Neurology)University of TorontoTorontoCanada

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