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Experimental Brain Research

, Volume 5, Issue 4, pp 267–273 | Cite as

Acetyl transport mechanisms. Involvement of N-Acetyl aspartic acid in de novo fatty acid biosynthesis in the developing rat brain

  • A. F. D'AdamoJr.
  • L. I. Gidez
  • F. M. Yatsu
Article

Summary

The incorporation into fatty acids of N-acetyl aspartic acid, labeled in the acetyl group, was investigated during brain growth and development. Parasagittal injection of the acetyl amino acid into rats of various ages resulted in maximum incorporation just before and during myelination, a period in which the endogenous N-acetyl aspartic acid increases rapidly. The results indicate that the only barrier to the uptake of this compound is at the blood-brain barrier. Gas liquid chromatographic analysis of the fatty acid methyl esters isolated by mild base hydrolysis showed that the labeled fatty acids were primarily the C16 and C18 long-chain acids. These results indicate that N-acetyl aspartic acid is actively involved in de novo fatty acid synthesis throughout growth and development of the brain. It is suggested that, in the brain, N-acetyl aspartic acid is a constituent of the acetyl transport system for extra-mitochondrial fatty acid synthesis.

Key Words

De novo fatty acid synthesis Acetyl transport mechanisms N-acetyl aspartic acid Brain development 

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References

  1. Bennett, M., and E. Coon: Inexpensive cartridge for the collection of radioaktive methyl esters from gas-liquid chromatographs. J. Lipid Res. 7, 448–449 (1966).Google Scholar
  2. Benuck, M., and A.F. D'Adamo, Jr.: Studies on the metabolism of N-acetyl-L-aspartic acid in the peripheral tissues of the rat. Abs. Inter. Soc. Neurochem. (Strasbourg) 1, 19 (1967).Google Scholar
  3. Berl, S., A. Lajtha and H. Waelsch: Amino acid and protein metabolism. VI. Cerebral compartments of glutamic acid metabolism. J. Neurochem. 7, 186–197 (1961).Google Scholar
  4. Berlinguet, L., and M. Laliberté: Metabolism of N-acetyl-L-aspartic acid in mice. Canad. J. Biochem. 44, 783–789 (1966).Google Scholar
  5. D'Adamo, A.F., Jr., and D. Haft: An alternate pathway of glutamic acid catabolism in the perfused liver. Fed. Proc. 21, 6 (1962).Google Scholar
  6. —: An alternate pathway of α-ketoglutarate catabolism in the isolated, perfused liver. J. biol. Chem. 240, 613–617 (1965).Google Scholar
  7. —, and F.M. Yatsu: Acetate metabolism in the nervous system. N-acetyl-L-aspartic acid and the biosynthesis of brain lipids. J. Neurochem. 13, 961–965 (1966).Google Scholar
  8. Fritz, I.B., and K.T.N. Yue: Effects of carnitine on acetyl CoA oxidation by heart muscle mitochondria. Amer. J. Physiol. 206, 531–535 (1964).Google Scholar
  9. Gebhard, O., and H. Veldstra: N-acetyl aspartic acid. Experiments on the biosynthesis and function. J. Neurochem. 11, 613–617 (1964).Google Scholar
  10. Gidez, L.I., P.S. Roheim and H.A. Eder: Effect of diet on the cholesterol ester composition of liver and of plasma lipoproteins in the rat. J. Lipid Res. 6, 377–382 (1965).Google Scholar
  11. Goldstein, F.B.: Biosynthesis of N-acetyl-L-aspartic acid. Biochim. biophys. Acta (Amst.) 33, 583–584 (1959).Google Scholar
  12. Knizley, H., Jr: The enzymatic synthesis of N-acetyl-L-aspartic acid by a water-insoluble preparation of a cat brain acetone powder. J. biol. Chem. 242, 4619–4622 (1967).Google Scholar
  13. Klee, C.B., and L. Sokoloff: Mitochondrial differences in mature and immature brain. J. Neurochem. 11, 709–716 (1964).Google Scholar
  14. —: Amino acid incorporation into proteolipid of myelin in vitro. Proc. nat. Acad. Sci. (Wash.) 53, 1014–1021 (1965).Google Scholar
  15. Margolis, R.V., S.S. Barkulis and A. Geiger: A comparison between the incorporation of 14C from glucose into N-acetyl-L-aspartic acid and aspartic acid in brain perfusion experiments. J. Neurochem. 5, 379–384 (1960).Google Scholar
  16. Masoro, E.J.: Biochemical mechanism related to the homeostatic regulation of lipogenesis in animals. J. Lipid Res. 3, 149–164 (1962).Google Scholar
  17. McIntosh, J.C., and J.R. Cooper: Function of N-acetyl aspartic acid in the brain: effects of certain drugs. Nature (Lond.) 203, 658 (1964).Google Scholar
  18. Morrison, W.R., and L.M. Smith: Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride-methanol. J. Lipid Res. 5, 600–608 (1964).Google Scholar
  19. Mussini, E., F. Marcucci and S. Garattini: Postnatal change in brain N-acetyl-L-aspartic acid content of normal and hypothyroid suckling rats. J. Neurochem. 14, 551–554 (1967).Google Scholar
  20. Okita, G.T., J.J. Kabara, F. Richardson and G.V. LeRoy: Assaying compounds containing tritium and 14C. Nucleonics 15, 111–114 (1957).Google Scholar
  21. Smith, M.E.: The effect of fasting on lipid metabolism of the central nervou system of the rat. J. Neurochem. 10, 531–536 (1963).Google Scholar
  22. —, and L.F. Eng: The turnover of the lipid components of myelin. J. Am. Oil Chemists, Soc. 42, 1013–1018 (1965).Google Scholar
  23. Spencer, A.F., and J.M. Lowenstein: The supply of precursors for the synthesis of fatty acids. J. biol. Chem. 237, 3640–3648 (1962).Google Scholar
  24. Srere, P.A., and A. Bhaduri: Incorporation of radioactive citrate into fatty acids. Biochim. biophys. Acta (Amst.) 59, 487–489 (1962).Google Scholar
  25. Tallan, H.H.: Studies on the distribution of N-acetyl-L-aspartic acid in brain. J. biol. Chem. 224, 41–45 (1957).Google Scholar
  26. Waelsch, H.: Amino acid and protein metabolism. In: Neurochemistry, pp. 289–320. Ed. by K.A.C. Elliott, I.H. Page and J.H. Quastel. Springfield, Ill.: C.C. Thomas 1962.Google Scholar

Copyright information

© Springer-Verlag 1968

Authors and Affiliations

  • A. F. D'AdamoJr.
    • 1
  • L. I. Gidez
    • 1
  • F. M. Yatsu
    • 1
  1. 1.Saul R. Korey Department of Neurology and the Departments of Biochemistry and MedicineAlbert Einstein College of Medicine, Yeshiva UniversityNew YorkUSA

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