Characterization of some minor gangliosides in Tay-Sachs brains

Robert K. Yu, Toshihiro Itoh, Herbert C. Yohe, Lawrence J. Macala

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The ganglioside distribution of Tay-Sachs brain was re-examined in detail. In both the gray and white matter, the levels of lipid-bound sialic acid were increased 6- and 10-fold, respectively, over normal infant brain, and approximately 90% of the total ganglioside was GM2. The level of GM2 was increased about 90 times in gray matter and 220 times in white matter in comparison with that in normal controls. The level of GD1a-GaINAc was increased 19 times and 10 times in gray and white matter, respectively. The concentration of GD2 was increased about 4-fold in Tay-S-Sachs white matter. In addition, the GM3 level was increased 2.7 and 3.5 times and the GD3 level 2 and 2.4 times over normal gray and white matter, respectively. However, the levels of other complex gangliosides such as GM1, GD1a, GD1b, GT1b and GQ1b decreased remarkably. Since GM2, GD2, GD1a-GalNAc and a recently characterized ganglioside GM1b-GalNAc possess a common N-acetylgalactosaminyl terminal structure, their accumulation in Tay-Sachs brains is therefore consistent with the known hexosaminidase A deficiency. However, the accumulation of hexosamine-free GM3 and GD3 is not. The in vitro incorporation of N-acetylgalactosamine into GM3 to form GM2 was examined in a rat brain microsomal fraction in the presence of large amounts of other glycolipids. Acidic glycolipids were slightly stimulating and then became increasingly inhibitory when the molar ratio of lipid to substrate GM3 exceeded 10 to 1. Neutral glycolipids and the phospholipid, phosphatidylcholine, were inhibitory at all levels tested. The data suggest that the accumulation of GM3 and GD3 in Tay-Sachs brains could be due to an inhibition of N-acetylgalactosaminyl-transferas by high levels of glycolipids, and the inhibition is not due to chelation of the obligate divalent cation necessary for the activity of this enzyme. The inhibition of this enzyme may also be responsible for the decreased levels of other complex gangliosides.

Original languageEnglish (US)
Pages (from-to)47-52
Number of pages6
JournalBrain Research
Volume275
Issue number1
DOIs
Publication statusPublished - Sep 19 1983
Externally publishedYes

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Keywords

  • Tay-Sachs disease
  • gangliosides
  • gangliosidosis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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