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GANGLIOSIDE 1− COMPOSITION OF BRAIN IN TAY‐SACHS DISEASE: INCREASED AMOUNTS OF GD2 AND N‐ACETYL‐β‐D‐GALACTOSAMINYL GD1a GANGLIOSIDE
Author(s) -
Iwamori M.,
Nagai Y.
Publication year - 1979
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1979.tb04560.x
Subject(s) - ganglioside , tay sachs disease , chemistry , ceramide , biochemistry , residue (chemistry) , chromatography , carbohydrate , myelin , medicine , central nervous system , endocrinology , biology , apoptosis , disease
— The ganglioside composition of the brain of a patient with Tay‐Sachs disease (TS‐brain) was determined by a newly developed ganglioside‐mapping procedure and compared with that of an age‐matched control brain. GM2 ganglioside was the predominant component in TS‐brain and the following gangliosides were also found, GM1, GD1a, GD1b and GT1 (major gangliosides in normal brain), and GM3, GD3, GD2 and GD1a‐GAN (minor or undetectable components of normal brain). Individual gangliosides were isolated by column chromatography using a combination of DEAE‐Sepharose, Iatrobeads and Silica Gel 60 and their structures were confirmed by comparing them with authentic standards using TLC, analysing their carbohydrate compositions by gas‐liquid chromatography and cleaving them sequentially with glycosidases. The amounts of individual components were measured by quantitative densitometric scanning of the thin‐layer plates. As a reflection of myelin breakdown, no sialosylgalactosyl ceramide was detectable in TS‐brain. Although the total amounts of all gangliosides except GM2 in TS‐brain were low, there were normal molar ratios of the main gangliosides in normal brain, that is, GM1, GD1a, GD1b and GT1. In comparison with the amount of GDla ganglioside, the amounts of GM2, GD2 and GD1a‐GAN, which contain N ‐acetylgalactosamine as a terminal carbohydrate residue, were all elevated in TS‐brain. The long chain bases of individual gangliosides contained both C‐18 and C‐20 sphingosine in different ratios and the ratio of C‐20 to C‐18 increased in the gangliosides in the order: GM2 < GM1 < GD1a < GD1a‐GAN < GD1b < GT1 in both normal brain and TS‐brain. In contrast, GD2 and GD3 gangliosides consisted mainly of C‐18 sphingosine. The C‐20 to C‐18 ratios of individual gangliosides in the TS‐brain were lower than those of age‐matched control brain. Hexosaminidase from Turbo cornutus showed the same specific activity and K m value in catalysing the cleavage of terminal N ‐acetylgalactosaminyl residues from GM2, GD2 and GD1a‐GAN, suggesting that the brain gangliosides that increase in Tay‐Sachs disease may be cleaved by the same enzyme.