The Distribution of Lipids in the Human Nervous System‐v. Gangliosides and Allied Neutral Glycolipids of Infant Brain

Abstract

Gangliosides and allied neutral glycosylceramides were isolated from human infant (2-24 months of age) cerebral cortex and white matter. The individual glycolipids were separated quantitatively by a combination of column and thin-layer chromatographic methods on silica gel, DEAE-cellulose and Sephadex G-25. In cerebral cortex G D 1 , and GM1 were the major fractions and constituted more than 70 per cent of the total gangliosides. The concentrations of neutral glycolipids, except for galactosylceramides, were very low: lactosylceramide and glucosylceramide comprised 30 and 5 nmol/g wet weight, respectively. In white matter their concentrations were 10 times higher. The ganglioside concentration was only 50 per cent of that in cerebral cortex: the difference was accounted for mainly by the much lower content of the major di-and trisialogangliosides.Stearic acid was the predominant fatty acid of all brain gangliosides. GM3 and G D 3 had a considerable content of the very long-chain fatty acids, Czz-C24, particularly in the white matter. Glucosylceramide and lactosylceramide had almost identical fatty acid patterns between each other in cerebral cortex and white matter. In the cerebral cortex stearic acid and in the white matter the very long-chain acids predominated. d20: 1 Sphingosine comprised more than 20 per cent of total sphingosine in all the gangliosides of the G1-and Gz-series. GM3 and GD3 like lactosylceramide contained significantly less of d20: 1 sphingosine. The findings suggest the existence of separate compartments for the biosynthesis of the gangliosides. Glucosylceramides and lactosylceramides of white matter have the same ceramide composition as the galactosylceramides with normal fatty acids and are thus unlikely to be intermediates in the metabolism of the major brain gangliosides which have a completely different fatty acid composition.A DETAILED determination of the ganglioside composition has only been performed on single human infant brains (SVENNERHOLM, 1963, 1967SUZUKI, 1965). In our recent study of a large number of foetal and infant brains (VANIER et al., 1971) only the four major gangliosides were determined and no data on other gangliosides were included. More detailed knowledge of the concentrations and compositions of the minor gangliosides and allied glycolipids is essential for a better understanding of the ganglioside metabolism in various types of cells and subcellular particles (HOLM et . KLENK (1942) originally identified stearic acid as the major fatty acid of brain gangliosides. TRAMS et al. (1962) reported the occurrence of minor amounts of 20:O and 22:O besides the predominating 18:O fatty acid, In many subsequent investigations stearic acid has been shown to be the predominating fatty acid of the total brain gangliosides fraction, but no systematic study is available on the fatty acid composition of the individual gangliosides in human brain. CISand C,,-sphingosines constituted approx. 90 per cent of the sphingosines of total human Present address: Fondation Gillet, Hapita...

Differences in sphingosine and fatty acid patterns of the major gangliosides of bovine retina

“…Differences in fatty acid patterns of individual gangliosides from nervous tissues are reported with an increasing frequency [2][3][4][5][6][7]. According to Holm et al [2] and Vanier et al [3] the reported differences might be explained by a possible existence of separate sites for the biosynthesis of the individual gangliosides.…”

“…According to Holm et al [2] and Vanier et al [3] the reported differences might be explained by a possible existence of separate sites for the biosynthesis of the individual gangliosides. This explanation was further supported by the analysis of the sphingosine patterns of the different cerebral gangliosides [3]. Thus those gangliosides which had different fatty acid patterns also differed in the sphingosine patterns.…”

“…The GD3 was isolated in one batch and the GDIa, GD1 b and GT1 together in another batch. The fatty acid and sphingosine patterns of the two samples were analysed by GLC according to Vanier et al [3].…”

Interaction of cholera toxin and membrane GM1 ganglioside of small intestine.

“…Although the total ganglioside content of the mucosa differed manyfold between the species, the concentration of ganglioside GM1 differed much more. Pig had a concentration that was approximately 20 times larger than that in man, and beef a concentration 21 times larger than that in pig, which means that the GM1 concentration of human intestinal mucosa was only 1/400 of that in the bovine mucosa. Human and porcine mucosa contained large concentrations of simple ganglioside mono-and disialosyllactosylceramide (GM3 and GDM).…”

“…Porcine mucosa (555 g), porcine muscular layer (2.0 kg), bovine mucosa (185 g), bovine muscular layer (650 g), human mucosa (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) GM3, were isolated by partition and purified by column chromatography on Sephadex G-25 and Silica Gel G (Svennerholm, in preparation). All the ganglioside preparations, particularly those of human and pig mucosa, were still very impure, and the gangliosides of all the six sources were further purified by mild alkaline hydrolysis, chromatography on Sephadex G-25, DEAE-Sephadex A-25 (20), Sephadex G-25, and finally on Silica Gel H (21). The quantitative determinations of gangliosides were performed on the final eluate of the Silica Gel H column by the resorcinol method (22).…”