Recent Advances in Structural Analysis of Gangliosides: Primary and Secondary Structures

Rk, Yu; Ta, Koerner; Pc, Demou; Jn, Scarsdale; Jh, Prestegard

doi:10.1007/978-1-4684-1200-0_8

Cited by 14 publications

(2 citation statements)

References 35 publications

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“…Gangliosides are concentrated in synaptic membranes and are important for neurotransmission at the synapse. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Since membranes are supported by the hydrogenbonded water matrix, Yu et al 27 suggested that primary and secondary structure of gangliosides in aqueous environment is a crucial influence on interactions of molecules at the membrane surface. In gangliosides, possible hydrogen bonding sites are the negatively charged carboxyl groups (COO-) of sialic acid moieties and the hydroxyl (OH), -0-, -NHCOCH3 groups of the other sugars.…”

Section: Ganglioside Binding Sites For Water and Alcoholmentioning

confidence: 99%

FTIR Evidence for Alcohol Binding and Dehydration in Phospholipid and Ganglioside Micelles

Yurttas

Dale

Klemm

1992

Alcoholism Clin & Exp Res

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We theorize that intoxicants and modern anesthetics bind at the membrane-water interface and displace (dehydrate) bound water molecules by breaking the hydrogen bonds. We tested this hypothesis by examining the effect of butanol on the binding of water to the polar regions of lipids in reversed micelles. Understanding the mechanisms of intoxication requires studies in physiologically relevant systems such as systems containing sialoglycoconjugates, especially gangliosides, which concentrate in the synapses of neural tissue. Therefore, we compared butanol effects on phospholipid with effects on ganglioside. Hydrogen-bond breaking activity of 1-butanol was studied in reversed micelles made of dipalmitoylphosphotidylcholine (DPPC), ganglioside (GM1 and GT1b) or the lipid mixture in a D2O-CCl4 medium. Fourier transform infrared spectroscopy (FTIR) data indicated that 1-butanol binds to DPPC and to gangliosides. Adding GM1 to the DPPC micelles introduces a new binding site for the alcohol. GT1b binds more butanol than GM1, because of more binding sites provided by extra sialic acid moieties. Spectral red shifts indicate that both water and butanol bind to the C = O group of sialic acid. Butanol partially releases the surface-bound water by disrupting hydrogen bonds, as indicated by an appearance of a sharp new free OD stretching band of the released D2O molecules. However, control studies with lipid-free systems in CCl4 revealed that a free OD peak could occur from a deuterium exchange reaction between D2O and 1-butanol(ol-h).(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Ganglioside Binding Sites For Water and Alcoholmentioning

confidence: 99%

FTIR Evidence for Alcohol Binding and Dehydration in Phospholipid and Ganglioside Micelles

Yurttas

Dale

Klemm

1992

Alcoholism Clin & Exp Res

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“…Gangliosides are found in nearly all vertebrate tissues but are most heavily concentrated in the CNS. Although much is known about ganglioside structures (Ledeen, 1983;Yu et al, 1984), less is known about ganglioside functions or about the genes that regulate ganglioside biosynthesis. Because gangliosides are enriched in neuronal membranes and may function during brain development in cell growth, adhesion, and differentiation (Fishman and Brady, 1976; Ledeen, 1983), it is possible that inherited mutations in ganglioside synthesis may cause abnormalities in neural development that could lead to embryonic lethality.…”

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confidence: 99%

Ganglioside Composition of Normal and Mutant Mouse Embryos

Bouvier

Seyfried

1989

Journal of Neurochemistry

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The enrichment of gangliosides in neuronal membranes suggests that they play an important role in CNS development. We recently found a marked tetrasialoganglioside deficiency in twl/twl mutant mouse embryos at embryonic day (E)-11. The recessive twl/twl mutants die at embryonic ages E-9 to E-18 from failed neural differentiation in the ventral portion of the neural tube. In the present study, we examined the composition and distribution of gangliosides in twl/twl mutant mouse embryos at E-12. The total ganglioside sialic acid concentration was significantly lower in the mutants than in normal (+/-) embryos. The mutants also expressed significant deficiencies of gangliosides in the "b" metabolic pathway (GD3, GD1b, GT1b, and GQ1b) and elevations in levels of gangliosides in the "a" metabolic pathway (GM3, GM2, GM1, and GD1a). These findings suggest that the mutants have a partial deficiency in the activity of a specific sialyltransferase in the b pathway. Regional ganglioside distribution was also studied in E-12 normal mouse embryos. The ganglioside composition in heads and bodies was similar to each other and to whole embryos. Total ganglioside concentration and the distribution of b pathway gangliosides were significantly higher in neural tube regions than in nonneural tube regions. These findings suggest that b pathway gangliosides accumulate in differentiating neural cells and that the deficiency of these gangliosides in the twl/twl mutants is closely associated with failed neural differentiation.

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Effect of purkinje cell loss on cerebellar gangliosides in nervous mutant mice

Seyfried

Bernard

1987

J of Neuroscience Research

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The distribution of cerebellar gangliosides was studied in adult (73 +/- 2 days) nervous (nr/nr) mutant mice which lose 50-90% of their Purkinje cells. This neuronal loss is associated with significant reductions in cerebellar weight and ganglioside concentration. The cerebellar dry weights (mg) and the ganglioside concentrations (microgram N-acetylneuraminic acid per 100 mg dry weight) in nr/nr mice and age-matched normal littermates (+/?) are 7.4 +/- 0.3 mg and 13.2 +/- 0.4 mg; and 411.7 +/- 4.8 micrograms and 438.5 +/- 2.1 micrograms, respectively. Abnormalities were also observed for the concentration of certain ganglioside species. Most notably, GT1a is significantly reduced by 42%, and GD3 is significantly increased by 29% in the nr/nr mice compared to the +/? mice. The nr/nr mice also express a slight but significant reduction in GT1b. No ganglioside abnormalities were observed between the nr/nr and +/? mice in cerebral cortex. We previously found reduced cerebellar GT1a content in other mutants that also lose Purkinje cells, i.e., sg/sg, pcd/pcd, and Lc/+. GT1a is not reduced, however, in wv/wv mice that lose mostly granule cells. The findings in nr/nr mice are therefore consistent with our hypothesis that GT1a is enriched in Purkinje cells. GD1a, which is enriched in mature granule cells, is not reduced in the nr/nr mice.(ABSTRACT TRUNCATED AT 250 WORDS)

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Recent Advances in Structural Analysis of Gangliosides: Primary and Secondary Structures

Cited by 14 publications

References 35 publications

FTIR Evidence for Alcohol Binding and Dehydration in Phospholipid and Ganglioside Micelles

FTIR Evidence for Alcohol Binding and Dehydration in Phospholipid and Ganglioside Micelles

Ganglioside Composition of Normal and Mutant Mouse Embryos

Effect of purkinje cell loss on cerebellar gangliosides in nervous mutant mice

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