Ganglioside biochemistry

Abstract

Gangliosides are sialic acid-containing glycosphingolipids. They occur especially on the cellular surfaces of neuronal cells, where they form a complex pattern, but are also found in many other cell types. The paper provides a general overview on their structures, occurrence, and metabolism. Key functional, biochemical, and pathobiochemical aspects are summarized.

Figure 1

Sialic acids.

Figure 2

Structure of GQ1b, one of the most abundant gangliosides in adult human brain, which is involved in long term potentiation, synaptic plasticity, and improvement of cognitive function [23].

Figure 3

GD1aGalNAc and GM4.

Figure 4

Formation of SSEA-4 from globotriaosylceramide (Gb3Cer). SSEA, stage-specific embryonic antigen; T, transferase; FUT, fucosyltransferase (modified from [24]).

Figure 5

Examples for gangliosides from echinoderms: LG-2 from the starfish Astropecten latespinosus [47] and LLG-5 from the starfish Linckia laevigata [–50].

Figure 6

Representative structures of sphingoid bases, in this case (d18:1), (d18:0), and (t18:0).

Figure 7

Representative structures of gangliosides that are abundant in adult human brain.

Figure 8

Example of a ganglioside lactone.

Figure 9

Ceramide biosynthesis, shown for a ceramide with C₁₈ sphingosine. R = alkyl; chain length depend on the availability of the corresponding acyl CoAs and the identity of the ceramide synthase.

Figure 10

Reaction of β1,3-N-acetyl-glucosaminyltransferase (β3GlcNAcT) and examples of downstream gangliosides of the neolacto series.

Figure 11

Structures of hematosides.

Figure 12

Ganglioside biosynthesis (modified from [141]).

Figure 13

Structure of a c-series ganglioside.

Figure 14

Bis(monoacylglycero)phosphate with two oleic acid moieties.

Figure 15

Lysosomal membrane pools.

Figure 16

Lysosomal ganglioside degradation pathway (modified from [233]). Names of inherited diseases (in boxes), enzymes, and lipid-transfer proteins required in vivo are given.

Figure 17

Synthetic substrates for the determination of β-hexosaminidase A (R = SO₃ ⁻) and β-hexosaminidases A + B (R = H).

Figure 18

LysoGM2 (n = 12, 14).

Figure 19

Structure of Liga20, a semitruncated and halogenated GM1 analog that can pass the blood-brain barrier.

Figure 20

Schematic ganglioside uptake by cultured cells (modified from [306]).

Figure 21

Example of a GM1 analog [307] spin labelled with a 4,4-dimethyl-oxazolidine-1-oxyl- (DOXYL-) residue and a fluorescent GM1 analog used for STED microscopy [308].