Human Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics and Carbohydrate and Lipid Metabolism
Metabolism of Acylglycerols and Sphingolipids
Glycolipids

Glycosphingolipids

Glycosphingolipids are Glycolipids containing a ceramide moiety—composed of sphingosine and a fatty acid residue (Fig. 25.7)—along with one or more sugar residues. Many glycosphingolipids predominantly feature C₂₄ Fatty acids; for instance, Brain glycosphingolipids contain lignoceric, cerebronic, and nervonic acids. Lignoceric acid (C₂₃H₄₇COOH) is synthesized from acetyl-CoA. Cerebronic acid is the 2-hydroxy derivative of lignoceric acid, from which it is produced. Monounsaturated nervonic acid (C₂₃H₄₅COOH) is formed by the elongation of the oleic acid chain.

The simplest glycosphingolipids are galactosylceramide (GalCer) and glucosylceramide (GlcCer). GalCer is the major lipid of myelin, whereas GlcCer serves as the primary glycosphingolipid in Cell membranes of other Tissues and acts as a precursor to most complex glycosphingolipids.

The Biosynthesis of glycosphingolipids is catalyzed by an enzyme preparation derived from the brains of young rats (Fig. 25.8). UDP-galactose epimerase, utilizing uridine diphosphate glucose (UDPGlc) as a substrate, catalyzes the epimerization of the glucose moiety into galactose, yielding UDP-galactose (UDPGal). This reaction occurring in the brain is analogous to the corresponding reactions in The Liver and mammary gland (Fig. 21.3). Galactosylceramide is synthesized from ceramide and UDPGal. Sulfogalactosylceramide is formed through the reaction of galactosylceramide with 3'-phosphoadenosine-5'-phosphosulfate (PAPS, "active sulfate"). PAPS also participates in the biosynthesis of other sulfolipids, specifically sulfo(galacto)glycerolipids and sulfosteroids.

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Fig. 25.8. Biosynthesis of galactosylceramide and its sulfo derivative. PAPS: "active sulfate", phosphoadenosine-5'-phosphosulfate.

Gangliosides are synthesized from ceramide through the sequential addition of activated sugars—provided, for example, by UDPGlc and UDPGal—and a sialic acid, typically N-acetylneuraminic acid (Fig. 25.9). This pathway can generate a vast array of gangliosides with increasing molecular weights. Most Enzymes catalyzing The transfer of sugar residues from nucleotide sugars (Glycosyltransferases) are localized in the Golgi apparatus.

Functions of glycosphingolipids. As Components of the outer leaflet of The Plasma Membrane, glycosphingolipids are involved in cell-cell interactions and Cell Recognition. Some function as Antigens, such as the Forssman antigen and the ABO Blood group determinants. Similar oligosaccharide chains are also found in other plasma membrane Glycoproteins. Furthermore, several gangliosides act as receptors for Bacterial toxins (e.g., cholera toxin, which triggers the activation of adenylate cyclase).

Fig. 25.9. Biosynthesis of gangliosides. NeuAc — N-acetylneuraminic acid