Different Types of Sphingolipids and Their Biosynthesis

(Last Updated On: July 21, 2021)
structure of sphingolipids
The structure of the sphingolipids. Image: Karol Langner via Common Wikimedia

Classification of the lipids

Lipids are classified into two classes; saponifiable lipids and non-saponifiable lipids. In a saponifiable lipid family, there are two types of lipids Glycerol Esters and Non-glycerol Esters. Glycerol esters include triacylglycerols and phosphoglycerols while non-glycerol esters include two classes of lipids; waxes and sphingolipids. Both lipids are saponifiable because they contain fatty acid residues. Upon base promoted hydrolysis (saponification) they yield free fatty acid salts.

However, non-saponifiable lipid family includes steroids, eicosanoids, terpenes, pheromones, and fat-soluble vitamins and they don’t have any fatty acid residues that can be released during the base promoted hydrolysis. Therefore, they are called as non-saponifiable lipids.

Sphingolipids are found in the cell membranes and constitute the second most abundant membrane lipids while the first most abundant membrane lipids are phospholipids. Sphingolipids are further classified into two subclasses.

  1. Sphingophospholipids; sphingolipids that contain a phosphate attached to the ceramide unite to provide an attachment site for the polar groups
  2. Glycolipids; the sphingolipids that contain an oligosaccharide moiety attached to the ceramide unit.

Sphingolipids are so-called because they contain sphingosine, a long chain aliphatic amino alcohol, long-chain fatty acid, and phosphate group or oligosaccharide moiety attached to the polar head group. The fatty acid residue is attached to the sphingosine through an amide linkage to form ceramide. The fatty acyl part of the ceramide can be released as fatty acid salt during saponification.

Biosynthesis of sphingosine
Biosynthesis of the sphingosine moiety of the sphingolipids

Biosynthesis of sphingolipids

Sphingolipids are synthesized in the lumen of Endoplasmic Reticulum. Like phospholipids, sphingolipids also contain two non-polar tails (sphingosine and fatty acid) and one polar head group (polar group attached to the phosphate moiety).

Biosynthesis of sphingolipids starts from the condensation of serine residue with a palmitoyl-CoA. Serine reacts with the palmitoyl-CoA catalyzed by the enzyme 3-ketosphinganine (dehydrosphinganin) synthase to form dehydrosphinganine. Dehydrosphinganin synthase required pyridoxal phosphate as a cofactor which is a biologically active form of vitamin B6 or pyridoxine.

Dehydrosphinganine is then reduced to the dehydrosphingosine catalyzed by the NAPDH-dependent enzyme dehydrosphingosine reductase. Then FAD-dependent enzyme dehydrogenase catalyzes the conversion of dehydrosphingosine to sphingosine. Sphingosine is condensed with fatty acyl-CoA to form ceramide catalyzed by the enzyme sphingosine acyltransferase.

Ceramide is the branch point of synthesis of two classes of sphingolipids. One branch leads to the synthesis of glycolipids and the other branch leads to the formation of sphingophospholipids.

  1. When CDP-choline reacts with ceramide catalyzed by ceramide choline phosphotransferase then sphingomyelin is produced. Sphingomyelin is a type of sphingophospholipid found mostly in the myelin sheath of nerve cells.
  2. However, condensation of UDP-sugar (galactose or glucose) with ceramide gives gangliosides.

Thus, sphingophospholipids and glycolipids both share a common biosynthetic pathway. However, synthesis and degradation of sphingolipids must be maintained because any defect in the enzymes involved in the sphingolipid catabolic pathway may lead to a medical condition called sphingolipidosis or lysosomal disease or lipid storage disease.

There are many types of ganglioside that can be synthesized by the consecutive addition of sugar residues on ceramide. For example, condensation of UDP-glucose with ceramide produces glucosylceramide (glucocerebroside).

Glucocerebroside condenses with a molecule of UDP-Galactose to form lactocerebroside (or lactosylceramide) and further condensation with CMP –NeuNAc (CMP-activated N-acetyl neuraminic acid) leads to the formation of GM3.

Depending upon the types of sugar added and branch patterns, different types of gangliosides can be synthesized from lactosylceramide. All the gangliosides are synthesized from glucocerebrosides and, therefore, synthesis of glucocerebroside is a rate-limiting and committed step of ganglioside biosynthesis.

There are two types of glycolipids; cerebrosides and gangliosides. Glycolipids with single sugar units are called cerebrosides while glycolipids with oligosaccharide units are called gangliosides. Glycolipids also play a role in membrane fluidity maintenance and gangliosides are the most important glycolipids for the neuronal membrane, especially in synapses.

Gangliosides are of different types; GM1, GM2, GM3, and many more types, while cerebrosides are of two types glucocerebrosides and galactocerebrosides. They all have their own roles in the cell membrane and maintain the fluidity of the membrane.

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