Blood & Laboratory Values

Sphingolipids – Function & Diseases

sphingolipids

Alongside glycerophospholipids and cholesterol , sphingolipids are among the building blocks of the cell membrane. Chemically, they are derived from sphingosine, an unsaturated amino alcohol with 18 carbon atoms. Mainly nervous system and brain are rich in sphingolipids.

What are sphingolipids?

All cell membranes contain glycerophospholipids, cholesterol and sphingolipids. Sphingolipids consist of the basic structure sphingosine, on whose amino group a fatty acid is esterified. Sphingosine is an amino alcohol containing a chain of 18 carbon atoms. The sphingolipids can be divided into three groups.

These are the ceramides, the sphingomyelins and the glycosphingolipids. Ceramides represent the simplest sphingolipids. Here sphingosine is esterified with a fatty acid. An amphiphilic double structure with double lipid layers forms. The amphiphilicity is created by the two hydrocarbon tails pointing in opposite directions. Sphingomyelins are esterified at the hydroxyl group of the sphingosine backbone with a phosphoric acid, which in turn is esterified with either an alcohol or choline .

Finally, glycosphingolipids have a glycosidic bond with a sugar residue on the hydroxyl group of the sphingosine backbone. The cerebrosides are monohexoses, while the gangliosides are glycosidically bound to an oligosaccharose.

Function, effect & tasks

The sphingolipids fulfill different functions. Their structure plays a major role in this. The sphingolipids with the simplest structure, the ceramides, are particularly involved in the structure of the horny layer of the skin . Due to their amphiphilic nature, they can form a lipid double layer that protects the skin from drying out. 

In addition to this function, ceramides also fulfill numerous other tasks. These include signal transmission or tasks in controlling cell division. In addition to glycerophospholipids and cholesterol, sphingomyelins are responsible for the fluidity of the cell membranes and the transport of substances. The functions of glycosphingolipids are also diverse. As already mentioned, the glycosphingolipids contain a glycosidically bound hexose or an oligosaccharide on the hydroxyl group of the sphingosine backbone. As a result, they have a hydrophobic ceramide component and a hydrophilic sugar component.

This sugar moiety is placed on the surface of the cell membrane, which can result in cell-cell interactions through cell adhesion. They are therefore of great importance for the signal transmission of nerve cells . But glycosphingolipids are also largely responsible for the cell interactions of the other cells.

Formation, Occurrence, Properties & Optimal Values

The biochemical synthesis of sphingolipids takes place in the endoplasmic reticulum and in the Golgi apparatus . From there they are transported to the membranes with the help of vesicles. The sphingolipids are further converted in the membranes so that they can fulfill their numerous tasks there. All cell membranes contain sphingolipids. However, their concentration is particularly high in the brain cells and nerve cells. This applies in particular to the gangliosides. For example, they make up six percent of the lipids in the gray matter of the brain .

The cerebrosides esterified with a hexose occur more frequently in the brain and liver. In the brain, the glycosidically bound sugar is mostly galactose, while the cerebrosides in the liver contain mainly glucose. The simplest sphingolipids, the ceramides, are particularly found in the skin and there in the stratum corneum (horny layer). As already mentioned, due to their amphiphilic nature, they can form a barrier there that protects the skin from water loss. Of course, the ceramides also occur in the other cell membranes, since they have to fulfill even more functions in terms of signal transmission and cell control. Sphingomyelin is also found in all cell membranes. However, its highest density is in the neurons.

Diseases & Disorders

So-called storage diseases can occur in connection with sphingolipids . These are mostly genetic diseases that are characterized by a missing or inactive enzyme . As a result, the breakdown of the corresponding sphingolipids is no longer possible. The sphingolipid accumulates in the cell and leads to its destruction.

Many storage diseases end fatally after many years of suffering. Typical lipid storage diseases include Tay-Sachs syndrome and Niemann-Pick disease . Thus, in the course of these diseases, sphingolipids are accumulated in the cells. Tay-Sachs disease is caused by an autosomal recessive mutation in a gene encoding the enzyme β-hexosaminidase A. This enzyme is responsible for breaking down the ganglioside GM2. Due to its failure, ganglioside GM2 accumulates in the nerve cells in particular. The patient suffers from central nervous and motor disorders as well as mental retardation. This disease leads to death within the first three years of life.

Niemann-Pick disease is also inherited in an autosomal recessive manner. In this disease, sphingomyelins accumulate in the cell membranes. Endothelial, mesenchymal and parenchymal cells are particularly affected. The esterification of cholesterol is also disturbed, so that this is also deposited in the cells. There are different forms of Niemann-Pick disease. These depend on the respective activity of the sphingomyelinase. In the classic form of the disease, symptoms begin during the first year of life. Death usually occurs before the end of the third year of life. If the disease begins later, symptoms develop more slowly. Then the Niemann-Pick disease is characterized by increasing enlargement of the liver and spleen , cramps ,Movement disorders , muscle tremors and mental retardation.

Another sphingolipidosis is Gaucher’s disease. Gaucher’s disease is Gaucher’s disease . Glucocerebrosides are constantly being deposited in various body cells such as the liver , spleen , bone marrow and macrophages . This disease usually leads to death by the age of two. However, Gaucher’s disease can be treated by replacing the enzyme glucocerebrosidase.

Lisa Newlon
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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.