Sphingolipids are among the building blocks of the cell membrane, along with glycerophospholipids and cholesterol. 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 backbone sphingosine, which has a fatty acid esterified to its amino group. Sphingosine is an amino alcohol containing a chain of 18 carbon atoms. 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. This results in the formation of an amphiphilic double structure with double lipid layers. The amphiphilicity is produced by the two hydrocarbon tails, which each point in the opposite direction. 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 at the hydroxyl group of the sphingosine backbone. Cerebrosides are a monohexose, whereas gangliosides have an oligosaccharose glycosidically bound.
Function, action, and roles
Sphingolipids perform different functions. Their structure plays a major role. The sphingolipids with the simplest structure, ceramides, are particularly involved in building up the horny layer of the skin. Due to their amphiphilicity, they can form a lipid bilayer which protects the skin from dehydration. In addition to this function, however, ceramides also perform numerous other tasks. These include signal transduction or tasks in the control of cell division. Sphingomyelins, along with glycerophospholipids and cholesterol, are responsible for the fluidity of cell membranes and the transport of substances. The functions of glycosphingolipids are also diverse. The glycosphingolipids contain a glycosidically bound hexose or oligosaccharide at the hydroxyl group of the sphingosine backbone, as mentioned earlier. Thus, they have a hydrophobic ceramide moiety and a hydrophilic sugar moiety. This sugar moiety is placed on the surface of the cell membrane, which can result in cell-cell interactions through cell adhesion. Therefore, they have a great importance for the signal transduction of nerve cells. However, glycosphingolipids are also significantly responsible for the cell interactions of the other cells.
Formation, occurrence, properties, and optimal values
The biochemical synthesis of sphingolipids takes place in the endoplasmic reticulum and the Golgi apparatus. From there, they are transported to membranes with the aid of vesicles. In the membranes, the sphingolipids are further transformed so that they can fulfill their numerous functions there. All cell membranes contain sphingolipids. However, their concentration is particularly high in brain cells and nerve cells. This is especially true for gangliosides. For example, they make up six percent of the lipids in the gray matter of the brain. Cerebrosides esterified with a hexose are more abundant in the brain and liver. In the brain, the glycosidically bound sugar is mostly galactose, while the cerebrosides found in the liver contain mainly glucose. The simplest sphingolipids, the ceramides, are found particularly 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 which protects the skin from water loss. Of course, ceramides are also found in the other cell membranes, as they have even more functions to perform in terms of signal transduction and cell control. Sphingomyelin is also found in all cell membranes. However, its highest density is again in neurons.
Diseases and disorders
In connection with sphingolipids, so-called storage diseases may occur. These are usually genetic diseases characterized by a missing or inactive enzyme. As a result, the degradation of the corresponding sphingolipids is no longer possible. The sphingolipid accumulates in the cell and leads to its demise. Many storage diseases end fatally after many years of suffering.Typical lipid storage diseases include Tay-Sachs syndrome and Niemann-Pick disease. In the course of these diseases, sphingolipids are thus accumulated in the cells. Tay-Sachs disease is caused by an autosomal recessive mutation of a gene encoding the enzyme β-hexosaminidase A. This enzyme is responsible for the degradation of the ganglioside GM2. Due to its failure, ganglioside GM2 accumulates especially in neurons. The patient suffers from central nervous and motor disorders as well as mental retardation. Within the first three years of life, this disease leads to death. Niemann-Pick disease is also inherited in an autosomal recessive manner. In this disease, sphingomyelins accumulate in 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 various 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 starts later, the symptoms develop more slowly. Then Niemann-Pick disease is characterized by increasing liver and spleen enlargement, convulsions, movement disorders, muscle tremors and mental retardation. Another sphingolipidosis is Gaucher’s disease. Gaucher’s disease is Gaucher’s disease. Glucocerebrosides are constantly deposited in various body cells such as liver, spleen, bone marrow and macrophages. In most cases, this disease leads to death at the age of two. However, Gaucher’s disease can be treated the replacement of the enzyme glucocerebrosidase.
