Sphingolipids
Different residues (R) result in different subgroups:
R = hydrogen : ceramides
R = phosphocholine : sphingomyelins
R = saccharide : glycosphingolipids
Sphingolipids are important components of the cell membrane and belong to the compound class of polar lipids . In contrast to the glycerine- based phosphoglycerides , the sphingolipids are derived from the unsaturated amino alcohol sphingosine .
properties
Sphingolipids are often found in nerve tissue , where they play an important role in signal transduction and the interaction of individual cells . The essential lipids in the eukaryotic cell membrane include glycerophospholipids , cholesterol and sphingolipids (phospho- and glycosphingolipids). Their functions can be described on the one hand by the structure and regulation of the fluidity of cellular membranes and on the other hand by explaining intercellular recognition processes (see multicellular cells ). In clinical and medical applications, their analysis is used to characterize them as development-specific markers, but also as tumors and blood group antigens .
In the mid-1980s, the inhibition of protein kinase C (PKC) by sphingosine was discovered . This led to the idea that sphingolipids can also function as intracellular messenger substances, so-called second messengers . Current research interests focus on the sphingolipids ceramide or ceramide-1-phosphate and sphingosine or sphingosine-1-phosphate.
Sphingosine is amidically linked to an acyl group such as a fatty acid via its amine group . Because of the amine group, sphingolipids accumulate in acidic organelles because they are protonated and can then no longer diffuse freely between the two layers of the lipid bilayer of a biomembrane .
An incorrect breakdown of the sphingolipids is known as sphingolipidosis .
biosynthesis
Sphingolipids are synthesized within a cell in the endoplasmic reticulum and in the Golgi apparatus , but are further processed in the plasma membrane and in endosomes , where they perform numerous tasks. They are transported via vesicles . Sphingolipids are virtually undetectable in the mitochondria and the endoplasmic reticulum, but their concentration in the plasma membrane is 20–35 mol%.
From the amino acid serine and an acyl-CoA , the serine palmitoyltransferase produces 3-ketodihydrosphingosine . Subsequently, dihydrosphingosine is formed by the 3-ketodihydrosphingosine reductase and dihydroceramide is subsequently formed by the ceramide synthase . From this, the basic body of the ceramides can be formed by the dihydroceramide desaturase . 4 different metabolites can be formed from ceramides. Sphingosine can be formed from ceramides by the ceramide synthase , which is converted into sphingosine-1-phosphate by the sphingosine kinase , which in turn can then be modified with ethanolamine and a fatty aldehyde . Sphingomyelin can also be produced from ceramides through the sphingomyelin synthase . Furthermore, ceramide-1-phosphate can be formed from ceramides by the ceramide kinase . In addition, glycosphingolipids can be formed from ceramides .
Classes of sphingolipids
There are three main types of sphingolipids: ceramides and the sphingomyelins and glycosphingolipids derived from them . The latter are further divided into cerebrosides and gangliosides . These types differ in the nature of their rest (see picture).
Ceramides are the simplest group of sphingolipids. The remainder of them is only formed by a hydrogen atom , so they are just a sphingosine molecule that is bound to a fatty acid by an amide bond. Sphingomyelins have a phosphocholine or phosphoethanolamine molecule that is bound as an ester to the 1- hydroxyl group of a ceramide. Glycosphingolipids are ceramides with one or more sugar residues that are bound to the 1-hydroxy group through a β- glycoside bond . Cerebrosides have a single glucose or galactose molecule as a remainder, while gangliosides contain at least three sugars, at least one of which is sialic acid .
Web links
- SphinGOMAP - site on the topic, including an extensive systematic map of sphingolipid metabolism
- d'Eustachio / reactome: Sphingolipid metabolism , doi : 10.3180 / REACT_19323.1
Individual evidence
- ↑ JP Slotte: Sphingomyelin-cholesterol interactions in biological and model membranes. In: Chem Phys Lipids Volume 102, Number 1-2, 1999, pp. 13-27.
- ^ Charles Chalfant: Sphingolipids as Signaling and Regulatory Molecules. Springer Science & Business Media, 2011, ISBN 978-1-441-96741-1 , p. 3.
- ↑ van Meer G Lisman Q: sphingolipid transport: rafts and trans locators . In: J. Biol. Chem. . 277, No. 29, July 2002, pp. 25855-8. doi : 10.1074 / jbc.R200010200 . PMID 12011105 .
- ↑ a b c d e f g h L. Ashley Cowart: Sphingolipids and Metabolic Disease. Springer Science & Business Media, 2011, ISBN 978-1-461-40650-1 , p. 2.