## 3 Role of Lipids for Membrane Function and Intracellular Transport
### Lipid Classes and Species  
Membrane lipids are grouped into different classes based on different head groups, such as the main phospholipid (PL) classes: Phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidic acid (PA). Each of the PL classes consists of many lipid species due to various compositions of fatty acyl groups, with different numbers of carbon atoms and double bonds (Figure 5). Thus, cells contain several thousands of different lipid species. With modern mass spectrometry (MS) analyses, it is possible to quantify several hundred or close to a thousand lipid species in one sample [128; 129]. Most PLs contain ester-bound fatty acyl groups, but ether-linked PLs may constitute 5-20% of the lipids in some cells and are often referred to as \"the forgotten lipids.\" Most PLs contain C16 or C18 fatty acyl groups with zero, one, or two double bonds, although longer carbon chains with more double bonds (e.g., 20:4 and 22:6) are also common in some PL classes. For a recent and detailed review article describing the diversity of membrane lipids, see [130]. The biosynthesis of PLs and sphingolipids and where the different parts of these lipids are synthesized were reviewed and illustrated by the authors of [131]. Shiga toxin binds to the glycosphingolipid Gb3. Gb3 is synthesized from ceramide, and the structure of Gb3 and the precursors GlcCer and LacCer are shown in Figure 6. As shown in Figure 5, the sphingolipids differ from the PLs, as they have a sphingoid base backbone. Whereas the hydrophobic chains of the PLs are linked to a glycerol unit, the sphingolipids contain an N-amidated fatty acyl chain, where the N atom originates from serine. The fatty acyl groups of sphingolipids differ considerably from those in PLs and contain fatty acyl groups with 16 to 26 carbon atoms [133; 134]. The most common glycosphingolipid species contain N-amidated C16:0, C24:0, and C24:1 (and some cells also have considerable amounts of C22:0) [33; 82]. Although C16:0 is common also in PLs, C24:0 and C24:1 have not been reported to be present in PLs to our knowledge. Moreover, monounsaturated fatty acyl groups with 16-20 carbon atoms seem to be absent in glycosphingolipids [6; 135]. However, minor amounts of Gb3 containing C18:1 were recently reported in H1299 cells [136]. Since the glycosphingolipids normally contain very little of species with N-amidated C18 and C20 fatty acyl groups, the glycosphingolipids have a bimodal distribution regarding the fatty acyl chain length [82], which is further discussed below. Figure 5: Illustrations of some lipid structures. On the top, cholesterol (CHOL) is shown, followed by PC 16:0/16:0, which is a lipid species often used in model membranes. However, although PC species are very common in cells, PLs normally contain very little of species with two saturated fatty acyl groups. PS 18:0/18:1 is an example of a PL with 1 saturated and 1 unsaturated fatty acyl group, which is the most common combination of fatty acyl groups in all PL classes. Note that all double bonds in PLs are in a _cis_-configuration and that the unsaturated fatty acyl group is most often found in the _st-2_ position. PE-P 18:0/20:4 is an example of a plasmalogen, i.e., an ether lipid with an alkenyl group, and these lipids often contain polyunsaturated fatty acyl groups in the _sn-2_ position. The sphingolipid SM d18:1/24:1 is shown with the sphingosine part marked in pink. Note that the N-amidated fatty acyl group is so long that it can theoretically penetrate approximately halfway into the opposite leaflet. These structures were made using the drawing tool available at Lipid Maps ([[https://www.lipidmaps.org/](https://www.lipidmaps.org/)]([https://www.lipidmaps.org/](https://www.lipidmaps.org/)) (accessed on 24 May 2021)). Reprinted from the open-access review [132]. Membrane lipids are amphiphilic with a hydrophilic head and hydrophobic tails.