Phospholipids are amphiphilic molecules; their fatty acid residues are strongly lipophilic, while their charged head group is hydrophilic. Of the two fatty acids, one is generally unsaturated (i.e. one or more double bonds are present). As the single phospholipids constantly rotate, the fatty acid, which is kinked due to the inflexible double bond, has a significantly greater radius than that of two saturated fatty acids. This increases the fluidity of the biomembrane, and the formation of paracrystalline structures is avoided. In bacterial or yeast cells that are exposed to different temperatures, the fluidity is constantly adjusted according to the surrounding temperatures by incorporation of phospholipids with different lengths of fatty acid residues, with or without double bonds. Also fishes, living in cold waters, have a higher content of unsaturated fatty acids than those living in warm tropical waters.
In addition to the membrane lipids that are derivatives of glycerol, animal cells contain additional lipids and phospholipids. These have the amino alcohol sphingosine as a base and are referred to as sphingolipids. The N‐acyl fatty acid derivatives of sphingosine are termed ceramides. Sphingomyelin, one of the most important of the sphingolipids, has a structure analogous to that of phosphatidylcholine (Figure 2.3). It is very common in the myelin sheaths found around the axons of neurons.
If the sphingomyelin head group is substituted with a sugar residue (e.g. galactose or glucose), a cerebroside results. These membrane lipids are missing the phosphate residue and are therefore uncharged. Cerebrosides are common in the brain, where they are oriented toward the cell exterior. Gangliosides are sphingolipids with an especially complex structure. They contain oligosaccharides and at least one sialic acid unit (Figure 2.4). In the brain, 6% of lipids are present in the form of gangliosides. Sphingolipid storage diseases (e.g. Tay–Sachs disease), which result in early neurological deterioration, are of great medical importance.
Figure 2.4 Chemical structure of cerebrosides (glycolipids). (a) Galactocerebroside and (b) ganglioside (GM2).
Phospholipids are cleaved by different phospholipases. Phospholipase A2 cleaves the central fatty acid at C2 of glycerol residues. The resulting lysophospholipid can lyse cell membranes; interestingly, many snake venoms contain high dosages of phospholipase A2. Phospholipase A1 hydrolyzes the fatty acid at C1 of glycerol, while phospholipase C opens the phosphate ester bonds with glycerol.
A pharmacologically important lipid class, the eicosanoids, is only mentioned briefly here. To summarize, this class includes prostaglandins, thromboxanes, and leukotrienes. These play many roles and act as paracrine mediators (e.g. in pain, fever, inflammation, blood pressure, and blood coagulation). Phospholipase A2 releases arachidonic acid from phosphatidylcholine, which contains the fourfold unsaturated arachidonic acid in its C2 position. Arachidonic acid is converted into prostaglandin (e.g. example by cyclooxygenase). This enzyme is an important target for many drugs (the so‐called nonsteroidal anti‐inflammatory drugs [NSAIDs]), among which aspirin (acetylsalicylic acid) is the most famous. Inflammation can also be effectively suppressed by inhibiting the expression of phospholipase A2 by corticoids (e.g. cortisone medications).
Triacylglycerides, not phospholipids, are present in the storage tissue of plants and animals. These are broken down by lipases.
The steroid cholesterol (Figure 2.5) is an important and common building block of animal membranes (it is missing in the membranes of bacteria, fungi, and plants). It is stored in the membrane, parallel to the phospholipids (Figure 2.2), with its polar hydroxyl group oriented toward the cell exterior. Cholesterol is a stiff molecule that stabilizes biological membranes and lowers their fluidity and permeability. In biological membranes, local assemblies of membrane proteins usually rich in cholesterol, known as rafts, have been found. Cholesterol is transported as cholesteryl ester, such as cholesterol‐3‐stearate in lipoproteins (see Chapter 5.4).
Figure 2.5 Cholesterol and related sterols. Cholesterol; β‐sitosterol replaces cholesterol in plants; ergosterol is present in the membranes of fungi; testosterone; β‐estradiol; cortisol; aldosterone; active vitamin D.
Cholesterol can be synthesized in the body; the biggest portion, however, is obtained from food. It is important not only to build up membranes but also as a precursor for the synthesis of important hormones and vitamins (Figure 2.5):
Glucocorticoids. For example, cortisol (from the adrenal gland) influences the metabolism of carbohydrates, proteins, and lipids; cortisol inhibits phospholipase A2, induces several genes such as the transcription factor NF‐κB, and thus suppresses inflammation processes.
Mineralocorticoids. For example, aldosterone (from the adrenal gland) regulates the secretion of salt and water through the kidneys.
Sexual
