By definition, lipids are water-insoluble biomolecules that are highly soluble in organic solvents such as chloroform. Lipids have a variety of biological roles: they serve as fuel molecules, highly concentrated energy stores, signal molecules and messengers in signal-transduction pathways, and components of membranes. The first three roles of lipids will be considered in later chapters. Here, our focus is on lipids as membrane constituents. The three major kinds of membrane lipids are phospholipids, glycolipids, and cholesterol. We begin with lipids found in eukaryotes and bacteria. The lipids in archaea are distinct, although they have many features related to membrane formation in common with lipids of other organisms.

Phospholipids are abundant in all biological membranes. A phospholipid molecule is constructed from four components: one or more fatty acids, a platform to which the fatty acids are attached, a phosphate, and an alcohol attached to the phosphate (Figure 12.3). The fatty acid components provide a hydrophobic barrier, whereas the remainder of the molecule has hydrophilic properties that enable interaction with the aqueous environment.

The platform on which phospholipids are built may be glycerol, a three-carbon alcohol, or sphingosine, a more complex alcohol. Phospholipids derived from glycerol are called phosphoglycerides. A phosphoglyceride consists of a glycerol backbone to which are attached two fatty acid chains and a phosphorylated alcohol.

In phosphoglycerides, the hydroxyl groups at C-1 and C-2 of glycerol are esterified to the carboxyl groups of the two fatty acid chains. The C-3 hydroxyl group of the glycerol backbone is esterified to phosphoric acid. When no further additions are made, the resulting compound is phosphatidate (diacylglycerol 3-phosphate), the simplest phosphoglyceride. Only small amounts of phosphatidate are present in membranes. However, the molecule is a key intermediate in the biosynthesis of the other phosphoglycerides (Section 26.1). The absolute configuration of the glycerol 3-phosphate moiety of membrane lipids is shown in Figure 12.4.

The major phosphoglycerides are derived from phosphatidate by the formation of an ester bond between the phosphate group of phosphatidate and the hydroxyl group of one of several alcohols. The common alcohol moieties of phosphoglycerides are the amino acid serine, ethanolamine, choline, glycerol, and inositol.

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The structural formulas of phosphatidylcholine and the other principal phosphoglycerides—namely, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and diphosphatidylglycerol—are given in Figure 12.5.

Sphingomyelin is a phospholipid found in membranes that is not derived from glycerol. Instead, the backbone in sphingomyelin is sphingosine, an amino alcohol that contains a long, unsaturated hydrocarbon chain (Figure 12.6). In sphingomyelin, the amino group of the sphingosine backbone is linked to a fatty acid by an amide bond. In addition, the primary hydroxyl group of sphingosine is esterified to phosphorylcholine.

The second major class of membrane lipids, glycolipids, are sugar-containing lipids. Like sphingomyelin, the glycolipids in animal cells are derived from sphingosine. The amino group of the sphingosine backbone is acylated by a fatty acid, as in sphingomyelin. Glycolipids differ from sphingomyelin in the identity of the unit that is linked to the primary hydroxyl group of the sphingosine backbone. In glycolipids, one or more sugars (rather than phosphorylcholine) are attached to this group. The simplest glycolipid, called a cerebroside, contains a single sugar residue, either glucose or galactose.

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More-complex glycolipids, such as gangliosides, contain a branched chain of as many as seven sugar residues. Glycolipids are oriented in a completely asymmetric fashion with the sugar residues always on the extracellular side of the membrane.

Cholesterol, the third major type of membrane lipid, has a structure that is quite different from that of phospholipids. It is a steroid, built from four linked hydrocarbon rings.

A hydrocarbon tail is linked to the steroid at one end, and a hydroxyl group is attached at the other end. In membranes, the orientation of the molecule is parallel to the fatty acid chains of the phospholipids, and the hydroxyl group interacts with the nearby phospholipid head groups. Cholesterol is absent from prokaryotes but is found to varying degrees in virtually all animal membranes. It constitutes almost 25% of the membrane lipids in certain nerve cells but is essentially absent from some intracellular membranes.

The membranes of archaea differ in composition from those of eukaryotes or bacteria in three important ways. Two of these differences clearly relate to the hostile living conditions of many archaea (Figure 12.7). First, the nonpolar chains are joined to a glycerol backbone by ether rather than ester linkages. The ether linkage is more resistant to hydrolysis. Second, the alkyl chains are branched rather than linear. They are built up from repeats of a fully saturated five-carbon fragment. These branched, saturated hydrocarbons are more resistant to oxidation than the unbranched chains of eukaryotic and bacterial membrane lipids. The ability of archaeal lipids to resist hydrolysis and oxidation may help these organisms to withstand the extreme conditions, such as high temperature, low pH, or high salt concentration, under which some of these archaea grow. Finally, the stereochemistry of the central glycerol is inverted compared with that shown in Figure 12.4.

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The repertoire of membrane lipids is extensive. However, these lipids possess a critical common structural theme: membrane lipids are amphipathic molecules (amphiphilic molecules), that is, they contain both a hydrophilic and a hydrophobic moiety.

Let us look at a model of a phosphoglyceride, such as phosphatidylcholine. Its overall shape is roughly rectangular (Figure 12.8A). The two hydrophobic fatty acid chains are approximately parallel to each other, whereas the hydrophilic phosphorylcholine moiety points in the opposite direction. Sphingomyelin has a similar conformation, as does the archaeal lipid depicted. Therefore, the following shorthand has been adopted to represent these membrane lipids: the hydrophilic unit, also called the polar head group, is represented by a circle, and the hydrocarbon tails are depicted by straight or wavy lines (Figure 12.8B).

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