Human Biochemistry Volume 2 - Murray R. 1993

Biochemistry of Intra- and Intercellular Communication
Membranes: Structure, Assembly, and Function
Lipid Composition

Most Lipids in mammalian membranes are represented by Phospholipids, glycosphingolipids, and Cholesterol.

Phospholipids

Membrane phospholipids are divided into two main groups. Phosphoglycerides are the most common, consisting of a glycerol backbone esterified to two fatty acid molecules and a phosphorylated alcohol (Fig. 42.2). The Fatty acids typically contain an even number of carbon atoms, mostly 14 or 16. Their carbon chains are unbranched and can be either saturated or unsaturated. The simplest phosphoglyceride is phosphatidic acid—1, 2-diacylglycerol-3-phosphate—which is a key intermediate in the synthesis of all other phospholipids (see Ch. 25). In other phospholipids, the phosphate group is esterified with the hydroxyl group of compounds such as ethanolamine, Choline, Serine, glycerol, or Inositol.

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Fig. 42.1. Protein-to-lipid ratio in various membranes. The amount of protein equals or exceeds the amount of lipid in almost all membranes. The only exception to this rule is myelin, an electrical insulator found in many nerve fibers. (From Singer S. J.: Architecture and topography of biologic membranes. Chapter 4 In: Cell Membranes: Biochemistry, Cell Biology and Pathology, Weissman G., Claiborne R. [editors] HP Publishing Co, 1975, with kind permission.)

The second class of phospholipids is represented by sphingomyelins, which contain a sphingosine residue instead of glycerol. The fatty acid is attached to the amino group of sphingosine via an amide bond. The primary hydroxyl group of sphingosine is esterified with phosphorylcholine (see p. 157). As their name implies, sphingomyelins are a major component of the myelin sheath.

Fig. 42.2. Phosphoglyceride consisting of fatty acid residues (R₁ and R₂), glycerol, and a phosphorylated alcohol moiety. In phosphatidic acid, R₃ is a hydrogen atom.

Glycosphingolipids

Glycosphingolipids are lipids containing sugar residues. This group includes cerebrosides and gangliosides, as well as sphingosine derivatives. Cerebrosides and gangliosides differ from sphingomyelin in the specific groups attached to the primary hydroxyl group of sphingosine. In sphingomyelin, phosphocholine is attached to the alcohol group, whereas cerebrosides contain a hexose residue, either glucose or galactose, at this position (see p. 157). Gangliosides contain a chain of three or more sugars, with at least one of them being sialic acid linked to the primary alcohol group of sphingosine.

Sterols

The most abundant sterol in membranes is cholesterol, which is found almost exclusively in The Plasma Membrane of mammalian Cells, though smaller amounts may also be present in Mitochondria, Golgi membranes, and nuclear membranes. Cholesterol content typically increases toward the outer leaflet of the plasma membrane. Cholesterol inserts between phospholipid molecules, with its hydroxyl group interacting with the aqueous phase and the rest of the molecule embedded within the hydrophobic layer. At temperatures above the phase transition Temperature (see the Description of the fluid-mosaic model), its rigid sterol ring interacts with the acyl groups of phospholipids, restricting their mobility and thereby decreasing membrane fluidity. Conversely, at temperatures close to the phase transition, the interaction of cholesterol with acyl chains prevents them from packing tightly together. As a result, the temperature at which the liquid-gel transition occurs is lowered, which helps maintain membrane fluidity at lower temperatures.

Amphipathic Nature of Membranes

All major Membrane Lipids contain both hydrophobic and hydrophilic regions and are therefore termed amphipathic compounds. Consequently, membranes are also amphipathic. If the core of a molecule were composed of hydrophobic groups, it would be insoluble in Water and soluble in oils. Conversely, if the core consisted of hydrophilic regions, it would be insoluble in oils and soluble in water. Amphipathic membrane lipids contain a polar "HEAD" and nonpolar "tails" (Fig. 42.3).

Fig. 42.3. Schematic representation of a phospholipid or other membrane lipid. The polar head is hydrophilic, whereas the hydrocarbon tails are hydrophobic or lipophilic. The fatty acid tails may be saturated (S) or unsaturated (U); the former are typically attached to carbon atom 1 of the glycerol residue, and the latter to carbon atom 2.

Saturated fatty acid tails adopt an extended conformation, whereas unsaturated tails, which exist predominantly in the cis conformation within the membrane, can introduce kinks. The greater the number of such kinks, the less tightly packed the lipids are in the membrane and, consequently, the higher its fluidity. Amphipathic compounds such as detergents play an important role in both biochemistry and everyday life. Their Structure is not all that different from that of lipids.