Chapter 2: Chemical Foundations

Phospholipids Associate Noncovalently to Form the Basic Bilayer Structure of Biomembranes

Biomembranes are large, flexible sheets with a two-ply, or bilayer, structure. They serve as the boundaries of cells and their intracellular organelles and form the outer surfaces of some viruses. Membranes literally define what is a cell (the outer membrane and the contents within the membrane) and what is not (the extracellular space outside the membrane). Unlike proteins, nucleic acids, and polysaccharides, membranes are assembled by the noncovalent association of their component building blocks. The primary building blocks of all biomembranes are phospholipids, whose physical properties are responsible for the formation of the sheet-like bilayer structure of membranes. In addition to phospholipids, biomembranes can contain a variety of other molecules, including cholesterol, glycolipids, and proteins. The structure and functions of biomembranes will be described in detail in Chapter 7. Here we will focus on the phospholipids in biomembranes.

To understand the structure a phospholipid molecule, we have to understand each of its component parts and how it is assembled. As we will see shortly, a phospholipid molecule consists of two long-chain, nonpolar fatty acid groups linked (usually by an ester bond) to small, highly polar groups, including a short organic molecule such as glycerol (trihydroxy propane), a phosphate, and typically, a small organic molecule (Figure 2-20).

FIGURE 2-20 Phosphatidylcholine, a typical phosphoglyceride. All phosphoglycerides are amphipathic phospholipids, having a hydrophobic tail (yellow) and a hydrophilic head (blue) in which glycerol is linked via a phosphate group to an alcohol. Either or both of the fatty acyl side chains in a phosphoglyceride may be saturated or unsaturated. In phosphatidic acid (red), the simplest phospholipid, the phosphate is not linked to an alcohol.

Fatty acids consist of a hydrocarbon chain attached to a carboxyl group (–COOH). Like glucose, fatty acids are an important energy source for many cells (see Chapter 12). They differ in length, although the predominant fatty acids in cells have an even number of carbon atoms, usually 14, 16, 18, or 20. The major fatty acids in phospholipids are listed in Table 2-4. Fatty acids are often designated by the abbreviation Cx:y, where x is the number of carbons in the chain and y is the number of double bonds. Fatty acids containing 12 or more carbon atoms are nearly insoluble in aqueous solutions because of their long hydrophobic hydrocarbon chains.

Fatty acids in which all the carbon-carbon bonds are single bonds—that is, the fatty acids have no carbon-carbon double bonds—are said to be saturated; those with at least one carbon-carbon double bond are called unsaturated. Unsaturated fatty acids with more than one carbon-carbon double bond are referred to as polyunsaturated. Two “essential” polyunsaturated fatty acids, linoleic acid (C18:2) and linolenic acid (C18:3), cannot be synthesized by mammals and must be supplied in their diet. Mammals can synthesize other common fatty acids.

In phospholipids, fatty acids are covalently attached to another molecule by esterification. In the combined molecule formed by this reaction, the part derived from the fatty acid is called an acyl group, or fatty acyl group. This structure is illustrated by the most common forms of phospholipids: phosphoglycerides, which contain two acyl groups attached to two of the three hydroxyl groups of glycerol (see Figure 2-20).

In phosphoglycerides, one hydroxyl group of the glycerol is esterified to phosphate while the other two are normally esterified to fatty acids. The simplest phospholipid, phosphatidic acid, contains only these components. Phospholipids such as phosphatidic acids are not only membrane building blocks but also important signaling molecules. Lysophosphatidic acid, in which the acyl chain at the 2 position (attached to the hydroxyl group on the central carbon of the glycerol) has been removed, is relatively water soluble and can be a potent inducer of cell division (called a mitogen). In most phospholipids found in membranes, the phosphate group is also esterified to a hydroxyl group on another hydrophilic compound. In phosphatidylcholine, for example, choline is attached to the phosphate (see Figure 2-20). The negatively charged phosphate, as well as the charged or polar groups esterified to it, can interact strongly with water. The phosphate and its associated esterified group constitute the “head” group of a phospholipid, which is hydrophilic, whereas the fatty acyl chains, the “tails,” are hydrophobic. Other common phosphoglycerides and associated head groups are shown in Table 2-5. Molecules such as phospholipids that have both hydrophobic and hydrophilic regions are called amphipathic. In Chapter 7, we will see how the amphipathic properties of phospholipids allow their assembly into sheet-like bilayers in which the fatty acyl tails point into the center of the sheet and the head groups point outward toward the aqueous environment (see Figure 2-13).

Fatty acyl groups also can be covalently linked in other fatty molecules, including triacylglycerols, or triglycerides, which contain three acyl groups esterified to glycerol:

They also can be covalently attached to the very hydrophobic molecule cholesterol, an alcohol, to form cholesteryl esters:

Triglycerides and cholesteryl esters are extremely water-insoluble molecules in which fatty acids and cholesterol are either stored or transported. Triglycerides are the storage form of fatty acids in the fat cells of adipose tissue and are the principal components of dietary fats. Cholesteryl esters and triglycerides are transported between tissues through the bloodstream in specialized carriers called lipoproteins (see Chapter 14).

We saw above that the fatty acids, which are key components of both phospholipids and triglycerides, can be either saturated or unsaturated. An important consequence of the carbon-carbon double bond (C=C) in an unsaturated fatty acid is that two stereoisomeric configurations, cis and trans, are possible around each of these bonds:

A cis double bond introduces a rigid kink in the otherwise flexible straight acyl chain of a saturated fatty acid (Figure 2-21). In general, the unsaturated fatty acids in biological systems contain only cis double bonds. Saturated fatty acids without the kink can pack together tightly and so have higher melting points than unsaturated fatty acids. The main fatty molecules in butter are triglycerides with saturated fatty acyl chains, which is why butter is usually solid at room temperature. Unsaturated fatty acids or fatty acyl chains with the cis double bond kink cannot pack as closely together as saturated fatty acyl chains. Thus vegetable oils, composed of triglycerides with unsaturated fatty acyl groups, usually are liquid at room temperature. Vegetable and similar oils may be partially hydrogenated to convert some of their unsaturated fatty acyl chains to saturated fatty acyl chains. As a consequence, the hydrogenated vegetable oil can be molded into solid sticks of margarine. A by-product of the hydrogenation reaction is the conversion of some of the fatty acyl chains into trans fatty acids, popularly called “trans fats.” These “trans fats,” found in partially hydrogenated margarine and other food products, are not natural. Saturated and trans fatty acids have similar physical properties; for example, they tend to be solids at room temperature. Their consumption, relative to the consumption of unsaturated fats, is associated with increased plasma cholesterol levels and is discouraged by some nutritionists.

FIGURE 2-21 The effect of a double bond on the shape of fatty acids. Shown are chemical structures of the ionized form of palmitic acid, a saturated fatty acid with 16 C atoms, and oleic acid, an unsaturated one with 18 C atoms. In saturated fatty acids, the hydrocarbon chain is often linear; the cis double bond in oleate creates a rigid kink in the hydrocarbon chain.