MCAT Biochemistry Review

Chapter 5: Lipid Structure and Function

Introduction

What do beer, human eyes, and sperm whales have in common? For all of these, lipids play a key role in some of their most interesting characteristics. The taste and smell of hops comes from lipids called terpenes. The ability of the human eye to respond to light (and therefore see) relies heavily on retinal, a lipid derived from vitamin A. Sperm whales use an enormous reservoir of spermaceti to dive to a depth of up to three kilometers to hunt giant squid. Spermaceti is a lipid with a density that changes dramatically with temperature—effectively allowing sperm whales to adjust their density with depth so that they can stay at depth without having to constantly fight buoyancy.

Lipids, as a class, are characterized by insolubility in water and solubility in nonpolar organic solvents. Aside from this shared feature, lipids diverge dramatically in their structural organization and biological functions, serving vital structural, signaling, and energy storage roles. In this chapter, we will explore the structural and functional characteristics of each of the major categories of lipids tested on the MCAT.

As structural building blocks, we will investigate phospholipids and sterols, which make up vesicles, liposomes, and membranes. When it comes to signaling, we will note that lipids serve multiple roles, from enzyme cofactors to light-absorbing pigments, and from intracellular messengers to hormones. Finally, we will see that lipids are the workhorse of energy storage, giving the most “bang” for the metabolic “buck” by weight.

5.1 Structural Lipids

Lipids are the major component of the phospholipid bilayer, one of the most important structural parts of the cell. The unique ability of phospholipids to form a bilayer allows our cells to function as they do, separating the cell interior from the surrounding environment. We will first take a close look at the structure and role of phospholipids, glycerophospholipids, and sphingolipids. Finally, we will review the gross structural characteristics of the unique class called waxes.

Each of the membrane components is an amphipathic molecule, meaning that it has both hydrophilic and hydrophobic regions. For these membrane lipids, the polar head is the hydrophilic region, whereas the fatty acid tails are the hydrophobic region. When placed in aqueous solution, these molecules spontaneously form structures that allow the hydrophobic regions to group internally while the hydrophilic regions interact with water. This leads to the formation of various structures, including micelles, liposomes, and the phospholipid bilayer, shown in Figure 5.1.

Figure 5.1. Membrane Lipids Form Various Stuctures in Aqueous Solutions

BRIDGE

Although phospholipids are indeed the largest component of the phospholipid bilayer, nonphospholipids like glycolipids also play a role—and can be an important part of processes like cell recognition and signaling, discussed in Chapter 3 of MCAT Biochemistry Review.

PHOSPHOLIPIDS

Phospholipids contain the following elements: a phosphate and alcohol that comprise the polar head group, joined to a hydrophobic fatty acid tail by phosphodiester linkages. One or more fatty acids are attached to a backbone to form the hydrophobic tail region. Phospholipids can be further classified according to the backbone on which the molecule is built. For example, glycerol, a three-carbon alcohol, forms phosphoglycerides or glycerophospholipids, and sphingolipids have a sphingosine backbone. One important thing to note, however, is that not all sphingolipids are phospholipids, as described later in this chapter.

One thing that these lipids do all share in common is a tail composed of long-chain fatty acids. These hydrocarbon chains vary by their degree of saturation and length. These two properties determine how the overall molecule will behave. Fully saturated fatty acid tails will have only single bonds; the carbon atom is considered saturated when it is bonded to four other atoms, with no π bonds. Saturated fatty acids, such as those in butter, have greater van der Waals forces and a more stable overall structure. Therefore, they form solids at room temperature. An unsaturated fatty acid includes one or more double bonds. Double bonds introduce kinks into the fatty acid chain, which makes it difficult for them to stack and solidify. Therefore, unsaturated fats—like olive oil—tend to be liquids at room temperature. The same rules apply in the phospholipid bilayer: phospholipids with unsaturated fatty acid tails make up more fluid regions of the phospholipid bilayer. Phospholipids, glycerophospholipids, and sphingolipids can have any of a variety of fatty acid tails and also different head groups, which determine their properties at the surface of the cell membrane. The next two sections—glycerophospholipids and sphingolipids—focus on the various polar head groups that different phospholipids may have.

KEY CONCEPT

Lipid properties—for all categories of lipids—are determined by the degree of saturation in fatty acid chains and the functional groups to which the fatty acid chains are bound.

GLYCEROPHOSPHOLIPIDS

As mentioned in the last section, glycerophospholipids are all phospholipids; yet, not all phospholipids are glycerophospholipids! Glycerophospholipids (or phosphoglycerides) are specifically those phospholipids that contain a glycerol backbone bound by ester linkages to two fatty acids and by a phosphodiester linkage to a highly polar head group, as shown in Figure 5.2. Because the head group determines the membrane surface properties, glycerophospholipids are named according to their head group. For example, phosphatidylcholine is the name of a glycerophospholipid with a choline head group, and phosphatidylethanolamine is one with an ethanolamine head group. The head group can be positively charged, negatively charged, or neutral. The membrane surface properties of these molecules make them very important to cell recognition, signaling, and binding. Within each subtype, the fatty acid chains can vary in length and saturation, resulting in an astounding variety of functions that are the focus of active scientific research.

Figure 5.2. Structure of a Glycerophospholipid X denotes the head group connected to the glycerol backbone by a phosphodiester linkage.

SPHINGOLIPIDS

Blood typing makes it possible to give life-saving blood transfusions without risking potentially fatal acute hemolytic reactions. The ABO blood typing system is based on cell-surface antigens on red blood cells. These cell-surface antigens are some of the most well-known sphingolipids. Like glycerophospholipids, sphingolipids are also sites of biological recognition at the cell surface and can be bound to various head groups and fatty acids.

REAL WORLD

Although experiments in blood transfusion are recorded as early as the 17th century, blood typing wasn't developed until the 20th century. With the advent of the ABO and Rh factor blood typing systems, blood transfusions could now be successfully administered to patients with hemophilia (a clotting disorder that causes significant bleeding), during surgery, and in a number of other applications.

Sphingolipids have a sphingosine or sphingoid (sphingosine-like) backbone, as opposed to the glycerol backbone of glycerophospholipids. These molecules also have long-chain, nonpolar fatty acid tails and polar head groups. Many sphingolipids are also phospholipids because they contain a phosphodiester linkage. However, other sphingolipids contain glycosidic linkages to sugars; any lipid linked to a sugar can be termed a glycolipid. Sphingolipids are divided into four major subclasses, differing by their head group.

The simplest sphingolipid is ceramide, which has a single hydrogen atom as its head group.

Sphingomyelins are the major class of sphingolipids that are also phospholipids (sphingophospholipids). These molecules have either phosphatidylcholine or phosphatidylethanolamine as a head group, and are thus bound by a phosphodiester bond. Sphingomyelin head groups have no net charge. As the name implies, sphingomyelins are major components in the plasma membranes of cells producing myelin (oligodendrocytes and Schwann cells), the insulating sheath for axons.

Sphingolipids with head groups composed of sugars bound by glycosidic linkages are considered glycolipids, as mentioned above, or, more specifically, glycosphingolipids. These molecules are not phospholipids because they contain no phosphodiester linkage. Glycosphingolipids are found mainly on the outer surface of the plasma membrane and can be further classified as cerebrosides or globosidesCerebrosides have a single sugar, whereas globosides have two or more. These molecules are also referred to as neutral glycolipids because they have no net charge at physiological pH.

The final group is composed of the most complex sphingolipids. Gangliosides are glycolipids that have polar head groups composed of oligosaccharides with one or more N-acetylneuraminic acid (NANA; also called sialic acid) molecules at the terminus, and a negative charge. These molecules are also considered glycolipids because they have a glycosidic linkage and no phosphate group. Gangliosides play a major role in cell interaction, recognition, and signal transduction.

MNEMONIC

Gangliosides are the “gangly” sphingolipids, with the most complex structure and functional groups (oligosaccharides and NANA) in all directions.

A summary of the different types of sphingolipids is provided in Figure 5.3.

Figure 5.3. Types of Sphingolipids Ceramide has a single hydrogen atom for a head group; sphingomyelins have phosphodiester linkages (phospholipids); cerebrosides have one sugar; globosides (not pictured) have multiple sugars; gangliosides have oligosaccharides and terminal sialic acids.

REAL WORLD

Sphingolipid accumulation is associated with numerous pathological conditions. Sphingomyelins found in the myelin sheath help in signal transduction. Accumulation of sphingomyelin, resulting from the lack of the enzyme sphingomyelinase, can result in Niemann–Pick disease. Symptoms can include mental retardation and seizures. Sulfatides are sulfated cere-brosides associated with Alzheimer's disease.

WAXES

Waxes are esters of long-chain fatty acids with long-chain alcohols. As one might expect, they form pliable solids at room temperature (what we generally think of as wax). Biologically, they function as protection for both plants and animals. In plants, waxes are secreted as a surface coating to prevent excessive evaporation and to protect against parasites. In animals, waxes are secreted to prevent dehydration, as a water-repellant to keep skin and feathers dry, and as a lubricant. For example, carnauba wax is made from the leaves of the Copernicia prunifera palm and is used to coat candies and wax cars. Bees secrete waxes to construct shelter, as shown in Figure 5.4.

Figure 5.4. Honeycomb Structure Made from Beeswax The solid and plastic nature of waxes, which contain esters with long alkyl chains, permits their use for structure building.

MCAT Concept Check 5.1:

Before you move on, assess your understanding of the material with these questions.

1.    Which components of membrane lipids contribute to their structural role in membranes? Which components contribute to function?

·        Structure:


·        Function:


2.    What is the difference between a sphingolipid that is also a phospholipid and one that is NOT?

3.    Name the three main types of sphingolipids and their characteristics.

Type

Phospholipid or Glycolipid?

Functional Group(s)

     
     
     

4.    What would happen if an amphipathic molecule were placed in a nonpolar solvent rather than an aqueous solution?