5. Lipid Structure and Function

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. 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.

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 globosides. Cerebrosides 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

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.

A surfactant lowers the surface tension at the surface of a liquid, serving as a detergent or emulsifier. This is important to how soap works. If we try to combine an aqueous solution and oil, as with vinegar and olive oil in salad dressing, these solutions will remain in separate phases.

If we were to add a soap, however, the two phases would appear to combine into a single phase, forming a colloid. This occurs because of the formation of micelles: tiny aggregates of soap with the hydrophobic tails turned inward and the hydrophilic heads turned outward, thereby shielding the hydrophobic lipid tails and allowing for overall solvation.

Prostaglandins acquired their name because they were first thought to be produced by the prostate gland, but have since been determined to be produced by almost all cells in the body. These 20- carbon molecules are unsaturated carboxylic acids derived from arachidonic acid and contain one five-carbon ring. They act as paracrine or autocrine hormones.

In many tissues, the biological function of prostaglandins is to regulate the synthesis of cyclic adenosine monophosphate (cAMP), which is a ubiquitous intracellular messenger. In turn, cAMP mediates the actions of many other hormones. Downstream effects of prostaglandins include powerful effects on smooth muscle function, influence over the sleep-wake cycle, and the elevation of body temperature associated with fever and pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin inhibit the enzyme cyclooxygenase (COX), which aids in the production of prostaglandins

Triacylglycerol deposits can be observed in cells as oily droplets in the cytosol. These serve as depots of metabolic fuel that can be recruited when the cell needs additional energy to divide or survive when other fuel supplies are low. Special cells in animals, known as adipocytes, store large amounts of fat and are found primarily under the skin, around mammary glands, and in the abdominal cavity.

In plants, triacylglycerol deposits are also found in seeds as oils. Triacylglycerols travel bidirectionally in the bloodstream between the liver and adipose tissue. The physical characteristics of triacylglycerols are primarily determined by the saturation (or unsaturation) of the fatty acid chains that make them up, much like phospholipids.

Cholesterol is a steroid of primary importance. Cholesterol is a major component of the phospholipid bilayer, and is responsible for mediating membrane fluidity. Cholesterol, like a phospholipid, is an amphipathic molecule containing both hydrophilic and hydrophobic components.

Interactions with both the hydrophobic tails and hydrophilic heads of phospholipids, allows cholesterol to maintain relatively constant fluidity in cell membranes. At low temperatures, it keeps the cell membrane from solidifying; at high temperatures, it holds the membrane intact and prevents it from becoming too permeable. Cholesterol also serves as a precursor to many important molecules, including steroid hormones, bile acids, and vitamin D.

KEY CONCEPT 1

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.

vitamin is an essential nutrient that cannot be adequately synthesized by the body and therefore must be consumed in the diet. Vitamins are commonly divided into water-soluble and lipid-soluble categories.

Lipid-soluble vitamins can accumulate in stored fat, whereas excess water-soluble vitamins are excreted through the urine. The fat-soluble vitamins include A, D, E, and K. Each of these has important and varied functions.

Nonpolar compounds can dissolve in the hydrophobic interior of the water-soluble micelle, meaning that our cleaning agents can dissolve both water-soluble and water-insoluble messes and then wash them all away together.

Micelles are also important in the body for the absorption of fat-soluble vitamins (A, D, E, and K) and complicated lipids such as lecithins. Fatty acids and bile salts secreted by the gallbladder form micelles that can deliver the fatty acids, vitamins, and cholesterol to the cells of the small intestine.

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,

Terpenoids, also sometimes referred to as isoprenoids, are derivatives of terpenes that have undergone oxygenation or rearrangement of the carbon skeleton. These compounds are further modified, as are terpenes, by the addition of an extensive variety of functional groups. Terpenoids share similar characteristics with terpenes in terms of both biological precursor function and aromatic properties, contributing to steroid eucalyptus, camphor, turmeric, and numerous other compounds.

Terpenoids are named in an analogous fashion, with diterpenoids deriving from four isoprene units and so on. Terpenes and terpenoids are precursor molecules that feed into various biosynthesis pathways that produce important products, including steroids, which have widespread effects on biological function, and vitamin A, which is vital to sight.

Saponification is the ester hydrolysis of triacylglycerols using a strong base. Traditionally, the base that is used is lye, the common name for sodium or potassium hydroxide.

The result is the basic cleavage of the fatty acid, leaving the sodium salt of the fatty acid and glycerol. The fatty acid salt is what we know as soap.

Terpenes are a class of lipids built from isoprene (C5H8) moieties and share a common structural pattern with carbons grouped in multiples of five. Terpenes are produced mainly by plants and also by some insects. They are generally strongly scented. In some cases, these pungent chemicals are part of the plant or insect's protective mechanism.

The strong smell of turpentine, a derivative of resin, comes from the monoterpenes that are resin's major components; terpenes actually get their name from their original discovery in turpentine. Terpenes are also the primary components of much more pleasant-smelling essential oils extracted from plants.

Terpenes are grouped according to the number of isoprene units present; a single terpene unit contains two isoprene units. Monoterpenes (C H ), which are abundant in both essential oils and turpentine as described above, contain two isoprene units. Sesquiterpenes (sesqui- meaning one-and-a-half) contain three isoprene units, and diterpenes contain four.

Vitamin A, which will be discussed later in this chapter, is a diterpene from which retinal, a visual pigment vital for sight, is derived. Triterpenes, with six isoprene units, can be converted to cholesterol and various steroids, also discussed later in this chapter. Carotenoids, like β-carotene and lutein, are tetraterpenes and have eight isoprene units. Natural rubber has isoprene chains between 1000 and 5000 units long and is therefore considered a polyterpene.

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.

Triacylglycerols, also called triglycerides,

are composed of three fatty acids bound by ester linkages to glycerol, For most naturally occurring triacylglycerols, it is rare for all three fatty acids to be the same. Overall, these compounds are nonpolar and hydrophobic. This contributes to their insolubility in water, as the polar hydroxyl groups of the glycerol component and the polar carboxylates of fatty acids are bound together, decreasing their polarity.

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.

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.

steroids

are metabolic derivatives of terpenes and are very different from the lipids mentioned earlier in this chapter in both structure and function. Steroids are characterized by having four cycloalkane rings fused together: three cyclohexane and one cyclopentane. Steroid functionality is determined by the oxidation status of these rings, as well as the functional groups they carry. It is important to note that the large number of carbons and hydrogens make steroids nonpolar, like the other lipids mentioned.

Steroid hormones

are steroids that act as hormones, meaning that they are secreted by endocrine glands into the bloodstream and then travel on protein carriers to distant sites, where they can bind to specific high-affinity receptors and alter gene expression levels. Steroid hormones are potent biological signals that regulate gene expression and metabolism, affecting a wide variety of biological systems even at low concentrations.

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.

Vitamin D, or cholecalciferol,

can be consumed or formed in a UV-driven reaction in the skin. In the liver and kidneys, vitamin D is converted to calcitriol (1,25-(OH) D ), the biologically active form of vitamin D. Calcitriol increases calcium and phosphate uptake in the intestines, which promotes bone production. A lack of vitamin D can result in rickets, a condition seen in children and characterized by underdeveloped, curved long bones as well as impeded growth.

Vitamin E

characterizes a group of closely related lipids called tocopherols and tocotrienols. These are characterized by a substituted aromatic ring with a long isoprenoid side chain and are characteristically hydrophobic. Tocopherols are biological antioxidants. The aromatic ring reacts with free radicals, destroying them. This, in turn, prevents oxidative damage, an important contributor to the development of cancer and aging.

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.

Vitamin K

is actually a group of compounds, including phylloquinone (K ) and the menaquinones (K ). Vitamin K is vital to the posttranslational modifications required to form prothrombin, an important clotting factor in the blood. The aromatic ring of vitamin K undergoes a cycle of oxidation and reduction during the formation of prothrombin. Vitamin K is also required to introduce calciumbinding sites on several calcium-dependent proteins.

Vitamin A, or carotene,

is an unsaturated hydrocarbon that is important in vision, growth and development, and immune function. The most significant metabolite of vitamin A is the aldehyde form, retinal, which is a component of the light-sensing molecular system in the human eye. Retinol, the storage form of vitamin A, is also oxidized to retinoic acid, a hormone that regulates gene expression during epithelial development.

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.