What are lipids? |

Structure and Functions

Lipids are a class of bio-organic compounds that are typically insoluble in water and relatively soluble in organic solvents such as alcohols, ethers, and hydrocarbons. Unlike the other classes of organic molecules found in biological systems (carbohydrates, proteins, and nucleic acids), lipids possess a unifying physical property—solubility behavior—rather than a unifying structural feature. Fats, oils, some vitamins and hormones, and most of the nonprotein components of cell membranes are lipids.

There are two categories of lipids—those that undergo saponification and those that are nonsaponifiable. The saponifiable lipids can be divided into simple and complex lipids. Simple lipids, which are composed of carbon, hydrogen, and oxygen, yield fatty acids and an alcohol upon saponification. Complex lipids contain one or more additional elements, such as phosphorus, nitrogen, and sulfur, yielding fatty acids, alcohol, and other compounds on saponification.

The fatty acid building blocks of saponifiable lipids may be either saturated, which means that as many hydrogen atoms as possible are attached to the carbon chain, or unsaturated, which means that at least two hydrogen atoms are missing. Saturated fatty acids are white solids at room temperature, while unsaturated ones are liquids at room temperature, because of a geometrical difference in the long carbon chains. The carbon atoms of a saturated fatty acid are arranged in a zigzag or accordion configuration. These chains are stacked on top of one another in a very orderly and efficient fashion, making it difficult to separate the chains from one another. When carbons in the chain are missing hydrogen atoms, the regular zigzag of the chain is disrupted, leading to less efficient packing, which allows the chains to be separated more easily. Saturated fatty acids have a higher melting temperature because they require more energy to separate their chains than do unsaturated fatty acids. Unsaturated fatty acids can be converted into saturated ones by adding hydrogen atoms through a process called hydrogenation.

Simple lipids can be divided into triglycerides and waxes. Waxes such as beeswax, lanolin (from lamb’s wool), and carnauba wax (from a palm tree) are esters formed from an alcohol with a long carbon chain and a fatty acid. These compounds, which are solids at room temperature, serve as protective coatings. Most plant leaves are coated with a wax film to prevent attack by microorganisms and loss of water through evaporation. Animal fur and bird feathers have a wax coating. For example, the wax coating on their feathers is what allows ducks to stay afloat.

Edible fats and oils such as lard (pig fat), tallow (beef fat), corn oil, and butter are triglycerides. Triglyceride molecules are fatty acid esters in which three fatty acids (all saturated, all unsaturated, or mixed) combine with one molecule of the alcohol glycerol. Oils are triglycerides that are liquid at room temperature, while fats are solid at room temperature. The fluidity of a triglyceride is dependent on the nature of its fatty acid chains; the more unsaturated the triglyceride, the more fluid its structure. The triglycerides found in animals tend to have more saturated fatty acids than do those found in plants. Vegetable oils and fish oils are frequently polyunsaturated.

Complex lipids are classified as phospholipids or glycolipids. Structurally, phospholipids are composed of fatty acids and a phosphate group. Glycerol-based lipids called phosphoglycerides contain glycerol, two fatty acids, and a phosphate group. The phosphoglyceride structure contains a hydrophilic (polar) head, the phosphate unit, and two hydrophobic (nonpolar) fatty acid tails. The polar head can interact strongly with water, while the nonpolar tails interact strongly with organic solvents and avoid water. Egg yolks contain a large amount of the phosphoglyceride phosphatidylcholine (also called lecithin). This lipid is used to form the emulsion mayonnaise from oil and vinegar. Normally, oil and water do not mix. The hydrophobic oil forms a separate layer on top of the water. Since lecithin’s structure contains both a hydrophobic and a hydrophilic region, it can attach to the water with its polar head and the oil with its nonpolar tail, preventing the two materials from separating. Lipids derived from the alcohol sphingosine are called sphingolipids. They contain one fatty acid, one long hydrocarbon chain and a phosphate group. Like the phosphoglycerides, sphingolipids have a head-and-two-tail structure. Sphingolipids are important components in the protective and insulating coating that surrounds nerves.

Glycolipids differ from phospholipids in that they possess a sugar group in place of the phosphate group. Their structure is again the polar head and dual tail arrangement in which the sugar is the hydrophilic unit. Cerebrosides, which are sphingosine-based glycolipids containing a simple sugar such as galactose or glucose, are found in large amounts in the white matter of the brain and in the myelin sheath. Gangliosides, which are found in the gray matter of the brain, in neural tissue, and in the receptor sites for neurotransmitters, contain a more complex sugar component.

Nonsaponifiable lipids do not contain esters of fatty acids as their basic structural feature. Steroids are an important class of nonsaponifiable lipids. All steroids possess an identical four-ring framework called the steroid nucleus, but they differ in the groups that are attached to their ring systems. Examples of steroids are sterols such as cholesterol, the bile acids secreted by the liver, the sex hormones, corticosteroids secreted by the adrenal cortex, and digitoxin from the digitalis plant, which is used to treat heart disease.

Lipids constitute about 50 percent of the mass of most animal cell membranes. Biological membranes control the chemical environment of the space they enclose. They are selective filters controlling what substances enter and exit the cell, since they constitute a relatively impermeable barrier against most water-soluble molecules. The three types of lipids involved are phospholipids (most abundant), glycolipids, and cholesterol. Phospholipids, when surrounded by an aqueous environment, tend to organize into a double layer of lipid molecules, a bilayer, allowing their hydrophobic tails to be buried internally and their hydrophilic heads to be exposed to the water. These phospholipids have one saturated and one unsaturated tail. Differences in tail length and saturation influence the packing efficiency of the molecules and affect the fluidity of the membrane. Short, unsaturated tails increase the fluidity of the membrane. Cholesterol is important in maintaining the mechanical stability of the lipid bilayer, thereby preventing a change from the fluid state to a rigid crystalline state. It also decreases the permeability of small water-soluble molecules.

The lipid bilayer provides the basic structure of the membrane and serves as a two-dimensional solvent for protein molecules. Protein molecules are responsible for most membrane functions; for example, they can provide receptor sites, catalyze reactions, or transport molecules across the membrane. These proteins may extend across the bilayer (transmembrane proteins) or be associated with only one face of the bilayer. Cell membranes also have carbohydrates attached to the outer face of the bilayer. These carbohydrates are bound to membrane proteins or part of a glycolipid. Typically, 2 to 10 percent of a membrane’s total weight is carbohydrate. Evidence exists that cell-surface carbohydrates are used as recognition sites for chemical processes.

Lipids play an important role in health and well-being. The body acquires lipids directly from dietary lipids and indirectly by converting other nutrients into lipids. There are two fatty acids, linoleic and linolenic acids, which are called essential fatty acids. Since these fatty acids cannot be synthesized in the body in sufficient amounts, their supply must come directly from dietary sources. Fortunately, these acids are widely found in foodstuffs, so deficiency is rarely observed in adults.

About 95 percent of the lipids in foods are triglycerides, which provide 30 to 50 percent of the calories in an average diet. Triglycerides produce 4,000 calories of energy per pound, compared to the 1,800 calories per pound produced by carbohydrates or proteins. Since the triglyceride is such an efficient energy source, the body converts carbohydrates and proteins into adipose (reserve fatty) tissue for storage to be used when extra fuel is required.

While carbohydrates and proteins undergo major degradation in the stomach, triglycerides remain intact, forming large globules that float to the top of the mixture. Fats spend a longer time than other nutrients in the stomach, slowing molecular activity before continuing into the intestines. Thus, a fat-laden meal gives longer satiety than a low-fat one.

In the small intestine, bile salts split fat globules into smaller droplets, allowing enzymes called lipases to saponify the triglycerides. In some instances, the fatty acids at the two ends are removed, leaving one attached as a monoglyceride. About 97 percent of dietary triglycerides are absorbed into the bloodstream; the remainder are excreted. Although glycerol and fatty acids with short carbon chains are water-soluble enough to dissolve in the blood, the long-chain fatty acids and monoglycerides are not. These insoluble materials recombine to form new triglycerides. Since these hydrophobic triglycerides would form large globules if they were dumped directly into the blood, small triglyceride droplets are surrounded with a protective protein coat that can dissolve in water, taking the encapsulated triglyceride with it. This structure is an example of a lipoprotein.

Cholesterol is found in relatively small (milligram) quantities in foods, compared to triglycerides. Cholesterol supplies raw materials for the production of bile salts and to be used as a structural constituent of brain and nerve tissue. Since these functions are important to animals but serve no purpose in plants, cholesterol is found only in animals. Only about 50 percent of dietary cholesterol is absorbed into the blood; the rest is excreted. Much of the body’s supply of cholesterol is produced in the liver. For most individuals, the amount of cholesterol synthesized in the body is larger than the amount absorbed directly from the diet.

Digested lipids released from the intestine and those synthesized in the liver compose the lipid content of the blood. The fatty acids required by the liver are obtained directly from the bloodstream or by synthesis from sources such as glucose, amino acids, and alcohol. Liver-synthesized triglycerides are incorporated into lipoprotein packages before entering the bloodstream. There are three types of lipoprotein packages that transport lipids to and from the liver. Very-low-density lipoproteins (VLDLs) transport triglycerides to tissues;
low-density lipoproteins (LDLs) transport the cholesterol from the liver to other cells; and high-density lipoproteins (HDLs) transport cholesterol from other tissues to the liver for destruction.

Disorders and Diseases

Lipid consumption is an important dietary concern. Lipid deficiency is rarely observed in adults but can occur in infants who are fed nonfat formulas. Since fatty acids are essential for growth, lipid consumption should not be restricted in individuals under two years of age. Excess lipid consumption is associated with health problems such as obesity and cardiovascular disease. Although excess calories from any dietary source can lead to obesity, the body must expend less energy to store dietary fat than to store dietary carbohydrate as body fat. Thus, high-fat diets produce more body fat than do high-carbohydrate, low-fat diets.

Atherosclerosis, or “hardening of the arteries,” is the leading cause of cardiovascular disease. A strong correlation exists between diets high in saturated fats and the incidence of atherosclerosis. In this condition, deposits called plaques, which have a high cholesterol content, form on artery walls. Over time, these deposits narrow the artery and decrease its elasticity, resulting in reduced blood flow. Blockages can occur, resulting in heart attack or stroke. High serum cholesterol levels (total blood cholesterol content) often result in increased plaque formation. Since dietary cholesterol is not efficiently absorbed into the bloodstream and the serum cholesterol level is largely determined by the amount of cholesterol synthesized in the liver, high serum cholesterol levels are frequently related to high saturated fat intake.

Since the measurement of the serum cholesterol level gives the total cholesterol concentration of the blood, it can be a somewhat misleading predictor of atherosclerosis risk; cholesterol is not free in blood, but is encapsulated in lipoproteins. Since the cholesterol packaged in the LDL, cholesterol that can be deposited in plaques (“bad” cholesterol), has a very different fate from that in the HDL, which is transporting cholesterol for destruction (“good” cholesterol), measuring the ratio of LDL cholesterol to HDL cholesterol has been found to be a better indicator of atherosclerosis risk. Decreasing dietary intake of cholesterol and saturated fats, increasing water-soluble fibers in the diet, removing excess body weight, and increasing the amount of aerobic exercise will all serve to improve the LDL-C/HDL-C ratio.

A number of hereditary diseases are known that result from abnormal accumulation of the complex lipids utilized in membranes. These diseases are called lipid (or lysosomal) storage diseases, or lipidoses. In normal individuals, the amount of each complex lipid present in the body is relatively constant; in other words, the rate of formation equals the rate of destruction. The lipids are broken down by enzymes that attack specific bonds in the lipid structure. Lipid storage diseases occur when a lipid-degrading enzyme is defective or absent. In these cases, the lipid synthesis proceeds normally, but the degradation is impaired, causing the lipid or a partial degradation product to accumulate, with consequences such as an enlarged liver and spleen, mental disability, blindness, and death.

Niemann-Pick, Gaucher’s, and Tay-Sachs diseases are examples of lipidoses. Niemann-Pick disease is caused by a defect in an enzyme that breaks down sphingomyelin. The disease becomes apparent in infancy, causing mental retardation and death normally by age four. Gaucher’s disease, a more common disease involving the accumulation of a glycolipid, produces two different syndromes. The acute cerebral form affects infants, causing severe nervous system abnormalities, retardation, and death before age one. The chronic form, which may become evident at any age, causes enlargement of the spleen, anemia, and erosion of the bones. In Tay-Sachs disease, a partially degraded lipid accumulates in the tissues of the central nervous system. Symptoms include progressive loss of vision, paralysis, and death at three or four years of age. Although Tay-Sachs disease is relatively rare (1 in 300,000
births), it has a high incidence in individuals of Eastern European Jewish descent (1 in 3,600 births). This defect is a recessive genetic trait that is found in one of every twenty-eight members of this population. For two parents who are both carriers of this trait, there is a one in four chance that their child will develop Tay-Sachs disease. Tests have been developed to detect the presence of the defective gene in the parent, and the amniotic fluid of a developing fetus can be sampled using a technique called amniocentesis to detect Tay-Sachs disease. Lipid storage diseases have no known cures; however, they can be prevented through genetic counseling.

Perspective and Prospects

The ability of a cell to discriminate in its chemical exchanges with the environment is fundamental to life. How the cell membrane accomplishes this feat has been a subject of intense biochemical research since the beginning of the twentieth century.

In 1895, Ernst Overton observed that substances that are lipid-soluble enter cells more quickly than those that are lipid-insoluble. He reasoned that the membrane must be composed of lipids. About twenty years later, chemical analysis showed that membranes also contain proteins. Irwin Langmuir prepared the first artificial membrane in 1917 by mixing a phospholipid-containing hydrocarbon solution with water. Evaporation of the hydrocarbon left a phospholipid film on the surface of the water, which showed that only the hydrophilic heads contacted the water. When the Dutch biologists E. Gorter and F. Grendel deposited the lipids from red blood cell membranes on a water surface and decreased the occupied surface area with a movable barrier, a continuous film resulted that occupied an area approximately twice the surface area of the original red blood cells. In 1935, all these observations, along with the fact that the surfaces of artificial membranes containing only phospholipids are less water-absorbent than the surfaces of true biological membranes, were combined by Hugh Davson and James Danielli into a membrane model in which a phospholipid bilayer was sandwiched between two water-absorbent protein layers.

The technological advances of the 1950s in x-ray diffraction and electron
microscopy allowed the structures of membranes to be probed directly. Such studies revealed that membranes are indeed composed of parallel orderly arrays of lipids, although many of the proteins are attached to one of the faces of the bilayer: The Davson-Danielli model was too simplistic. The freeze-fracture technique of preparing cells for electron microscopy has provided the most information about the nature of membrane proteins. In this technique, the two layers are separated so that the inner topography can be studied. Instead of the smooth surface predicted by the Davson-Danielli model, a cobblestone-like surface was observed that resulted from proteins penetrating into the interior of the membrane. All experimental evidence supports the fluid mosaic model for biological membranes, a model first proposed by Seymour Singer and Garth Nicholson in 1972. In this model, proteins are dispersed and embedded in a phospholipid bilayer that is in a fluid state. How membranes function was the next question to be considered.

Although most of the small molecules needed by cells cross the barrier via protein channels, some essential nutrients, such as cholesterol in its LDL package, are too large to pass through a small channel. In 1986, Michael Brown and Joseph Goldstein received the Nobel Prize for their discovery of specific protein receptors on the membranes of liver cells to which LDL molecules attach. These receptors move across the surface until they encounter a shallow indentation or pit. As the pit deepens, the membrane closes behind the LDL, forming a coating allowing transport across the hydrophobic membrane interior. The presence of insufficient numbers of these receptors causes abnormal LDL-cholesterol buildup in the blood.

Many questions remain unanswered concerning the roles of proteins and glycolipids in membranes. Membranes are involved in the movement, growth, and development of cells. How the membrane is involved in the uncontrolled multiplication and migration in cancer is one medically important question. Experiments that will answer questions about how membrane structure affects functioning should lead to the development of new medical treatments.

Bibliography

Bettelheim, Frederick A., et al. Introduction to General, Organic, and Biochemistry. 10th ed. Belmont, Calif: Brooks/Cole Cengage Learning, 2013.

Bloomfield, Molly M., and Lawrence J. Stephens. Chemistry and the Living Organism. 6th ed. New York: John Wiley, 1996.

Brown, Michael S., and Joseph L. Goldstein. “How LDL Receptors Influence Cholesterol and Atherosclerosis.” Scientific American 251 (November, 1984): 58–66.

Carlson, Emily. "The Big, Fat World of Lipids." NIH National Institute of General Medical Sciences: Inside Life Science, August 9, 2012.

Christian, Janet L., and Janet L. Greger. Nutrition for Living. 4th ed. Redwood City, Calif.: Benjamin/Cummings, 1994.

Cornatzer, W. E. Role of Nutrition in Health and Disease. Springfield, Ill.: Thomas, 1989.

MedlinePlus. "Dietary Fats." MedlinePlus, June 28, 2013.

National Institute of General Medical Sciences. "You Are What You Eat." NIH National Institute of General Medical Sciences: ChemHealthWeb, August 9, 2012.

Sikorski, Zdzisław E., and Anna Kołakowska, eds. Chemical and Functional Properties of Food Lipids. Boca Raton, Fla.: CRC Press, 2002.

Vance, Dennis E., and Jean E. Vance, eds. Biochemistry of Lipids, Lipoproteins, and Membranes. 5th ed. Boston: Elsevier, 2008.