Campbell Biology Chapter 5
.pdf
School
Polytechnic University of Puerto Rico**We aren't endorsed by this school
Course
BME 1010
Subject
Chemistry
Date
Dec 16, 2024
Pages
26
Uploaded by vigvaller
5The Structure and Function of Large Biological Molecules ▲Figure 5.1 Why is the structure of a protein important for its function?The Molecules of LifeGiven the rich complexity of life on Earth, it might surprise you that the most important large molecules found in all living things—from bacteria to elephants—can be sorted into just four main classes: carbohydrates, lipids, proteins, and nucleic acids. On the molecular scale, members of three of these classes—carbohydrates, proteins, and nucleic acids—are huge and are there-fore called macromolecules. For example, a protein may consist of thousands of atoms that form a molecular colossus with a mass well over 100,000 daltons. Considering the size and complexity of macromolecules, it is noteworthy that biochemists have determined the detailed structure of so many of them. The image in Figure 5.1is a molecular model of a protein called alcohol dehydroge-nase, which breaks down alcohol in the body. The architecture of a large biological molecule plays an essential role in its func-tion. Like water and simple organic molecules, large biological molecules exhibit unique emergent properties arising from the orderly arrangement of their atoms. In this chapter, we’ll first consider how macromolecules are built. Then we’ll examine the structure and function of all four classes of large biological molecules: carbohy-drates, lipids, proteins, and nucleic acids.66K E Y C O N C E P T S5.1 Macromolecules are polymers, built from monomers5.2 Carbohydrates serve as fuel and building material5.3 Lipids are a diverse group of hydrophobic molecules5.4 Proteins include a diversity of structures, resulting in a wide range of functions5.5 Nucleic acids store, transmit, and help express hereditary information5.6 Genomics and proteomics have transformed biological inquiry and applications
differences between close relatives such as human siblings reflect small variations in polymers, particularly DNA and proteins. Molecular differences between unrelated individu-als are more extensive, and those between species greater still. The diversity of macromolecules in the living world is vast, and the possible variety is effectively limitless.What is the basis for such diversity in life’s polymers? These molecules are constructed from only 40 to 50 com-mon monomers and some others that occur rarely. Building a huge variety of polymers from such a limited number of monomers is analogous to constructing hundreds of thou-sands of words from only 26 letters of the alphabet. The key is arrangement—the particular linear sequence that the units follow. However, this analogy falls far short of describ-ing the great diversity of macromolecules because most biological polymers have many more monomers than the number of letters a word, even the longest ones. Proteins, for example, are built from 20 kinds of amino acids arranged in chains that are typically hundreds of amino acids long. The molecular logic of life is simple but elegant: Small mol-ecules common to all organisms are ordered into unique macromolecules.Despite this immense diversity, molecular structure and function can still be grouped roughly by class. Let’s examine each of the four major classes of large biological molecules. For each class, the large molecules have emergent properties not found in their individual building blocks.C O N C E P T 5.1Macromolecules are polymers, built from monomersThe macromolecules in three of the four classes of life’s organic compounds—carbohydrates, proteins, and nucleic acids, all except lipids—are chain-like molecules called polymers (from the Greek polys, many, and meros, part). A polymeris a long molecule consisting of many similar or identical building blocks linked by covalent bonds, much as a train consists of a chain of cars. The repeating units that serve as the building blocks of a polymer are smaller mol-ecules called monomers(from the Greek monos, single). Some monomers also have other functions of their own.The Synthesis and Breakdown of PolymersAlthough each class of polymer is made up of a different type of monomer, the chemical mechanisms by which cells make and break down polymers are basically the same in all cases. In cells, these processes are facilitated by enzymes, special-ized macromolecules that speed up chemical reactions. Monomers are connected by a reaction in which two mol-ecules are covalently bonded to each other, with the loss of a water molecule; this is known as a dehydration reaction(Figure 5.2a). When a bond forms between two monomers, each monomer contributes part of the water molecule that is released during the reaction: One monomer provides a hydroxyl group (¬OH), while the other provides a hydrogen (¬H). This reaction is repeated as monomers are added to the chain one by one, making a polymer. Polymers are disassembled to monomers by hydrolysis, a process that is essentially the reverse of the dehydration reaction (Figure 5.2b). Hydrolysis means water breakage (from the Greek hydro, water, and lysis, break). The bond between monomers is broken by the addition of a water molecule, with a hydrogen from water attaching to one monomer and the hydroxyl group attaching to the other. An example of hydrolysis within our bodies is the process of digestion. The bulk of the organic material in our food is in the form of polymers that are much too large to enter our cells. Within the digestive tract, various enzymes attack the polymers, speeding up hydrolysis. Released monomers are then absorbed into the bloodstream for distribution to all body cells. Those cells can then use dehydration reactions to assemble the monomers into new, different polymers that can perform specific functions required by the cell.The Diversity of PolymersA cell has thousands of different macromolecules; the col-lection varies from one type of cell to another. The inherited HHO HShort polymerDehydration removes a water molecule, forming a new bond.Hydrolysis adds a water molecule, breaking a bond.Longer polymerUnlinked monomerHOH2OH2O1234HO H1234HOHHOH123HOH123(a) Dehydration reaction: synthesizing a polymer(b) Hydrolysis: breaking down a polymer▼Figure 5.2 The synthesis and breakdown of polymers.CHAPTER 5The Structure and Function of Large Biological Molecules 67
68UNIT ONEThe Chemistry of LifeC O N C E P T C H E C K 5 . 11. What are the four main classes of large biological mol-ecules? Which class does not consist of polymers?2. How many molecules of water are needed to completely hydrolyze a polymer that is ten monomers long?3. W H AT I F ?If you eat a piece of fish, what reactions must occur for the amino acid monomers in the protein of the fish to be converted to new proteins in your body?For suggested answers, see Appendix A.C O N C E P T 5.2Carbohydrates serve as fuel and building materialCarbohydratesinclude sugars and polymers of sugars. The simplest carbohydrates are the monosaccharides, or simple sugars; these are the monomers from which more complex carbohydrates are built. Disaccharides are double sugars, consisting of two monosaccharides joined by a covalent bond. Carbohydrate macromolecules are polymers called polysaccharides, composed of many sugar building blocks.SugarsMonosaccharides(from the Greek monos, single, and sac-char, sugar) generally have molecular formulas that are some multiple of the unit CH2O. Glucose (C6H12O6), the most common monosaccharide, is of central importance in the chemistry of life. In the structure of glucose, we can see the trademarks of a sugar: The molecule has a carbonyl group (CO) and multiple hydroxyl groups (¬OH) (Figure 5.3). Depending on the location of the carbonyl group, a sugar is either an aldose (aldehyde sugar) or a ketose (ketone sugar). Glucose, for example, is an aldose; fructose, an isomer of glucose, is a ketose. (Most names for sugars end in -ose.) An-other criterion for classifying sugars is the size of the carbon skeleton, which ranges from three to seven carbons long. Glucose, fructose, and other sugars that have six carbons are called hexoses. Trioses (three-carbon sugars) and pentoses (five-carbon sugars) are also common. Still another source of diversity for simple sugars is in the spatial arrangement of their parts around asymmetric carbons. (Recall that an asymmetric carbon is a carbon at-tached to four different atoms or groups of atoms.) Glucose and galactose, for example, differ only in the placement of parts around one asymmetric carbon (see the purple boxes in Figure 5.3). What seems like a small difference is signifi-cant enough to give the two sugars distinctive shapes and binding activities, thus different behaviors.Although it is convenient to draw glucose with a linear car-bon skeleton, this representation is not completely accurate. CHOHCOHHCHOHCHOHHCOHCHOHCHOHCOHHCHOHCHOHCHOHCHOHHCHOHCHOHCHOHHCOCHOHHCHOHCHOHCHOHHCOCHOHCOHCHOHCHOHGlyceraldehydeAn initial breakdownproduct of glucoseDihydroxyacetoneAn initial breakdownproduct of glucoseRibuloseAn intermediatein photosynthesisRiboseA component of RNAGlucoseGalactoseFructoseAn energy source for organismsEnergy sources for organismsCHOHCOHHCHOHCHOHHHOHHOHHOHCHOHCHOHCCCTrioses: 3-carbon sugars (C3H6O3)Pentoses: 5-carbon sugars (C5H10O5)Hexoses: 6-carbon sugars (C6H12O6)Aldoses (Aldehyde Sugars)Carbonyl group at end of carbon skeletonKetoses (Ketone Sugars)Carbonyl group withincarbon skeleton▲Figure 5.3 The structure and classification of some mono-saccharides.Sugars vary in the location of their carbonyl groups (orange), the length of their carbon skeletons, and the spatial arrange-ment around asymmetric carbons (compare, for example, the purple portions of glucose and galactose).M A K E C O N N E C T I O N SIn the 1970s, a process was developed that converts the glucose in corn syrup to its sweeter-tasting isomer, fructose. High-fructose corn syrup, a common ingredient in soft drinks and pro-cessed food, is a mixture of glucose and fructose. What type of isomers are glucose and fructose? (See Figure 4.7.)
CHAPTER 5The Structure and Function of Large Biological Molecules 69In aqueous solutions, glucose molecules, as well as most other five- and six-carbon sugars, form rings (Figure 5.4). Monosaccharides, particularly glucose, are major nutri-ents for cells. In the process known as cellular respiration, cells extract energy from glucose molecules by breaking them down in a series of reactions. Not only are simple-sugar molecules a major fuel for cellular work, but their car-bon skeletons also serve as raw material for the synthesis of other types of small organic molecules, such as amino acids and fatty acids. Sugar molecules that are not immediately used in these ways are generally incorporated as monomers into disaccharides or polysaccharides.A disaccharideconsists of two monosaccharides joined by a glycosidic linkage, a covalent bond formed between two monosaccharides by a dehydration reaction. For example, maltose is a disaccharide formed by the linking of two mol-ecules of glucose (Figure 5.5a). Also known as malt sugar, maltose is an ingredient used in brewing beer. The most prevalent disaccharide is sucrose, which is table sugar. Its two monomers are glucose and fructose (Figure 5.5b). Plants gen-erally transport carbohydrates from leaves to roots and other nonphotosynthetic organs in the form of sucrose. Lactose, the sugar present in milk, is another disaccharide, in this case a glucose molecule joined to a galactose molecule. HOHCOHHHOHHOHHOHHOHH(a) (b)2C3C4C4C5C6C1HOHOHH3 CCOHH4CHOH1HHOOHOHH2C2C3 COHH1H5C5C6 CH2OH6 CH2OHCHOHOHHOHCH2OHOHHHHOOH321564OLinear and ring forms. Chemical equilibrium between the linear and ring structures greatly favors the formation of rings. The carbons of the sugar are numbered 1 to 6, as shown. To form the glucose ring, carbon 1 (magenta) bonds to the oxygen (blue) attached to carbon 5.Abbreviated ring structure. Each unlabeled corner represents a carbon. The ring’s thicker edge indicates that you are looking at the ring edge-on; the components attached to the ring lie above or below the plane of the ring.▲Figure 5.4 Linear and ring forms of glucose.D R AW I TStart with the linear form of fructose (see Figure 5.3) and draw the formation of the fructose ring in two steps. First, number the carbons starting at the top of the linear structure. Then draw the molecule in the same orientation as the glucose in the middle of (a) above, attaching carbon 5 via its oxygen to carbon 2. Compare the number of carbons in the fructose and glucose rings.OGlucoseGlucoseMaltose1HOOHOH4OH1– 4glycosidiclinkage(a)H2OHOHHOHCH2OHOHHHHOHOHHOHCH2OHOHHHHOHOHHOHCH2OHOHHHHOHHOHCH2OHOHHHOSucrose121– 2glycosidiclinkageHOHHOHCH2OHOHHHHOCH2OHHGlucoseFructoseHOOHH2OHOHHOHCH2OHOHHHHOOHHOCH2OHHHOCH2OHHOHHOCH2OHHHODehydration reaction in the synthesis of maltose. The bonding of two glucose units forms maltose. The 1–4 glycosidic linkage joins the number 1 carbon of one glucose to the number 4 carbon of the second glucose. Joining the glucose monomers in a different way would re- sult in a different disaccharide. (b) Dehydration reaction in the synthesis of sucrose. Sucrose is a disaccharide formed from glucose and fructose. Notice that fructose forms a five-sided ring, though it is a hexose like glucose.▲Figure 5.5 Examples of disaccharide synthesis.D R AW I TReferring to Figures 5.3 and 5.4, number the carbons in each sugar in this figure. Insert arrows linking the carbons to show how the numbering is consistent with the name of each glycosidic linkage.
70UNIT ONEThe Chemistry of LifePolysaccharidesPolysaccharidesare macromolecules, polymers with a few hundred to a few thousand monosaccharides joined by gly-cosidic linkages. Some polysaccharides serve as storage ma-terial, hydrolyzed as needed to provide sugar for cells. Other polysaccharides serve as building material for structures that protect the cell or the whole organism. The architecture and function of a polysaccharide are determined by its sugar monomers and by the positions of its glycosidic linkages.Storage PolysaccharidesBoth plants and animals store sugars for later use in the form of storage polysaccharides (Figure 5.6). Plants store starch, a polymer of glucose monomers, as granules within cellular structures known as plastids, which include chloroplasts. Synthesizing starch enables the plant to stock-pile surplus glucose. Because glucose is a major cellular fuel, starch represents stored energy. The sugar can later be with-drawn from this carbohydrate “bank” by hydrolysis, which breaks the bonds between the glucose monomers. Most animals, including humans, also have enzymes that can hy-drolyze plant starch, making glucose available as a nutrient for cells. Potato tubers and grains are the major sources of starch in the human diet. Most of the glucose monomers in starch are joined by 1–4 linkages (number 1 carbon to number 4 carbon), like the glucose units in maltose (see Figure 5.5a). The simplest form of starch, amylose, is unbranched. Amylopectin, a more complex starch, is a branched polymer with 1–6 link-ages at the branch points. Both of these starches are shown in Figure 5.6a.OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOGlycogen (branched)Storage structures (plastids) containing starch granules in a potato tuber cellGlucosemonomerAmylose (unbranched)Amylopectin(somewhat branched)Glycogengranules in muscletissue(a) Starch(b) Glycogen(c) CelluloseOOOOOOOOOHOHOOOOOOOOOOOOOOOCellulose molecule (unbranched)Cellulose microfibrils in a plant cell wallPlant cell,surroundedby cell wallMicrofibril (bundle ofabout 80 cellulose molecules)Hydrogen bonds betweenparallel cellulose moleculeshold them together.Cell wall10 uni03BCm0.5 uni03BCm1 uni03BCm50 uni03BCmOO▲Figure 5.6 Polysaccharides of plants and animals.(a)Starch stored in plant cells, (b)glycogen stored in muscle cells, and (c)structural cellulose fibers in plant cell walls are all polysaccharides composed entirely of glucose monomers (green hexagons). In starch and glycogen, the polymer chains tend to form helices in unbranched regions because of the angle of the linkages between glucose mol-ecules. There are two kinds of starch: amylose and amylopectin. Cellulose, with a different kind of glucose linkage, is always unbranched.
CHAPTER 5The Structure and Function of Large Biological Molecules 71Animals store a polysaccharide called glycogen, a poly-mer of glucose that is like amylopectin but more extensively branched (Figure 5.6b). Vertebrates store glycogen mainly in liver and muscle cells. Hydrolysis of glycogen in these cells releases glucose when the demand for sugar increases. This stored fuel cannot sustain an animal for long, however. In humans, for example, glycogen stores are depleted in about a day unless they are replenished by consumption of food. This is an issue of concern in low-carbohydrate diets, which can result in weakness and fatigue.Structural PolysaccharidesOrganisms build strong materials from structural polysac-charides. For example, the polysaccharide called celluloseis a major component of the tough walls that enclose plant cells (Figure 5.6c). On a global scale, plants produce almost 1014kg (100 billion tons) of cellulose per year; it is the most abundant organic compound on Earth. Like starch, cellulose is a polymer of glucose, but the gly-cosidic linkages in these two polymers differ. The difference is based on the fact that there are actually two slightly differ-ent ring structures for glucose (Figure 5.7a). When glucose forms a ring, the hydroxyl group attached to the number 1 carbon is positioned either below or above the plane of the ring. These two ring forms for glucose are called alpha (α) and beta (β), respectively. (Greek letters are often used as a “numbering” system for different versions of biological structures, much as we use the letters a, b, c, and so on for the parts of a question or a figure.) In starch, all the glucose monomers are in the α configuration (Figure 5.7b), the arrangement we saw in Figures 5.4 and 5.5. In contrast, the glucose monomers of cellulose are all in the βconfiguration, making every glucose monomer “upside down” with respect to its neighbors (Figure 5.7c;see also Figure 5.6c). The differing glycosidic linkages in starch and cellulose give the two molecules distinct three-dimensional shapes. Whereas certain starch molecules are largely helical, a cel-lulose molecule is straight. Cellulose is never branched, and some hydroxyl groups on its glucose monomers are free to hydrogen-bond with the hydroxyls of other cellulose mol-ecules lying parallel to it. In plant cell walls, parallel cellulose molecules held together in this way are grouped into units called microfibrils (see Figure 5.6c). These cable-like micro-fibrils are a strong building material for plants and an im-portant substance for humans because cellulose is the major constituent of paper and the only component of cotton.Enzymes that digest starch by hydrolyzing its α linkages are unable to hydrolyze the βlinkages of cellulose due to the different shapes of these two molecules. In fact, few organ-isms possess enzymes that can digest cellulose. Almost all animals, including humans, do not; the cellulose in our food passes through the digestive tract and is eliminated with the feces. Along the way, the cellulose abrades the wall of the digestive tract and stimulates the lining to secrete mucus, which aids in the smooth passage of food through the tract. Thus, although cellulose is not a nutrient for humans, it is an important part of a healthful diet. Most fruits, vegetables, and whole grains are rich in cellulose. On food packages, “insoluble fiber” refers mainly to cellulose.Some microorganisms can digest cellulose, break-ing it down into glucose monomers. A cow harbors CHOHCOHHCHOHCHOHCHOHCHOHβGlucoseαGlucose(a)OH1H4HOHCH2OHOHHHHOOH1H4HOHCH2OHOHHHHOO(b)1OCH2OHCH2OHCH2OHCH2OHHOOH4OOOOOOHOHOHOHOHOHOHCH2OHO1OHO4OOCH2OHCH2OHCH2OHOHOHOHOHOHOOOOHOHOHOHOHOHOHαand βglucose ring structures. These two interconvertible forms of glucose differ in the placement of the hydroxylgroup (highlighted in blue) attached to the number 1 carbon. Starch: 1–4 linkage ofαglucose monomers.All monomers are in the same orientation. Compare the positions of the OH groups highlighted in yellow with those in cellulose (c).(c) Cellulose: 1–4 linkage ofβglucose monomers.In cellulose, every βglucose monomer is upside down with respect to its neighbors. (See the highlighted OH groups.)▲Figure 5.7 Starch and cellulose structures.
72UNIT ONEThe Chemistry of Lifecellulose-digesting prokaryotes and protists in its gut. These microbes hydrolyze the cellulose of hay and grass and convert the glucose to other compounds that nourish the cow. Similarly, a termite, which is unable to digest cel-lulose by itself, has prokaryotes or protists living in its gut that can make a meal of wood. Some fungi can also digest cellulose in soil and elsewhere, thereby helping recycle chemical elements within Earth’s ecosystems.Another important structural polysaccharide is chitin, the carbohydrate used by arthropods (insects, spiders, crus-taceans, and related animals) to build their exoskeletons (Figure 5.8). An exoskeleton is a hard case that surrounds the soft parts of an animal. Made up of chitin embedded in a layer of proteins, the case is leathery and flexible at first, but becomes hardened when the proteins are chemically linked to each other (as in insects) or encrusted with calcium car-bonate (as in crabs). Chitin is also found in fungi, which use this polysaccharide rather than cellulose as the building ma-terial for their cell walls. Chitin is similar to cellulose, with βlinkages, except that the glucose monomer of chitin has a nitrogen-containing appendage (see Figure 5.8, top right). COCH3HNHOHOHCH2OHOHHHOHHuni25C0 Chitin, embedded in proteins, forms the exoskeleton of arthropods. This cicada is molting—shedding its old exoskeleton and emerging in adult form.uni25C0 The structure of the chitin monomeruni25B6 Chitin is used to make a strong and flexible surgical thread that decomposes after the wound or incision heals.▲Figure 5.8 Chitin, a structural polysaccharide.C O N C E P T C H E C K 5 . 21. Write the formula for a monosaccharide that has three carbons.2. A dehydration reaction joins two glucose molecules to form maltose. The formula for glucose is C6H12O6. What is the formula for maltose?3. W H AT I F ?After a cow is given antibiotics to treat an infection, a vet gives the animal a drink of “gut culture” containing various prokaryotes. Why is this necessary?For suggested answers, see Appendix A.C O N C E P T 5.3Lipids are a diverse group of hydrophobic moleculesLipids are the one class of large biological molecules that does not include true polymers, and they are generally not big enough to be considered macromolecules. The com-pounds called lipidsare grouped with each other because they share one important trait: They mix poorly, if at all, with water. The hydrophobic behavior of lipids is based on their molecular structure. Although they may have some polar bonds associated with oxygen, lipids consist mostly of hydrocarbon regions. Lipids are varied in form and function. They include waxes and certain pigments, but we will focus on the types of lipids that are most biologically important: fats, phospholipids, and steroids.FatsAlthough fats are not polymers, they are large molecules as-sembled from smaller molecules by dehydration reactions. A fatis constructed from two kinds of smaller molecules: glycerol and fatty acids (Figure 5.9a). Glycerol is an alcohol; each of its three carbons bears a hydroxyl group. A fatty acidhas a long carbon skeleton, usually 16 or 18 carbon atoms in length. The carbon at one end of the skeleton is part of a carboxyl group, the functional group that gives these molecules the name fatty acid. The rest of the skeleton consists of a hydrocarbon chain. The relatively nonpolar C¬H bonds in the hydrocarbon chains of fatty acids are the reason fats are hydrophobic. Fats separate from water because the water molecules hydrogen-bond to one another and exclude the fats. This is the reason that vegetable oil (a liquid fat) separates from the aqueous vinegar solution in a bottle of salad dressing. In making a fat, three fatty acid molecules are each joined to glycerol by an ester linkage, a bond formed by a dehy-dration reaction between a hydroxyl group and a carboxyl group. The resulting fat, also called a triacylglycerol, thus consists of three fatty acids linked to one glycerol molecule.
CHAPTER 5The Structure and Function of Large Biological Molecules 73(Still another name for a fat is triglyceride, a word often found in the list of ingredients on packaged foods.) The fatty acids in a fat can all be the same, or they can be of two or three different kinds, as in Figure 5.9b.The terms saturatedfats and unsaturatedfats are com-monly used in the context of nutrition (Figure 5.10). These terms refer to the structure of the hydrocarbon chains of the fatty acids. If there are no double bonds between carbon atoms composing a chain, then as many hydrogen atoms as possible are bonded to the carbon skeleton. Such a structure is said to be saturatedwith hydrogen, and the resulting fatty acid is therefore called a saturated fatty acid(Figure 5.10a). An unsaturated fatty acidhas one or more double bonds, with one fewer hydrogen atom on each double-bonded car-bon. Nearly all double bonds in naturally occurring fatty acids are cisdouble bonds, which cause a kink in the hydrocarbon chain wherever they occur (Figure 5.10b). (See Figure 4.7b to remind yourself about cisand transdouble bonds.) A fat made from saturated fatty acids is called a saturated fat. Most animal fats are saturated: The hydrocarbon chains of their fatty acids—the “tails” of the fat molecules—lack double bonds, and their flexibility allows the fat molecules to pack together tightly. Saturated animal fats—such as lard and butter—are solid at room temperature. In contrast, the fats of plants and fishes are generally unsaturated, mean-ing that they are built of one or more types of unsaturated fatty acids. Usually liquid at room temperature, plant and fish fats are referred to as oils—olive oil and cod liver oil are examples. The kinks where the cisdouble bonds are located prevent the molecules from packing together closely enough (a) One of three dehydration reactions in the synthesis of a fat CHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHHCOHOCHHCOHHCHOHHCHOHCHCHHH2OFatty acid(in this case, palmitic acid)GlycerolCOCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHHOCOCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHHOCOCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHCHHH(b) Fat molecule (triacylglycerol)Ester linkageOH▲Figure 5.9 The synthesis and structure of a fat, or triacyl-glycerol.The molecular building blocks of a fat are one molecule of glycerol and three molecules of fatty acids. (a)One water molecule is removed for each fatty acid joined to the glycerol. (b)A fat molecule with three fatty acid units, two of them identical. The carbons of the fatty acids are arranged zigzag to suggest the actual orientations of the four single bonds extending from each carbon (see Figure 4.3a).Cisdouble bondcauses bending.CHHCOHCHOHOCCCOOOStructural formula of an unsaturated fat moleculeCHHCOHCHOHOCCCOOOSpace-filling model of oleic acid, an unsaturated fatty acid(a) Saturated fatAt room temperature, the molecules of a saturated fat, such as the fat in butter, are packed closely together, forming a solid. (b) Unsaturated fatStructural formula of a saturated fat molecule (Each hydrocarbon chain is represented as a zigzag line, where each bend represents a carbon atom and hydrogens are not shown.)Space-filling model of stearic acid, a saturated fatty acid (red = oxygen, black = carbon, gray = hydrogen)At room temperature, the molecules of an unsaturated fat such as olive oil cannot pack together closely enough to solidify because of the kinks in some of their fatty acid hydrocarbon chains.▼Figure 5.10 Saturated and unsaturated fats and fatty acids.
74UNIT ONEThe Chemistry of Lifeto solidify at room temperature. The phrase “hydrogenated vegetable oils” on food labels means that unsaturated fats have been synthetically converted to saturated fats by add-ing hydrogen. Peanut butter, margarine, and many other products are hydrogenated to prevent lipids from separating out in liquid (oil) form.A diet rich in saturated fats is one of several factors that may contribute to the cardiovascular disease known as ath-erosclerosis. In this condition, deposits called plaques develop within the walls of blood vessels, causing inward bulges that impede blood flow and reduce the resilience of the vessels. Recent studies have shown that the process of hydrogenat-ing vegetable oils produces not only saturated fats but also unsaturated fats with transdouble bonds. These trans fatsmay contribute more than saturated fats to atherosclerosis (see Chapter 42) and other problems. Because trans fats are especially common in baked goods and processed foods, the U.S. Department of Agriculture requires nutritional labels to include information on trans fat content. Some U.S. cities and at least two countries—Denmark and Switzerland—have even banned the use of trans fats in restaurants.The major function of fats is energy storage. The hy-drocarbon chains of fats are similar to gasoline molecules and just as rich in energy. A gram of fat stores more than twice as much energy as a gram of a polysaccharide, such as starch. Because plants are relatively immobile, they can function with bulky energy storage in the form of starch. (Vegetable oils are generally obtained from seeds, where more compact storage is an asset to the plant.) Animals, however, must carry their energy stores with them, so there is an advantage to having a more compact reservoir of fuel—fat. Humans and other mammals stock their long-term food reserves in adipose cells (see Figure 4.6a), which swell and shrink as fat is deposited and withdrawn from storage. In addition to storing energy, adipose tissue also cushions such vital organs as the kidneys, and a layer of fat beneath the skin insulates the body. This subcutaneous layer is especially thick in whales, seals, and most other marine mammals, protecting them from cold ocean water.PhospholipidsCells as we know them could not exist without another type of lipid—phospholipids. Phospholipids are essential for cells because they are major constituents of cell mem-branes. Their structure provides a classic example of how form fits function at the molecular level. As shown in Figure 5.11, a phospholipidis similar to a fat molecule but has only two fatty acids attached to glycerol rather than three. The third hydroxyl group of glycerol is joined to a phosphate group, which has a negative electrical charge in the cell. Typically, an additional small charged or polar molecule is also linked to the phosphate group. Choline is one such molecule (see Figure 5.11), but there are many others as well, allowing formation of a variety of phospho-lipids that differ from each other. The two ends of phospholipids show different behavior toward water. The hydrocarbon tails are hydrophobic and are excluded from water. However, the phosphate group and its attachments form a hydrophilic head that has an af-finity for water. When phospholipids are added to water, they self-assemble into double-layered structures called CH2N(CH3)3CH2OPOCH2OCHOCH2OO–COCO+CholinePhosphateGlycerolFatty acidsHydrophilicheadKink due to cisdouble bondHydrophobictails(a) Structural formula(b) Space-filling model(c) Phospholipid symbolHydrophilic headHydrophobic tails(d) Phospholipid bilayer© Pearson Education, Inc.◀Figure 5.11 The structure of a phospholipid.A phospholipid has a hydrophilic (polar) head and two hydrophobic (nonpolar) tails. This particular phospholipid, called a phosphatidylcholine, has a cho-line attached to a phosphate group. Shown here are (a)the structural formula, (b)the space-filling model (yellow =phosphorus, blue =nitrogen), (c)the symbol for a phospholipid that will appear through-out this book, and (d)the bilayer structure formed by self-assembly of phospholipids in an aqueous environment.D R AW I TDraw an oval around the hydrophilic head of the space-filling model.
CHAPTER 5The Structure and Function of Large Biological Molecules 75“bilayers,” shielding their hydrophobic portions from water (Figure 5.11d). At the surface of a cell, phospholipids are arranged in a similar bilayer. The hydrophilic heads of the molecules are on the outside of the bilayer, in contact with the aqueous solutions inside and outside of the cell. The hydrophobic tails point toward the interior of the bilayer, away from the water. The phospholipid bilayer forms a boundary between the cell and its external environment; in fact, the existence of cells depends on the properties of phospholipids.SteroidsSteroidsare lipids characterized by a carbon skeleton consisting of four fused rings. Different steroids are distin-guished by the particular chemical groups attached to this ensemble of rings. Cholesterol, a type of steroid, is a crucial molecule in animals (Figure 5.12). It is a common compo-nent of animal cell membranes and is also the precursor from which other steroids, such as the vertebrate sex hormones, are synthesized. In vertebrates, cholesterol is synthesized in the liver and is also obtained from the diet. A high level of cholesterol in the blood may contribute to atherosclerosis. In fact, both saturated fats and trans fats exert their negative impact on health by affecting cholesterol levels. CH3HOCH3H3CCH3CH3▲Figure 5.12 Cholesterol, a steroid.Cholesterol is the molecule from which other steroids, including the sex hormones, are synthe-sized. Steroids vary in the chemical groups attached to their four inter-connected rings (shown in gold).M A K E C O N N E C T I O N SCompare cholesterol with the sex hor-mones shown in the figure at the beginning of Concept 4.3. Circle the chemical groups that cholesterol has in common with estradiol; put a square around the chemical groups that cholesterol has in common with testosterone.C O N C E P T C H E C K 5 . 31. Compare the structure of a fat (triglyceride) with that of a phospholipid.2. Why are human sex hormones considered lipids?3. W H AT I F ?Suppose a membrane surrounded an oil droplet, as it does in the cells of plant seeds and in some animal cells. Describe and explain the form it might take.For suggested answers, see Appendix A.C O N C E P T 5.4Proteins include a diversity of structures, resulting in a wide range of functionsNearly every dynamic function of a living being depends on proteins. In fact, the importance of proteins is underscored by their name, which comes from the Greek word proteios, meaning “first,” or “primary.” Proteins account for more than 50% of the dry mass of most cells, and they are instru-mental in almost everything organisms do. Some proteins speed up chemical reactions, while others play a role in defense, storage, transport, cellular communication, move-ment, or structural support. Figure 5.13shows examples of proteins with these functions, which you’ll learn more about in later chapters. Life would not be possible without enzymes, most of which are proteins. Enzymatic proteins regulate metabo-lism by acting as catalysts, chemical agents that selectively speed up chemical reactions without being consumed by the reaction. Because an enzyme can perform its function over and over again, these molecules can be thought of as workhorses that keep cells running by carrying out the pro-cesses of life.A human has tens of thousands of different proteins, each with a specific structure and function; proteins, in fact, are the most structurally sophisticated molecules known. Con-sistent with their diverse functions, they vary extensively in structure, each type of protein having a unique three-dimensional shape.Diverse as proteins are, they are all constructed from the same set of 20 amino acids, linked in unbranched polymers. The bond between amino acids is called a peptide bond, so a polymer of amino acids is called a polypeptide. A proteinis a biologically functional molecule made up of one or more polypeptides, each folded and coiled into a specific three-dimensional structure.Amino Acid Monomers All amino acids share a common structure. An amino acidis an organic molecule with both an amino group and a carboxyl group (see Figure 4.9). The figure at the right shows the gen-eral formula for an amino acid. At the center of the amino acid is an asym-metric carbon atom called the alpha(α) carbon. Its four different partners are an amino group, a carboxyl group, a hydrogen atom, and a variable group symbolized by R. The R group, also called the side chain, differs with each amino acid.OHOCCRHSide chain (R group)NαcarbonHHAminogroupCarboxyl group
76UNIT ONEThe Chemistry of LifeFigure 5.14shows the 20 amino acids that cells use to build their thousands of proteins. Here the amino groups and carboxyl groups are all depicted in ionized form, the way they usually exist at the pH found in a cell. The physical and chemical properties of the side chain determine the unique characteristics of a particular amino acid, thus affecting its functional role in a polypeptide. In Figure 5.14, the amino acids are grouped according to the properties of their side chains. One group consists of amino acids with nonpolar side chains, which are hydrophobic. Enzymatic proteinsStorage proteinsContractile and motor proteinsHormonal proteinsDefensive proteinsTransport proteinsStructural proteinsReceptor proteins30 uni03BCm60 uni03BCmFunction:Selective acceleration of chemical reactionsExample:Digestive enzymes catalyze the hydrolysis of bonds in food molecules.Function:Storage of amino acidsExamples:Casein, the protein of milk, is the major source of amino acids for baby mammals. Plants have storage proteins in their seeds. Ovalbumin is the protein of egg white, used as an amino acid source for the developing embryo.Function:MovementExamples:Motor proteins are responsible for the undulations of cilia and flagella. Actin and myosin proteins are responsible for the contrac-tion of muscles.Function:Coordination of an organism‘s activitiesExample:Insulin, a hormone secreted by the pancreas, causes other tissues to take up glucose, thus regulating blood sugar concentration.Function:Protection against diseaseExample:Antibodies inactivate and help destroy viruses and bacteria.Function:Transport of substancesExamples:Hemoglobin, the iron-containing protein of vertebrate blood, transports oxygen from the lungs to other parts of the body. Other proteins transport molecules across membranes, as shown here.Function:Support Examples:Keratin is the protein of hair, horns, feathers, and other skin appendages. Insects and spiders use silk fibers to make their cocoons and webs, respectively. Collagen and elastin proteins provide a fibrous framework in animal connective tissues.Function:Response of cell to chemical stimuliExample:Receptors built into the membrane of a nerve cell detect signaling molecules released by other nerve cells.EnzymeOvalbuminAmino acidsfor embryoTransport proteinSignaling moleculesCollagenReceptor proteinVirusBacteriumAntibodiesCell membraneHighblood sugarNormalblood sugarActinMuscle tissueConnective tissueMyosinInsulinsecreted▼Figure 5.13 An overview of protein functions.Another group consists of amino acids with polar side chains, which are hydrophilic. Acidic amino acids are those with side chains that are generally negative in charge due to the presence of a carboxyl group, which is usually dissoci-ated (ionized) at cellular pH. Basic amino acids have amino groups in their side chains that are generally positive in charge. (Notice that allamino acids have carboxyl groups and amino groups; the terms acidicand basicin this context refer only to groups in the side chains.) Because they are charged, acidic and basic side chains are also hydrophilic.
CHAPTER 5The Structure and Function of Large Biological Molecules 77CH2CH2SCH3Proline (Pro or P)Side chain(R group)CCO–HOHH3N+CCO–HOH3N+CH2CH2CH2NHCH2CH2H2CLeucine (Leu or L)Valine (Val or V)Alanine (Ala or A)Glycine (Gly or G)CCO–HOH3N+Methionine (Met or M)CCO–HOH3N+Serine (Ser or S)CCO–HOH3N+Threonine (Thr or T)CCO–HOH3N+Cysteine (Cys or C)CCO–HOH3N+Phenylalanine (Phe or F)CCO–HOH3N+CCO–HOH2N+Tryptophan (Trp or W)Isoleucine (Ile or I)CH3CCO–HOH3N+CH3CH3CHCCO–HOH3N+CCO–HOH3N+CH3CH3CHH3CCHCH3CH2OHCH2CCO–HOH3N+Aspartic acid (Asp or D)OHCH3CHSHCH2CCO–HOH3N+Tyrosine (Tyr or Y)CCO–HOH3N+Asparagine(Asn or N)CCO–HOH3N+Glutamine (Gln or Q)CH2NH2OCCH2CH2OHO–OCCH2CCO–HOH3N+Glutamic acid (Glu or E)CH2CCO–HOH3N+Lysine (Lys or K)CCO–HOH3N+Arginine (Arg or R)Acidic (negatively charged)O–CH2OCCH2CH2CH2CH2NH3+CH2CH2CCO–HOH3N+Histidine (His or H)CH2NHCH2NH2+CNH2NH+NHOCH2CNH2Basic (positively charged)Nonpolar side chains; hydrophobicPolar side chains; hydrophilicElectrically charged side chains; hydrophilic Since cysteine is only weakly polar, it is sometimes classified as a nonpolar amino acid.▼Figure 5.14 The 20 amino acids of proteins.The amino acids are grouped here according to the properties of their side chains (R groups) and shown in their prevailing ionic forms at pH 7.2, the pH within a cell. The three-letter and one-letter abbreviations for the amino acids are in parentheses. All of the amino acids used in proteins are Lenantiomers (see Figure 4.7c).
78UNIT ONEThe Chemistry of LifeHNHCHCOCH2CH2CH3SNCHCOCH2OHNHHCHCOOHSHPeptide bondCH2HOHHNHCHCOCH2CH2CH3Amino end(N-terminus)Carboxyl end(C-terminus)New peptidebond formingSNCHCOCH2OHNHHCHCOOHSHPeptide bondCH2Side chainsBack-boneH2O▲Figure 5.15 Making a polypeptide chain.Peptide bonds are formed by dehydration reactions, which link the carboxyl group of one amino acid to the amino group of the next. The peptide bonds are formed one at a time, starting with the amino acid at the amino end (N-terminus). The polypeptide has a repetitive backbone (purple) to which the amino acid side chains (yellow and green) are attached.D R AW I TLabel the three amino acids in the upper part of the figure using three-letter and one-letter codes. Circle and label the carboxyl and amino groups that will form the new peptide bond.Polypeptides (Amino Acid Polymers)Now that we have examined amino acids, let’s see how they are linked to form polymers (Figure 5.15). When two amino acids are positioned so that the carboxyl group of one is adja-cent to the amino group of the other, they can become joined by a dehydration reaction, with the removal of a water mol-ecule. The resulting covalent bond is called a peptide bond. Repeated over and over, this process yields a polypeptide, a polymer of many amino acids linked by peptide bonds. The repeating sequence of atoms highlighted in purple in Figure 5.15 is called the polypeptide backbone. Extending from this backbone are the different side chains (R groups) of the amino acids. Polypeptides range in length from a few amino acids to a thousand or more. Each specific polypeptide has a unique linear sequence of amino acids. Note that one end of the polypeptide chain has a free amino group, while the opposite end has a free carboxyl group. Thus, a polypep-tide of any length has a single amino end (N-terminus) and a single carboxyl end (C-terminus). In a polypeptide of any significant size, the side chains far outnumber the terminal groups, so the chemical nature of the molecule as a whole is determined by the kind and sequence of the side chains. The immense variety of polypeptides in nature illustrates an important concept introduced earlier—that cells can make many different polymers by linking a limited set of mono-mers into diverse sequences.Protein Structure and FunctionThe specific activities of proteins result from their intricate three-dimensional architecture, the simplest level of which is the sequence of their amino acids. The pioneer in deter-mining the amino acid sequence of proteins was Frederick Sanger, who, with his colleagues at Cambridge University in England, worked on the hormone insulin in the late 1940s and early 1950s. He used agents that break polypeptides at specific places, followed by chemical methods to determine the amino acid sequence in these small fragments. Sanger and his co-workers were able, after years of effort, to recon-struct the complete amino acid sequence of insulin. Since then, the steps involved in sequencing a polypeptide have been automated.Once we have learned the amino acid sequence of a polypeptide, what can it tell us about the three-dimensional structure (commonly referred to simply as the “structure”) of the protein and its function? The term polypeptideis not synonymous with the term protein. Even for a protein consisting of a single polypeptide, the relationship is some-what analogous to that between a long strand of yarn and a sweater of particular size and shape that can be knit from the yarn. A functional protein is not justa polypeptide chain, but one or more polypeptides precisely twisted, folded, and coiled into a molecule of unique shape, which can be shown in several different types of models (Figure 5.16). And it is the amino acid sequence of each polypeptide that determines what three-dimensional structure the protein will have under normal cellular conditions. When a cell synthesizes a polypeptide, the chain may fold spontaneously, assuming the functional structure for that protein. This folding is driven and reinforced by the forma-tion of various bonds between parts of the chain, which in turn depends on the sequence of amino acids. Many pro-teins are roughly spherical (globular proteins), while others are shaped like long fibers (fibrous proteins). Even within these broad categories, countless variations exist.A protein’s specific structure determines how it works. In almost every case, the function of a protein depends on its ability to recognize and bind to some other molecule. In an especially striking example of the marriage of form and
CHAPTER 5The Structure and Function of Large Biological Molecules 79function, Figure 5.17shows the exact match of shape be-tween an antibody (a protein in the body) and the particular foreign substance on a flu virus that the antibody binds to and marks for destruction. In Chapter 43, you’ll learn more about how the immune system generates antibodies that match the shapes of specific foreign molecules so well. Also, you may recall from Chapter 2 that natural signaling mol-ecules called endorphins bind to specific receptor proteins on the surface of brain cells in humans, producing euphoria and relieving pain. Morphine, heroin, and other opiate drugs are able to mimic endorphins because they all share a simi-lar shape with endorphins and can thus fit into and bind to endorphin receptors in the brain. This fit is very specific, something like a lock and key (see Figure 2.16). Thus, the function of a protein—for instance, the ability of a recep-tor protein to bind to a particular pain-relieving signaling molecule—is an emergent property resulting from exquisite molecular order. Four Levels of Protein StructureWith the goal of understanding the function of a protein, learning about its structure is often productive. In spite of their great diversity, all proteins share three superimposed levels of structure, known as primary, secondary, and ter-tiary structure. A fourth level, quaternary structure, arises ▲Figure 5.16 Structure of a protein, the enzyme lysozyme.Present in our sweat, tears, and saliva, lysozyme is an enzyme that helps prevent infection by binding to and catalyzing the de-struction of specific molecules on the surface of many kinds of bacteria. The groove is the part of the protein that recognizes and binds to the target molecules on bacterial walls.Groove(a) GrooveTargetmoleculeA ribbon modelshows how the single polypeptide chain folds and coils to form the functional protein. (The yellow lines represent disulfide bridges that stabilize the protein’s shape.)(b) A space-filling modelshows more clearly the globular shape seen in many proteins, as well as the specific three-dimensional structure unique to lysozyme.(c) In this view, a ribbon model is superimposed on a wireframe model, which shows the backbone with the side chains extending from it. The yellow structure is the target molecule.when a protein consists of two or more polypeptide chains. Figure 5.18describes these four levels of protein structure. Be sure to study this figure thoroughly before going on to the next section. Antibody proteinProtein from flu virus▲Figure 5.17 An antibody binding to a protein from a flu virus.A technique called X-ray crystallography was used to generate a computer model of an antibody protein (blue and orange, left) bound to a flu virus protein (green and yellow, right). Computer software was then used to back the images away from each other, revealing the exact complementarity of shape between the two protein surfaces.
Primary StructureLinear chain of amino acidsSecondary Structure Regions stabilized by hydrogen bonds between atoms of the polypeptide backboneHHHHCCCNHHHHOOCCCNNR+R1015202515304045506065708085901001051101251201155535R+H3NAmino endAminoacidsPrimary structure of transthyretinCCarboxyl endOGly Pro Thr Gly Thr Gly Glu Ser Lys CysProLeuMetValLysValGlyGluLeuHisGlyLeuThrThrGluGluGluPheValGluGlyIleTyrLysValGluIleLeuAspAlaValArgGlySerProAlaIleAsnValValHisValPheArgLysAla75AspThrLysSerTyrTyrSerThrThrAla Val Val Thr Asn Pro Lys GluTrp Lys Ala Leu GlyIleSer Pro Phe His Glu His Ala Glu ValAla Asp Asp Thr Trp Glu Pro Phe Ala Ser Gly Lys Thr Ser Glu Ser95PheThrAlaAsnAspSerGlyProArgArgTyrThrIleAlaAlaLeuLeuSerProTyrSerValAlaOO–The primary structureof a protein is its sequence of amino acids. As an example, let’s consider transthyretin, a globular blood protein that transports vitamin A and one of the thyroid hormones throughout the body. Transthyretin is made up of four identical polypeptide chains, each composed of 127 amino acids. Shown here is one of these chains unraveled for a closer look at its primary structure. Each of the 127 positions along the chain is occupied by one of the 20 amino acids, indicated here by its three-letter abbreviation.The primary structure is like the order of letters in a very long word. If left to chance, there would be 20127different ways of making a polypeptide chain 127 amino acids long. However, the precise primary structure of a protein is determined not by the random linking of amino acids, but by inherited genetic informa-tion. The primary structure in turn dictates secondary and tertiary structure, due to the chemical nature of the backbone and the side chains (R groups) of the amino acids along the polypeptide.Most proteins have segments of their polypeptide chains repeatedly coiled or folded in patterns that contribute to the protein’s overall shape. These coils and folds, collectively referred to as secondary structure, are the result of hydrogen bonds between the repeat-ing constituents of the polypeptide backbone (not the amino acid side chains). Within the backbone, the oxygen atoms have a partial negative charge, and the hydrogen atoms attached to the nitrogens have a partial positive charge (see Figure 2.14); therefore, hydrogen bonds can form between these atoms. Individually, these hydro-gen bonds are weak, but because there are so many of them over a relatively long region of the polypeptide chain, they can support a particular shape for that part of the protein.One such secondary structure is the 𝛂𝛂helix, a delicate coil held together by hydrogen bonding between every fourth amino acid, as shown above. Although each transthyretin polypeptide has only one αhelix region (see tertiary structure), other globular proteins have multiple stretches of αhelix separated by nonhelical regions (see hemoglobin on the next page). Some fibrous proteins, such as α-keratin, the structural protein of hair, have the αhelix structure over most of their length.The other main type of secondary structure is the 𝛃𝛃pleated sheet. As shown above, in this structure two or more segments of the polypeptide chain lying side by side (called βstrands) are con-nected by hydrogen bonds between parts of the two parallel seg-ments of the polypeptide backbone. βpleated sheets make up the core of many globular proteins, as is the case for transthyretin (see tertiary structure), and dominate some fibrous proteins, includ-ing the silk protein of a spider’s web. The teamwork of so many hydrogen bonds makes each spider silk fiber stronger than a steel strand of the same weight.β strand, often shown as a flatarrow pointing toward the carboxyend (here, shown folded)βpleated sheetαhelixHydrogen bondHydrogen bond▼ Spiders secrete silk fibers made of a structural protein containing βpleated sheets, which allow the spider web to stretch and recoil.▼Figure 5.18Exploring Levels of Protein Structure80
HemeIronαsubunitβsubunitβsubunitαsubunitHemoglobinTertiary StructureThree-dimensional shape stabilized by interactions between side chainsQuaternary StructureAssociation of two or more polypeptides (some proteins only)Superimposed on the patterns of secondary structure is a protein’s tertiary structure, shown above in a ribbon model of the transthyretin polypeptide. While secondary structure involves interactions between backbone constituents, tertiary structureis the overall shape of a polypeptide resulting from interactions between the side chains (R groups) of the various amino acids. One type of interaction that contributes to tertiary structure is called—somewhat misleadingly— a hydrophobic interaction. As a polypeptide folds into its functional shape, amino acids with hydrophobic (nonpolar) side chains usually end up in clusters at the core of the protein, out of contact with water. Thus, a “hydrophobic interaction” is actually caused by the exclusion of nonpolar substances by water molecules. Once nonpolar amino acid side chains are close together, van der Waals interactions help hold them together. Meanwhile, hydrogen bonds between polar side chains and ionic bonds between positively and negatively charged side chains also help stabilize tertiary structure. These are all weak interac-tions in the aqueous cellular environment, but their cumulative effect helps give the protein a unique shape.Covalent bonds called disulfide bridgesmay further reinforce the shape of a protein. Disulfide bridges form where two cysteine monomers, which have sulfhydryl groups (¬SH) on their side chains (see Figure 4.9), are brought close together by the folding of the protein. The sulfur of one cysteine bonds to the sulfur of the sec-ond, and the disulfide bridge (¬S¬S¬) rivets parts of the protein together (see the yellow lines in Figure 5.16a). All of these different kinds of interactions can contribute to the tertiary structure of a pro-tein, as shown here in a small part of a hypothetical protein:Some proteins consist of two or more polypeptide chains aggregated into one functional macromolecule. Quaternary structureis the overall protein structure that results from the aggregation of these polypeptide subunits. For example, shown above is the complete globular transthyretin protein, made up of its four polypeptides.Another example is collagen, shown below, which is a fibrous protein that has three identical helical polypeptides intertwined into a larger triple helix, giving the long fibers great strength. This suits collagen fibers to their function as the girders of connective tissue in skin, bone, tendons, ligaments, and other body parts. (Collagen accounts for 40% of the protein in a human body.)TransthyretinpolypeptideTransthyretinprotein(four identicalpolypeptides)HydrogenbondHydrophobicinteractions andvan der WaalsinteractionsIonic bondDisulfidebridgePolypeptidebackboneOHCH2SCH2SCH2OCH2CNH2CH3CH3CHCH3CH3CHO–CH2OCCH2CH2CH2CH2NH3+Hemoglobin, the oxygen-binding protein of red blood cells shown below, is another example of a globular protein with quaternary structure. It consists of four polypeptide subunits, two of one kind (α) and two of another kind (β). Both αand βsubunits consist primarily of α-helical secondary structure. Each subunit has a nonpolypeptide component, called heme, with an iron atom that binds oxygen.Collagen81
82UNIT ONEThe Chemistry of LifeNormal proteinDenatured proteinDenaturationRenaturation▲Figure 5.20 Denaturation and renaturation of a protein.High temperatures or various chemical treatments will denature a pro-tein, causing it to lose its shape and hence its ability to function. If the denatured protein remains dissolved, it may renature when the chemi-cal and physical aspects of its environment are restored to normal.Sickle-Cell Disease: A Change in Primary StructureEven a slight change in primary structure can affect a pro-tein’s shape and ability to function. For instance, sickle-cell disease, an inherited blood disorder, is caused by the sub-stitution of one amino acid (valine) for the normal one (glu-tamic acid) at a particular position in the primary structure of hemoglobin, the protein that carries oxygen in red blood cells. Normal red blood cells are disk-shaped, but in sickle-cell disease, the abnormal hemoglobin molecules tend to ag-gregate into chains, deforming some of the cells into a sickle shape (Figure 5.19). A person with the disease has periodic “sickle-cell crises” when the angular cells clog tiny blood vessels, impeding blood flow. The toll taken on such patients is a dramatic example of how a simple change in protein structure can have devastating effects on protein function. What Determines Protein Structure?You’ve learned that a unique shape endows each protein with a specific function. But what are the key factors determin-ing protein structure? You already know most of the answer: A polypeptide chain of a given amino acid sequence can be arranged into a three-dimensional shape determined by the interactions responsible for secondary and tertiary structure. This folding normally occurs as the protein is being synthe-sized in the crowded environment within a cell, aided by other proteins. However, protein structure also depends on the physical and chemical conditions of the protein’s envi-ronment. If the pH, salt concentration, temperature, or other aspects of its environment are altered, the weak chemical bonds and interactions within a protein may be destroyed, causing the protein to unravel and lose its native shape, a change called denaturation(Figure 5.20). Because it is mis-shapen, the denatured protein is biologically inactive. Most proteins become denatured if they are transferred from an aqueous environment to a nonpolar solvent, such as ether or chloroform; the polypeptide chain refolds so that its hydrophobic regions face outward toward the solvent. Other denaturation agents include chemicals that disrupt Val1His2Leu3Thr4Pro5Glu6Glu7Val1His2Leu3Thr4Pro5Val6Glu7Normal hemoglobinSickle-cellhemoglobinSickle-cell βsubunitNormal βsubunitNormal hemoglobin proteins donot associate with one another;each carries oxygen.ααββααββ5 uni03BCmNormal hemoglobinSickle-cell hemoglobinPrimaryStructureSecondary andTertiary StructuresQuaternaryStructureFunctionRed Blood Cell ShapeNormal red blood cells are full of individual hemoglobin proteins.Fibers of abnormal hemoglobin deform red blood cell into sickle shape.Hydrophobic interactions between sickle-cell hemoglobin proteins lead to their aggregation into a fiber; capacity to carry oxygen is greatly reduced.5 uni03BCm▲Figure 5.19 A single amino acid substitution in a protein causes sickle-cell disease.M A K E C O N N E C T I O N SConsidering the chemical characteristics of the amino acids valine and glutamic acid (see Figure 5.14), propose a possible explanation for the dramatic effect on protein function that occurs when valine is substituted for glutamic acid.
CHAPTER 5The Structure and Function of Large Biological Molecules 83the hydrogen bonds, ionic bonds, and disulfide bridges that maintain a protein’s shape. Denaturation can also result from excessive heat, which agitates the polypeptide chain enough to overpower the weak interactions that stabilize the structure. The white of an egg becomes opaque during cooking because the denatured proteins are insoluble and solidify. This also explains why excessively high fevers can be fatal: Proteins in the blood tend to denature at very high body temperatures.When a protein in a test-tube solution has been dena-tured by heat or chemicals, it can sometimes return to its functional shape when the denaturing agent is removed. (Sometimes this is not possible: For example, a fried egg will not become liquefied when placed back into the refrigera-tor!) We can conclude that the information for building specific shape is intrinsic to the protein’s primary struc-ture. The sequence of amino acids determines the protein’s shape—where an α helix can form, where βpleated sheets can exist, where disulfide bridges are located, where ionic bonds can form, and so on. But how does protein folding occur in the cell?Protein Folding in the CellBiochemists now know the amino acid sequence for more than 24 million proteins, with about 1 million added each month, and the three-dimensional shape for more than 25,000. Researchers have tried to correlate the primary structure of many proteins with their three-dimensional structure to discover the rules of protein folding. Unfortu-nately, however, the protein-folding process is not that sim-ple. Most proteins probably go through several intermediate structures on their way to a stable shape, and looking at the mature structure does not reveal the stages of folding re-quired to achieve that form. However, biochemists have de-veloped methods for tracking a protein through such stages.Crucial to the folding process are chaperonins(also called chaperone proteins), protein molecules that assist in the proper folding of other proteins (Figure 5.21). Chap-eronins do not specify the final structure of a polypeptide. Instead, they keep the new polypeptide segregated from dis-ruptive chemical conditions in the cytoplasmic environment while it folds spontaneously. The chaperonin shown in Figure 5.21, from the bacterium E. coli, is a giant multi-protein complex shaped like a hollow cylinder. The cavity provides a shelter for folding polypeptides, and recent re-search suggests that minute amounts of water are present, ensuring a hydrophilic environment that aids the folding process. Molecular systems have been identified that inter-act with chaperonins and check whether proper folding has occurred. Such systems either refold the misfolded proteins correctly or mark them for destruction. Misfolding of polypeptides is a serious problem in cells that has come under increasing scrutiny by medical re-searchers. Many diseases—such as cystic fibrosis, Alzheim-er’s, Parkinson’s, and mad cow disease—are associated with an accumulation of misfolded proteins. In fact, misfolded versions of the transthyretin protein featured in Figure 5.18 have been implicated in several diseases, including one form of senile dementia.Even when scientists have a correctly folded protein in hand, determining its exact three-dimensional structure is not simple, for a single protein molecule has thousands of atoms. The first 3-D structures were worked out in the late 1950s for hemoglobin and a related protein called myoglobin. The method that made these feats possible was X-ray crystallography, which has since been used to determine the 3-D structure of many other proteins. In a recent example, Roger Kornberg and his colleagues at Stanford University used this method to elucidate the structure of RNA poly-merase, an enzyme that plays a crucial role in the expression of genes (Figure 5.22). Another method for analyzing protein structure is nuclear magnetic resonance (NMR) spectroscopy, which does not require protein crystallization. A still newer approach employs bioinformatics (see Concept 5.6) to pre-dict the 3-D structure of polypeptides from their amino acid sequence. X-ray crystallography, NMR spectroscopy, and bio-informatics are complementary approaches to understanding protein structure and function. PolypeptideCorrectly foldedproteinHollowcylinderChaperonin(fully assembled)CapAn unfolded poly-peptide enters thecylinder from one end.1Cap attachment causes the cylinder to change shape, creating a hydrophilic environ-ment for polypeptide folding.23The cap comesoff, and the properlyfolded protein isreleased.▶Figure 5.21 A chaperonin in action.The computer graphic (left) shows a large chaperonin protein complex from the bacterium E. coli. It has an interior space that provides a shelter for the proper folding of newly made polypeptides. The complex consists of two proteins: One is a hollow cylinder; the other is a cap that can fit on either end. The steps of chaperonin activity are shown at the right.
84UNIT ONEThe Chemistry of LifeRNARNApolymerase IIDNADiffracted X-raysDigital detectorX-ray diffractionpatternCrystalX-raybeamX-raysourceInquiryWhat can the 3-D shape of the enzyme RNA polymerase II tell us about its function?▼ Figure 5.22ExperimentIn 2006, Roger Kornberg was awarded the Nobel Prize in Chemistry for using X-ray crystallography to determine the 3-D shape of RNA polymerase II, which binds to the DNA double helix and synthesizes RNA. After crystallizing a complex of all three components, Kornberg and his colleagues aimed an X-ray beam through the crystal. The atoms of the crystal diffracted (bent) the X-rays into an orderly array that a digital detector recorded as a pattern of spots called an X-ray diffraction pattern.ResultsUsing data from X-ray diffraction patterns, as well as the amino acid sequence determined by chemical methods, the researchers built a 3-D model of the complex with the help of computer software.ConclusionAnalysis of the model led to a hypothesis about the functions of different regions of RNA polymerase II. For example, the region above the DNA may act as a clamp that holds the nucleic acids in place. (You’ll learn more about this enzyme in Chapter 17.)Source: A. L. Gnatt et al., Structural basis of transcription: an RNA polymerase II elon-gation complex at 3.3Å, Science292:1876–1882 (2001). Computer graphic copyright © 2001 by AAAS. Reprinted with permission.W H AT I F ?Looking at the model, can you identify any elements of secondary structure?C O N C E P T C H E C K 5 . 41. What parts of a polypeptide participate in the bonds that hold together secondary structure? Tertiary structure?2. Thus far in the chapter, the Greek letters αand βhave been used to specify at least three different pairs of struc-tures. Name and briefly describe them.3. W H AT I F ?Where would you expect a polypeptide region rich in the amino acids valine, leucine, and isoleu-cine to be located in a folded polypeptide? Explain.For suggested answers, see Appendix A.C O N C E P T 5.5Nucleic acids store, transmit, and help express hereditary informationIf the primary structure of polypeptides determines a pro-tein’s shape, what determines primary structure? The amino acid sequence of a polypeptide is programmed by a discrete unit of inheritance known as a gene. Genes consist of DNA, which belongs to the class of compounds called nucleic acids. Nucleic acidsare polymers made of monomers called nucleotides.The Roles of Nucleic AcidsThe two types of nucleic acids, deoxyribonucleic acid (DNA)and ribonucleic acid (RNA), enable living organisms to reproduce their complex components from one genera-tion to the next. Unique among molecules, DNA provides directions for its own replication. DNA also directs RNA synthesis and, through RNA, controls protein synthesis; this entire process is called gene expression(Figure 5.23). DNA is the genetic material that organisms inherit from their parents. Each chromosome contains one long DNA molecule, usually carrying several hundred or more genes. When a cell reproduces itself by dividing, its DNA mol-ecules are copied and passed along from one generation of 1mRNARibosomeAminoacidsPolypeptideCYTOPLASMDNAmRNANUCLEUSSynthesis ofmRNA in the nucleus 1Movement ofmRNA into cytoplasmvia nuclear pore 2Synthesis of protein using informationcarried onmRNA 3▲Figure 5.23 Gene expression: DNA SRNA Sprotein.In a eukaryotic cell, DNA in the nucleus programs protein production in the cytoplasm by dictating synthesis of messenger RNA (mRNA).
CHAPTER 5The Structure and Function of Large Biological Molecules 85nucleus and the plasma membrane (the cytoplasm), but DNA resides in the nucleus. Messenger RNA conveys genetic instructions for building proteins from the nucleus to the cytoplasm. Prokaryotic cells lack nuclei but still use mRNA to convey a message from the DNA to ribosomes and other cellular equipment that translate the coded information into amino acid sequences. In Chapter 18, you’ll read about other functions of some recently discovered RNA molecules.The Components of Nucleic AcidsNucleic acids are macromolecules that exist as polymers called polynucleotides(Figure 5.24a). As indicated by the name, each polynucleotide consists of monomers called nucleotides. A nucleotide, in general, is composed of three parts: a five-carbon sugar (a pentose), a nitrogen-containing (nitrogenous) base, and one or more phosphate groups (Figure 5.24b). In a polynucleotide, each monomer has only one phosphate group. The portion of a nucleotide without any phosphate groups is called a nucleoside. To build a nucleotide, let’s first consider the nitrogenous bases (Figure 5.24c). Each nitrogenous base has one or two rings that include nitrogen atoms. (They are called nitrog-enous basesbecause the nitrogen atoms tend to take up cells to the next. Encoded in the structure of DNA is the information that programs all the cell’s activities. The DNA, however, is not directly involved in running the operations of the cell, any more than computer software by itself can read the bar code on a box of cereal. Just as a scanner is needed to read a bar code, proteins are required to imple-ment genetic programs. The molecular hardware of the cell—the tools for biological functions—consists mostly of proteins. For example, the oxygen carrier in red blood cells is the protein hemoglobin that you saw earlier (see Figure 5.17), not the DNA that specifies its structure.How does RNA, the other type of nucleic acid, fit into gene expression, the flow of genetic information from DNA to proteins? Each gene along a DNA molecule directs syn-thesis of a type of RNA called messengerRNA(mRNA). The mRNA molecule interacts with the cell’s protein-synthesizing machinery to direct production of a polypeptide, which folds into all or part of a protein. We can summarize the flow of genetic information as DNA SRNA Sprotein (see Figure 5.23). The sites of protein synthesis are cellular structures called ribosomes. (In the Unit 1 interview before Chapter 2, Venki Ramakrishnan describes how the structure of ribosomes was determined by X-ray crystallography.) In a eukaryotic cell, ribosomes are in the region between the (a) Polynucleotide, or nucleic acid(b) Nucleotide(c) Nucleoside componentsNH2NH2NH2CCNHOCHCHNCNHOCCHHNCCH3OCNHOCHCHHNCOOCytosine (C)NITROGENOUS BASESPyrimidinesSUGARSPurinesThymine (T, in DNA)CNCCNCHCAdenine (A)Deoxyribose (in DNA)Ribose (in RNA)NNHCNCNHCHCHCNNHGuanine (G)NitrogenousbaseNucleoside5‘ end3‘ end5‘CSugar(pentose)PhosphategroupSugar-phosphate backbone(on blue background)OO–P–OOOHCH2OOOOO4‘1‘5‘3‘2‘HOCH2HOCH2OHHHHOHHHO4‘1‘5‘3‘2‘OHHHHOHHOHOUracil (U, in RNA)3‘C3‘C1‘C5‘C5‘C3‘C▼Figure 5.24 Components of nucleic acids.(a)A polynucleotide has a sugar-phosphate backbone with variable appendages, the nitrog-enous bases. (b)A nucleotide monomer includes a nitrogenous base, a sugar, and a phosphate group. Note that carbon numbers in the sugar include primes (′). (c)A nucleoside includes a nitrogenous base (purine or pyrimidine) and a five-carbon sugar (deoxyribose or ribose).
86UNIT ONEThe Chemistry of LifeH+from solution, thus acting as bases.) There are two families of nitrogenous bases: pyrimidines and purines. A pyrimidinehas one six-membered ring of carbon and ni-trogen atoms. The members of the pyrimidine family are cytosine (C), thymine (T), and uracil (U). Purinesare larger, with a six-membered ring fused to a five-membered ring. The purines are adenine (A) and guanine (G). The specific pyrimidines and purines differ in the chemical groups at-tached to the rings. Adenine, guanine, and cytosine are found in both DNA and RNA; thymine is found only in DNA and uracil only in RNA.Now let’s add the sugar to which the nitrogenous base is attached. In DNA the sugar is deoxyribose; in RNA it is ribose(see Figure 5.24c). The only difference between these two sugars is that deoxyribose lacks an oxygen atom on the second carbon in the ring; hence the name deoxyribose.So far, we have built a nucleoside (nitrogenous base plus sugar). To complete the construction of a nucleotide, we attach a phosphate group to the 5′carbon of the sugar (see Figure 5.24b). The molecule is now a nucleoside monophos-phate, more often called a nucleotide.Nucleotide PolymersThe linkage of nucleotides into a polynucleotide involves a dehydration reaction. (You will learn the details in Chapter 16). In the polynucleotide, adjacent nucleotides are joined by a phosphodiester linkage, which consists of a phosphate group that links the sugars of two nucleotides. This bonding results in a repeating pattern of sugar-phosphate units called the sugar-phosphate backbone(see Figure 5.24a). (Note that the nitrogenous bases are not part of the backbone.) The two free ends of the polymer are distinctly different from each other. One end has a phosphate attached to a 5′carbon, and the other end has a hydroxyl group on a 3′carbon; we refer to these as the 5′endand the 3′end, respectively. We can say that a polynucleotide has a built-in directionality along its sugar-phosphate backbone, from 5′to 3′, somewhat like a one-way street. All along this sugar-phosphate backbone are appendages consisting of the nitrogenous bases.The sequence of bases along a DNA (or mRNA) polymer is unique for each gene and provides very specific informa-tion to the cell. Because genes are hundreds to thousands of nucleotides long, the number of possible base sequences is effectively limitless. A gene’s meaning to the cell is encoded in its specific sequence of the four DNA bases. For ex-ample, the sequence 5′-AGGTAACTT-3′means one thing, whereas the sequence 5′-CGCTTTAAC-3′has a different meaning. (Entire genes, of course, are much longer.) The linear order of bases in a gene specifies the amino acid sequence—the primary structure—of a protein, which in turn specifies that protein’s three-dimensional structure and its function in the cell.The Structures of DNA and RNA MoleculesDNA molecules have two polynucleotides, or “strands,” that wind around an imaginary axis, forming a double helix(Figure 5.25a). The two sugar-phosphate backbones run in opposite 5′→3′directions from each other; this arrange-ment is referred to as antiparallel, somewhat like a divided highway. The sugar-phosphate backbones are on the outside of the helix, and the nitrogenous bases are paired in the interior of the helix. The two strands are held together by hydrogen bonds between the paired bases (see Figure 5.25a). Most DNA molecules are very long, with thousands or even millions of base pairs. For example, the one long DNA dou-ble helix in a eukaryotic chromosome includes many genes, each one a particular segment of the molecule. In base pairing, only certain bases in the double helix are compatible with each other. Adenine (A) in one strand always pairs with thymine (T) in the other, and guanine (G) always pairs with cytosine (C). Reading the sequence of bases along one strand of the double helix would tell us the sequence of bases along the other strand. If a stretch of one strand has the base sequence 5′-AGGTCCG-3′, then the base-pairing rules tell us that the same stretch of the other strand must have the sequence 3′-TCCAGGC-5′. The two strands of the double helix are complementary, each the predictable counterpart of the other. It is this feature of DNA that makes it possible to generate two identical copies of each DNA molecule in a cell that is preparing to divide. When the cell divides, the copies are distributed to the daughter cells, making them genetically identical to the parent cell. Thus, the structure of DNA accounts for its function of transmitting genetic information whenever a cell reproduces.RNA molecules, by contrast, exist as single strands. Complementary base pairing can occur, however, be-tween regions of two RNA molecules or even between two stretches of nucleotides in the sameRNA molecule. In fact, base pairing within an RNA molecule allows it to take on the particular three-dimensional shape necessary for its func-tion. Consider, for example, the type of RNA called transfer RNA(tRNA), which brings amino acids to the ribosome dur-ing the synthesis of a polypeptide. A tRNA molecule is about 80 nucleotides in length. Its functional shape results from base pairing between nucleotides where complementary stretches of the molecule can run antiparallel to each other (Figure 5.25b).Note that in RNA, adenine (A) pairs with uracil (U); thy-mine (T) is not present in RNA. Another difference between RNA and DNA is that DNA almost always exists as a double helix, whereas RNA molecules are more variable in shape. RNAs are very versatile molecules, and many biologists be-lieve RNA may have preceded DNA as the carrier of genetic information in early forms of life (see Concept 25.1).
CHAPTER 5The Structure and Function of Large Biological Molecules 87G(a) DNA(b) Transfer RNAATCGCTCGTAUAASugar-phosphatebackbonesBase pair joinedby hydrogen bondingBase pair joinedby hydrogen bondingHydrogen bonds5uni20323uni20325uni20323uni2032GGCC▶Figure 5.25 The structures of DNA and tRNA molecules.(a)The DNA molecule is usually a double helix, with the sugar- phosphate backbones of the antiparallel poly-nucleotide strands (symbolized here by blue ribbons) on the outside of the helix. Hydrogen bonds between pairs of nitrogenous bases hold the two strands together. As illustrated here with symbolic shapes for the bases, adenine (A) can pair only with thymine (T), and guanine (G) can pair only with cytosine (C). Each DNA strand in this figure is the structural equivalent of the polynucleotide diagrammed in Figure 5.24a. (b)A tRNA molecule has a roughly L-shaped structure, with complementary base pairing of antiparallel stretches of RNA. In RNA, A pairs with U.C O N C E P T C H E C K 5 . 51. D R AW I TGo to Figure 5.24a and, for the top three nucleotides, number all the carbons in the sugars, circle the nitrogenous bases, and star the phosphates.2. D R AW I TIn a DNA double helix, a region along one DNA strand has this sequence of nitrogenous bases: 5′-TAGGCCT-3′. Copy this sequence, and write down its complementary strand, clearly indicating the 5′and 3′ends of the complementary strand.For suggested answers, see Appendix A.C O N C E P T 5.6Genomics and proteomics have transformed biological inquiry and applicationsExperimental work in the first half of the 20th century es-tablished the role of DNA as the bearer of genetic informa-tion, passed from generation to generation, that specified the functioning of living cells and organisms. Once the structure of the DNA molecule was described in 1953, and the linear sequence of nucleotide bases was understood to specify the amino acid sequence of proteins, biologists sought to “decode” genes by learning their base sequences.The first chemical techniques for DNA sequencing, or de-termining the sequence of nucleotides along a DNA strand, one by one, were developed in the 1970s. Researchers began to study gene sequences, gene by gene, and the more they learned, the more questions they had: How was expression of genes regulated? Genes and their protein products clearly interacted with each other, but how? What was the function, if any, of the DNA that is not part of genes? To fully under-stand the genetic functioning of a living organism, the entire sequence of the full complement of DNA, the organism’s genome, would be most enlightening. In spite of the apparent impracticality of this idea, in the late 1980s several promi-nent biologists put forth an audacious proposal to launch a project that would sequence the entire human genome—all 3 billion bases of it! This endeavor began in 1990 and was ef-fectively completed in the early 2000s.An unplanned but profound side benefit of this project—the Human Genome Project—was the rapid development of faster and less expensive methods of sequencing. This trend has continued apace: The cost for sequencing 1 million bases in 2001, well over $5,000, has decreased to less than $0.10 in 2012. And a human genome, the first of which took over 10 years to sequence, could be completed at today’s pace in just a few days. The number of genomes that have been fully sequenced has burgeoned, generating reams of data and prompting development of bioinformatics, the use of computer software and other computational tools that can handle and analyze these large data sets.The reverberations of these developments have trans-formed the study of biology and related fields. Biologists often look at problems by analyzing large sets of genes or even comparing whole genomes of different species, an ap-proach called genomics. A similar analysis of large sets of proteins, including their sequences, is called proteomics. (Protein sequences can be determined either by using bio-chemical techniques or by translating the DNA sequences that code for them.) These approaches permeate all fields of biology, some examples of which are shown in Figure 5.26. Perhaps the most significant impact of genomics and proteomics on the field of biology as a whole has been their contributions to our understanding of evolution. In addition to confirming evidence for evolution from the study of fos-sils and characteristics of currently existing species, genom-ics has helped us tease out relationships among different groups of organisms that had not been resolved by previous types of evidence, and thus infer evolutionary history.
Contributions of Genomicsand Proteomics to BiologyContributions of Genomicsand Proteomics to BiologyThe tools of molecular genetics and genomics are increasingly used by ecologists to identify which species of animals and plants are killed illegally. In one case, genomic sequences of DNA from illegal shipments of elephant tusks were used to track down poachers and pinpoint the territory where they were operating.Over 90% of all plant species exist in a mutually beneficial partnership with fungi that are associated with the plants’ roots. Genome sequencing and analysis of gene expression in several plant-fungal pairs promise major advances in our understanding of such interactions and may have implications for agricultural practices.New DNA sequencing techniques have allowed decoding of minute quantities of DNA found in ancient tissues from our extinct relatives, the Neanderthals (Homo neanderthalensis). Sequencing the Neander-thal genome has informed our understanding of their physical appearance as well as their relationship with modern humans.A major aim of evolutionary biology is to under-stand the relationships among species, both living and extinct. For example, genome sequence comparisons have identified the hippopotamus as the land mammal sharing the most recent common ancestor with whales.Nucleotide sequencing and the analysis of large sets of genes and proteins can be done rapidly and inexpensively due to advances in technology and informa-tion processing. Taken together, genomics and proteomics have advanced our understanding of biology across many different fields.Conservation BiologyPaleontologyEvolutionMedical ScienceSpecies InteractionsIdentifying the genetic basis for human diseases like cancer helps researchers focus their search for potential future treatments. Currently, sequencing the sets of genes expressed in an individual’s tumor can allow a more targeted approach to treating the cancer, a type of “personalized medicine.” HippopotamusShort-finned pilot whaleSee Figure 22.20.See Figure 56.9.(See the Scientific SkillsExercise in Chapter 31.)See Figure 34.49.See Figures 12.20 and 18.27.88UNIT ONEThe Chemistry of Life▼Figure 5.26M A K E C O N N E C T I O N SM A K E C O N N E C T I O N SConsidering the examples provided here, describe how the approaches of genomics and proteomics help us to address a variety of biological questions.
CHAPTER 5The Structure and Function of Large Biological Molecules 89corresponding hemoglobin polypeptide in other vertebrates. In this chain of 146 amino acids, humans and gorillas differ in just 1 amino acid, while humans and frogs, more distantly related, differ in 67 amino acids. In the Scientific Skills Exer-cise, you can apply this sort of reasoning to additional spe-cies. And this conclusion holds true as well when comparing whole genomes: The human genome is 95–98% identical to that of the chimpanzee, but only roughly 85% identical to that of the mouse, a more distant evolutionary relative. Mo-lecular biology has added a new tape measure to the toolkit biologists use to assess evolutionary kinship. DNA and Proteins as Tape Measures of EvolutionE VO L U T I O NWe are accustomed to thinking of shared traits, such as hair and milk production in mammals, as evi-dence of shared ancestry. Because DNA carries heritable in-formation in the form of genes, sequences of genes and their protein products document the hereditary background of an organism. The linear sequences of nucleotides in DNA mol-ecules are passed from parents to offspring; these sequences determine the amino acid sequences of proteins. As a result, siblings have greater similarity in their DNA and proteins than do unrelated individuals of the same species.Given our evolutionary view of life, we can extend this concept of “molecular genealogy” to relationships between species: We would expect two species that appear to be closely related based on anatomical evidence (and possibly fossil evidence) to also share a greater proportion of their DNA and protein sequences than do less closely related spe-cies. In fact, that is the case. An example is the comparison of the βpolypeptide chain of human hemoglobin with the S C I E N T I F I C S K I L L S E X E R C I S EAre Rhesus Monkeys or Gibbons More Closely Related to Humans? DNA and polypeptide sequences from closely related species are more similar to each other than are sequences from more distantly related species. In this exercise, you will look at amino acid sequence data for the βpolypeptide chain of hemoglobin, often called β-globin. You will then interpret the data to hypothesize whether the monkey or the gibbon is more closely related to humans.How Such Experiments Are Done Researchers can isolate the poly-peptide of interest from an organism and then determine the amino acid sequence. More frequently, the DNA of the relevant gene is sequenced, and the amino acid sequence of the polypeptide is deduced from the DNA sequence of its gene.Data from the Experiments In the data below, the letters give the sequence of the 146 amino acids in β-globin from humans, rhesus Analyzing Polypeptide Sequence Datamonkeys, and gibbons. Because a complete sequence would not fit on one line here, the sequences are broken into three segments. The se-quences for the three different species are aligned so that you can com-pare them easily. For example, you can see that for all three species, the first amino acid is V (valine) and the 146th amino acid is H (histidine). Interpret the Data 1. Scan the monkey and gibbon sequences, letter by letter, circling any amino acids that do not match the human sequence. (a) How many amino acids differ between the monkey and the human sequences? (b) Between the gibbon and human?2. For each nonhuman species, what percent of its amino acids are identical to the human sequence of β-globin?3. Based on these data alone, state a hypothesis for which of these two species is more closely related to humans. What is your reasoning?Species Alignment of Amino Acid Sequences of u1D6C3-globinHuman 1 VHLTPEEKSA VTALWGKVNV DEVGGEALGR LLVVYPWTQR FFESFGDLSTMonkey 1 VHLTPEEKNA VTTLWGKVNV DEVGGEALGR LLLVYPWTQR FFESFGDLSSGibbon 1 VHLTPEEKSA VTALWGKVNV DEVGGEALGR LLVVYPWTQR FFESFGDLSTHuman 51 PDAVMGNPKV KAHGKKVLGA FSDGLAHLDN LKGTFATLSE LHCDKLHVDPMonkey 51 PDAVMGNPKV KAHGKKVLGA FSDGLNHLDN LKGTFAQLSE LHCDKLHVDPGibbon 51 PDAVMGNPKV KAHGKKVLGA FSDGLAHLDN LKGTFAQLSE LHCDKLHVDPHuman 101 ENFRLLGNVL VCVLAHHFGK EFTPPVQAAY QKVVAGVANA LAHKYHMonkey 101 ENFKLLGNVL VCVLAHHFGK EFTPQVQAAY QKVVAGVANA LAHKYHGibbon 101 ENFRLLGNVL VCVLAHHFGK EFTPQVQAAY QKVVAGVANA LAHKYH4. What other evidence could you use to support your hypothesis?A version of this Sci-entific Skills Exercise can be assigned in MasteringBiology.Data fromHuman: http://www.ncbi.nlm.nih.gov/protein/AAA21113.1; rhesus mon-key: http://www.ncbi.nlm.nih.gov/protein/122634; gibbon: http://www.ncbi.nlm.nih.gov/protein/122616uni25B6Humanuni25B6Rhesus monkeyuni25B6GibbonC O N C E P T C H E C K 5 . 61. How would sequencing the entire genome of an organ-ism help scientists to understand how that organism functioned?2. Given the function of DNA, why would you expect two species with very similar traits to also have very similar genomes?For suggested answers, see Appendix A.
components of lipids vary. Monomers form larger molecules by dehydration reactions, in which water molecules are released. Polymers can disassemble by the reverse process, hydrolysis. An immense variety of polymers can be built from a small set of monomers.?What is the fundamental basis for the differences between large carbohydrates, proteins, and nucleic acids?SUMMARY OF KEY CONCEPTSC O N C E P T5.1Macromolecules are polymers, built from monomers (pp. 67–68)•Large carbohydrates (polysaccharides), proteins, and nucleic acids are polymers, which are chains of monomers. The Chapter Review5Large Biological MoleculesComponentsExamplesFunctionsC O N C E P T 5.2Carbohydrates serve as fuel and building material (pp. 68–72)?Compare the composition, structure, and function of starch and cellulose. What role do starch and cellulose play in the human body? Monosaccharides:glucose,fructoseFuel; carbon sources that can beconverted to other molecules orcombined into polymers Disaccharides:lactose, sucrose Polysaccharides:•Cellulose (plants)•Starch (plants)•Glycogen (animals)•Chitin (animals and fungi)•Strengthens plant cell walls•Stores glucose for energy•Stores glucose for energy•Strengthens exoskeletons andfungal cell wallsC O N C E P T 5.3Lipids are a diverse group of hydrophobic molecules (pp. 72–75)?Why are lipids not considered to be polymers or macromolecules? Triacylglycerols(fats or oils):glycerol+3 fatty acidsImportant energy source Phospholipids:glycerol+phosphate group+2 fatty acidsLipid bilayers of membranes Steroids:four fused rings withattached chemical groups•Component of cell membranes(cholesterol)•Signaling molecules that travelthrough the body (hormones)C O N C E P T 5.4Proteins include a diversity of structures, resulting in a wide range of functions (pp. 75–84)?Explain the basis for the great diversity of proteins. •Enzymes•Structural proteins•Hormones•Receptor proteins•Motor proteins•Defensive proteins•Catalyze chemical reactions•Provide structural support•Coordinate organismal responses•Receive signals from outside cell•Function in cell movement•Protect against diseaseC O N C E P T 5.5Nucleic acids store, transmit, and help express hereditary information (pp. 84–87)?What role does complementary base pairing play in the functions of nucleic acids? DNA:•Sugar=deoxyribose•Nitrogenous bases=C, G, A, T•Usually double-strandedStores hereditary informationRNA:•Sugar=ribose•Nitrogenous bases=C, G, A, U•Usually single-strandedVarious functions in gene expression,including carrying instructions fromDNA to ribosomesMonosaccharide monomerOHHHOHOHCH2OHOHHHHOHydrophobictailsHydrophilicheads2 fatty acidsHeadwith PGlycerol3 fatty acidsNitrogenous baseSugarNucleotide monomerPhosphategroupCH2OPOHOCCRHNHHAmino acid monomer(20 types)Steroid backbone90UNIT ONEThe Chemistry of Life
CHAPTER 5The Structure and Function of Large Biological Molecules 91C O N C E P T 5.6Genomics and proteomics have transformed biological inquiry and applications (pp. 87–89)•Recent technological advances in DNA sequencing have given rise to genomics, an approach that analyzes large sets of genes or whole genomes, and proteomics, a similar approach for large sets of proteins. Bioinformatics is the use of computational tools and computer software to analyze these large data sets.•The more closely two species are related evolutionarily, the more similar their DNA sequences are. DNA sequence data confirms models of evolution based on fossils and anatomical evidence.?Given the sequences of a particular gene in fruit flies, fish, mice, and humans, predict the relative similarity of the human sequence to that of each of the other species.TEST YOUR UNDERSTANDINGLEVEL 1: KNOWLEDGE/COMPREHENSION1. Which of the following categories includes all others in the list?a. monosaccharideb. polysaccharide8. Construct a table that organizes the following terms, and label the columns and rows.MonosaccharidesFatty acidsAmino acidsNucleotidesGiven that the function of egg yolk is to nourish and support the developing chick, explain why egg yolks are so high in fat, protein, and cholesterol.For selected answers, see Appendix A.9. D R AW I TCopy the polynucleotide strand in Figure 5.24a and label the bases G, T, C, and T, starting from the 5′end. Assum-ing this is a DNA polynucleotide, now draw the complemen-tary strand, using the same symbols for phosphates (circles), sugars (pentagons), and bases. Label the bases. Draw arrows showing the 5′S3′direction of each strand. Use the arrows to make sure the second strand is antiparallel to the first. Hint: After you draw the first strand vertically, turn the paper upside down; it is easier to draw the second strand from the 5′toward the 3′direction as you go from top to bottom.LEVEL 3: SYNTHESIS/EVALUATION10. EVOLUTION CONNECTION Comparisons of amino acid sequences can shed light on the evolutionary divergence of related species. If you were compar-ing two living species, would you expect all proteins to show the same degree of divergence? Why or why not?11. SCIENTIFIC INQUIRY Suppose you are a research assistant in a lab studying DNA-binding proteins. You have been given the amino acid se-quences of all the proteins encoded by the genome of a certain species and have been asked to find candidate proteins that could bind DNA. What type of amino acids would you expect to see in the DNA-binding regions of such proteins? Why?12. WRITE ABOUT A THEME: ORGANIZATION Proteins, which have diverse functions in a cell, are all poly-mers of the same kinds of monomers—amino acids. Write a short essay (100–150 words) that discusses how the structure of amino acids allows this one type of polymer to perform so many functions.13. SYNTHESIZE YOUR KNOWLEDGE PolypeptidesTriacylglycerolsPolynucleotidesPolysaccharidesPhosphodiester linkagesPeptide bondsGlycosidic linkagesEster linkages2. The enzyme amylase can break glycosidic linkages between glucose monomers only if the monomers are in the α form. Which of the following could amylase break down?a. glycogen, starch, and amylopectinb. glycogen and cellulosec. cellulose and chitind. starch, chitin, and cellulose3. Which of the following is true of unsaturatedfats?a. They are more common in animals than in plants.b. They have double bonds in the carbon chains of their fatty acids.c. They generally solidify at room temperature.d. They contain more hydrogen than do saturated fats having the same number of carbon atoms.4. The structural level of a protein leastaffected by a disruption in hydrogen bonding is thea. primary level.b. secondary level.c. starchd. carbohydratec. tertiary level.d. quaternary level.5. Enzymes that break down DNA catalyze the hydrolysis of the covalent bonds that join nucleotides together. What would happen to DNA molecules treated with these enzymes?a. The two strands of the double helix would separate.b. The phosphodiester linkages of the polynucleotide back-bone would be broken.c. The pyrimidines would be separated from the deoxyribose sugars.d. All bases would be separated from the deoxyribose sugars.LEVEL 2: APPLICATION/ANALYSIS6. The molecular formula for glucose is C6H12O6. What would be the molecular formula for a polymer made by linking ten glucose molecules together by dehydration reactions?a. C60H120O60b. C60H102O51c. C60H100O50d. C60H111O517. Which of the following pairs of base sequences could form a short stretch of a normal double helix of DNA?a. 5′-AGCT-3′with 5′-TCGA-3′b. 5′-GCGC-3′with 5′-TATA-3′c. 5′-ATGC-3′with 5′-GCAT-3′d. All of these pairs are correct.Students Go to MasteringBiologyfor assignments, the eText, and the Study Area with practice tests, animations, and activities.Instructors Go to MasteringBiologyfor automatically graded tutorials and questions that you can assign to your students, plus Instructor Resources.