Campbell Biology 12th Edition, PDF - Large Biological Molecules

5 The Structure and Function of Large Biological Molecules KEY CONCEPTS 5.1 Macromolecules are polymers, built from monomers p. 67 5.2 Carbohydrates serve as fuel and building material p. 68 5.3 Lipids are a diverse group of hydrophobic molecules p. 72 5.4 Proteins include a diversity of s...

5 The Structure and Function of Large Biological Molecules KEY CONCEPTS 5.1 Macromolecules are polymers, built from monomers p. 67 5.2 Carbohydrates serve as fuel and building material p. 68 5.3 Lipids are a diverse group of hydrophobic molecules p. 72 5.4 Proteins include a diversity of structures, resulting in a wide range of functions p. 75 5.5 Nucleic acids store, transmit, and help express hereditary information p. 84 5.6 Genomics and proteomics have transformed biological inquiry and applications p. 86 Study Tip Make a visual study guide: For each class of biological molecules, draw two examples and list their structural similarities and their functions. Important Biological Molecules Carbohydrates Proteins Figure 5.1 Alcohol dehydrogenase, a protein that breaks down alcohol in the body, is shown here as a molecular model. The form of this protein that an individual possesses affects how well that person tolerates drinking alcohol. Proteins are one class of large molecules, or macromolecules. What are the structures and functions of the four important classes of biological molecules? Three classes are macromolecules that are polymers (long chains of monomer subunits). Monomer Polymer Nucleic acids Lipids Carbohydrates are a source of energy and provide structural support. Glucose Carbohydrate (starch) Nucleic acids Go to Mastering Biology For Students (in eText and Study Area) • Animation: Making and Breaking Polymers • Figure 5.11 Walkthrough: The Structure of a Phospholipid • BioFlix® Animation: Gene Expression For Instructors to Assign (in Item Library) • Molecular Model: Lysozyme • Tutorial: Nucleic Acid Structure 66 store genetic information and function in gene expression. Nucleotide Proteins have a wide range of functions, such as catalyzing reactions and transporting substances into and out of cells. Protein (alcohol dehydrogenase) The fourth class, lipids, are not polymers or macromolecules. Lipids are a group of Nucleic acid (DNA) Amino acid diverse molecules that do not mix well with water. Key functions include providing energy, making up cell membranes, and acting as Lipid hormones. (phospholipid) CONCEPT . Figure 5.2 The synthesis and breakdown of carbohydrate and protein polymers. 5.1 Macromolecules are polymers, built from monomers (a) Dehydration reaction: synthesizing a polymer Large carbohydrates, proteins, and nucleic acids, also known as macromolecules for their huge size, are chain-like molecules called polymers (from the Greek polys, many, and meros, part). A polymer is a long molecule consisting of many similar or identical building blocks linked by covalent bonds, much as a train consists of a chain of boxcars. The repeating units that serve as the building blocks of a polymer are smaller molecules called monomers (from the Greek monos, single). In addition to forming polymers, some monomers have functions of their own. HO 1 2 3 H Short polymer HO Unlinked monomer Dehydration removes a water molecule, forming a new bond. HO 1 H 2 3 H2O 4 H 4 H Longer polymer (b) Hydrolysis: breaking down a polymer The Synthesis and Breakdown of Polymers Although each class of polymer is made up of a different type of monomer, the chemical mechanisms by which cells make polymers (polymerization) and break them down are similar for all classes of large biological molecules. In cells, these processes are facilitated by enzymes, specialized macromolecules (usually proteins) that speed up chemical reactions. The reaction that connects a monomer to another monomer or a polymer is a condensation reaction, a reaction in which two molecules are covalently bonded to each other with the loss of a small molecule. If a water molecule is lost, it is known as a dehydration reaction. For example, carbohydrate and protein polymers are synthesized by dehydration reactions. Each reactant contributes part of the water molecule that is released during the reaction: One provides a hydroxyl group (—OH), while the other provides a hydrogen (—H) (Figure 5.2a). This reaction is repeated as monomers are added to the chain one by one, lengthening the 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. (Dehydration reactions and hydrolysis can also be involved in the formation and breakdown of molecules that are not polymers, such as some lipids.) The Diversity of Polymers A cell has thousands of different macromolecules; the collection varies from one type of cell to another. The inherited CHAPTER 5 HO 1 2 3 H2O Hydrolysis adds a water molecule, breaking a bond. HO 1 2 3 H HO H Mastering Biology Animation: Making and Breaking Polymers differences between close relatives, such as human siblings, reflect small variations in polymers, particularly DNA and proteins. Molecular differences between unrelated individuals 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 common 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 thousands 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 describing the great diversity of macromolecules because most biological polymers have many more monomers than the number of letters in even the longest word. 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 molecules common to all organisms act as building blocks that 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 components. The Structure and Function of Large Biological Molecules 67 CONCEPT CHECK 5.1 1. What are the four main classes of large biological molecules? 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. WHAT IF? 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? . Figure 5.3 The structure and classification of some monosaccharides. Sugars vary in the location of their carbonyl groups (orange), the length of their carbon skeletons, and the way their parts are arranged spatially around asymmetric carbons (compare, for example, the purple portions of glucose and galactose). Aldoses (Aldehyde Sugars) Carbonyl group at end of carbon skeleton For suggested answers, see Appendix A. CONCEPT Trioses: three-carbon sugars (C3H6O3) 5.2 H Carbohydrates include 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. C OH H C OH The Chemistry of Life H C OH C O C OH H H Glyceraldehyde An initial breakdown product of glucose Dihydroxyacetone An initial breakdown product of glucose Pentoses: five-carbon sugars (C5H10O5) H H O H C Sugars UNIT ONE H H Mastering Biology Animation: Carbohydrates 68 H O C Carbohydrates serve as fuel and building material Monosaccharides (from the Greek monos, single, and sacchar, sugar) generally have molecular formulas that are some multiple of the unit CH2 O. Glucose (C6 H12 O6), 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 monosaccharide: The molecule has a carbonyl group, l C “ O, and multiple hydroxyl groups, —OH (Figure 5.3). √ Depending on the location of the carbonyl group, a monosaccharide 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.) Another criterion for classifying monosaccharides 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 way their parts are arranged spatially around asymmetric carbons. (Recall that an asymmetric carbon is a carbon attached 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 significant enough to give the two sugars distinctive shapes and binding activities, thus different behaviors. Although it is convenient to draw glucose with a linear carbon skeleton, this representation is not completely accurate. In aqueous solutions, glucose molecules, as well as most other Ketoses (Ketone Sugars) Carbonyl group within carbon skeleton C OH C O H C OH H C OH H C OH H C OH H C OH H C OH H C OH H H Ribose A component of RNA Ribulose An intermediate in photosynthesis Hexoses: six-carbon sugars (C6H12O6) H O H C C H O H C OH C O H C OH H HO C H HO C H C OH HO C H H C OH H C OH H C OH H C OH H C OH H C OH H C OH H C OH HO C H H H Glucose Galactose Energy sources for organisms H Fructose An energy source for organisms MAKE CONNECTIONS In 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 processed food, is a mixture of glucose and fructose. What type of isomers are glucose and fructose? (See Figure 4.7.) Mastering Biology Animation: Monosaccharides . Figure 5.4 Linear and ring forms of glucose. H O 1C H HO 3 C H H 4 C OH H 5 C OH H 6 C OH C 6 CH2OH 6 CH2OH 2 OH H 4C OH 5C O H OH H H 1C H OH 4C O 2 3C H H 5C OH C 3C OH H H CH2OH 6 O H H 4 1C H 2 HO OH 2 H OH H 1 H 3 OH C O 5 H OH OH (b) 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. H (a) Linear 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. DRAW IT Start with the linear form of fructose (see Figure 5.3) and draw the formation of the fructose ring in two steps, as shown in (a). First, number the carbons starting at the top of the linear structure. Then draw the molecule in a ringlike orientation, attaching carbon 5 via its oxygen to carbon 2. Compare the number of carbons in the ring portions of fructose and glucose. A disaccharide consists of two monosaccharides joined by a glycosidic linkage, a covalent bond formed between two monosaccharides by a dehydration reaction (glyco refers to carbohydrate). For example, maltose is a disaccharide formed by the linking of two molecules of glucose (Figure 5.5a). Also known as malt sugar, maltose is an ingredient used in brewing beer. The most prevalent disaccharide is sucrose, or table sugar. Its two monomers are glucose and fructose (Figure 5.5b). Plants generally 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 five- and six-carbon sugars, form rings, because they are the most stable form of these sugars under physiological conditions (Figure 5.4). Monosaccharides, particularly glucose, are major nutrients 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 monosaccharides a major fuel for cellular work, but their carbon skeletons also serve as raw material for the synthesis of other types of small organic molecules, such as amino acids and fatty acids. Monosaccharides that are not immediately used in these ways are generally incorporated as monomers into disaccharides or polysaccharides, discussed next. . Figure 5.5 Examples of disaccharide synthesis. (a) Dehydration reaction in CH2OH the synthesis of maltose. O H The bonding of two glucose H H units forms maltose. The 1–4 H glycosidic linkage joins the OH H OH HO HO number 1 carbon of one glucose to the number 4 H OH carbon of the second glucose. H2O Joining the glucose monomers in a different way would reGlucose 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. CH2OH H HO O H OH H H CH2OH O O H OH H H H OH HO OH H HO H OH H H H HO CH2OH DRAW IT Referring to Figures 5.3 and 5.4, number the carbons in each sugar in this figure. How does the name of each linkage relate to the numbers? CHAPTER 5 H 4 O H OH H H OH H OH Maltose H Fructose CH2OH OH CH2OH H 1– 4 H glycosidic 1 linkage O Glucose OH H2O H OH CH2OH O OH Glucose CH2OH H HO O H OH H 1– 2 H glycosidic 1 linkage CH2OH O 2 H H HO CH2OH O H OH OH H Sucrose Mastering Biology Animation: Synthesis of Sucrose The Structure and Function of Large Biological Molecules 69 to a galactose molecule. Disaccharides must be broken down into monosaccharides to be used for energy by organisms. Lactose intolerance is a common condition in humans who lack lactase, the enzyme that breaks down lactose. The sugar is instead broken down by intestinal bacteria, causing formation of gas and subsequent cramping. The problem may be avoided by taking the enzyme lactase when eating or drinking dairy products or consuming dairy products that have already been treated with lactase to break down the lactose. Polysaccharides Polysaccharides are macromolecules, polymers with a few hundred to a few thousand monosaccharides joined by glycosidic linkages. Some polysaccharides serve as storage material, hydrolyzed as needed to provide monosaccharides 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 monosaccharides and by the positions of its glycosidic linkages. Storage Polysaccharides Both 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. (Plastids include chloroplasts.) Synthesizing starch enables the plant to stockpile surplus glucose. Because glucose is a major cellular fuel, starch represents stored energy. The sugar can later be withdrawn by the plant from this carbohydrate “bank” by hydrolysis, which breaks the bonds between the glucose monomers. Most animals, including humans, also have enzymes that can hydrolyze plant starch, making glucose . 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 1–4 linkages between glucose molecules. There are two kinds of starch: amylose and amylopectin. Cellulose, with a different kind of glucose linkage, is always unbranched. Storage structures (plastids) containing starch granules in a potato tuber cell Amylose (unbranched) O O O O O O O O (a) Starch O Muscle tissue O O O O O O O O O O O Glucose monomer Amylopectin (somewhat branched) O O O O 50 om O O O O O O O O Glycogen (extensively branched) Glycogen granules stored in muscle tissue O O O O O 1 om O (b) Glycogen Plant cell, surrounded by cell wall 10 om Microfibril (bundle of about 80 cellulose molecules) UNIT ONE O O O O O O O O The Chemistry of Life O O Cellulose molecule (unbranched) O OH O OH O O O O (c) Cellulose O O O O Cellulose microfibrils in a plant cell wall 0.5 om 70 O O O O O O Cell wall O O O O O O Hydrogen bonds between parallel cellulose molecules hold them together. O O O O O O O O O O difference is based on the fact that there are actually two slightly different 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 (a) and beta (b), 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 a 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 b configuration, 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. Certain starch molecules are largely helical, fitting their function of efficiently storing glucose units. Conversely, a cellulose 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 molecules 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 microfibrils are a strong building material for plants and an important substance for humans because cellulose is the major constituent of paper and the only component of cotton. The unbranched structure of cellulose thus fits its function: imparting strength to parts of the plant. Enzymes that digest starch by hydrolyzing its a linkages are unable to hydrolyze the b linkages of cellulose due to the different shapes of these two molecules. In fact, available as a nutrient for cells. Potato tubers and grains—the fruits of wheat, maize (corn), rice, and other grasses—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 linkages at the branch points. Both of these starches are shown in Figure 5.6a. Animals store a polysaccharide called glycogen, a polymer of glucose that is like amylopectin but more extensively branched (Figure 5.6b). Vertebrates store glycogen mainly in liver and muscle cells. Breakdown of glycogen in these cells releases glucose when the demand for energy increases. (The extensively branched structure of glycogen fits its function: More free ends are available for breakdown.) 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 eating. This is an issue of concern in lowcarbohydrate diets, which can result in weakness and fatigue. Structural Polysaccharides Organisms build strong materials from structural polysaccharides. For example, the polysaccharide called cellulose is a major component of the tough walls that enclose plant cells (Figure 5.6c). Globally, plants produce almost 10 14 kg (100 billion tons) of cellulose per year; it is the most abundant organic compound on Earth. Like starch, cellulose is a polymer of glucose with 1–4 glycosidic linkages, but the linkages in these two polymers differ. The . Figure 5.7 Starch and cellulose structures. (a) c and d glucose ring structures. These two interconvertible forms of glucose differ in the placement of the hydroxyl group (highlighted in blue) attached to the number 1 carbon. H CH2OH H 4 HO O H OH H C OH HO C H H 1 H OH c Glucose OH H O C CH2OH H H OH 4 H C OH H C OH H C OH HO O OH H 1 “Insoluble Fiber” listed on food labels is mainly cellulose, shown below. H Nutrition Facts d Glucose H OH Dietary Fiber 4g 16% Soluble Fiber 2g Insoluble Fiber 2g H CH2OH O HO CH2OH O 1 4 OH O OH OH CH2OH O O OH OH CH2OH O O OH OH CH2OH O OH OH (b) Starch: 1–4 linkage of c glucose monomers. All monomers are in the same orientation. Compare the positions of the OH groups highlighted in yellow with those in cellulose (c). HO OH O 1 4 OH O OH CH2OH O OH CH2OH O OH OH O OH O OH OH CH2OH (c) Cellulose: 1–4 linkage of d glucose monomers. In cellulose, every d glucose monomer is upside down with respect to its neighbors. (See the highlighted OH groups.) Mastering Biology Animation: Starch, Cellulose, and Glycogen Structures CHAPTER 5 The Structure and Function of Large Biological Molecules 71 few organisms 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 healthy diet. Most fruits, vegetables, and whole grains are rich in cellulose. On food packages, “insoluble fiber” refers mainly to cellulose (see Figure 5.7). Some microorganisms can digest cellulose, breaking it down into glucose monomers. A cow harbors cellulosedigesting 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 cellulose 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, crustaceans, and related animals) to build their exoskeletons—hard cases that surround the soft parts of an animal (Figure 5.8). 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 carbonate (as in crabs). Chitin is also found in fungi, which use this polysaccharide rather than cellulose as the building material for their cell walls. Chitin is similar to cellulose, with b linkages, except that the glucose monomer of chitin has a nitrogen-containing attachment (see Figure 5.8). . Figure 5.8 Chitin, a structural polysaccharide. CH2OH H HO O H OH H H NH OH C b The structure of the chitin monomer H O CH3 b Chitin, embedded in proteins, forms the exoskeleton of arthropods. This emperor dragonfly (Anax imperator) is molting—shedding its old exoskeleton (brown) and emerging upside down in adult form. 72 UNIT ONE The Chemistry of Life CONCEPT CHECK 5.2 1. 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 C 6H12O6. What is the formula for maltose? 3. WHAT IF? 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. CONCEPT 5.3 Lipids are a diverse group of hydrophobic molecules Lipids 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 compounds called lipids are grouped with each other because they share one important trait: They are hydrophobic: They mix poorly, if at all, with water. This 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 with relatively non-polar C—H bonds. 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 important biologically: fats, phospholipids, and steroids. Mastering Biology Animation: Lipids Fats Although fats are not polymers, they are large molecules assembled from smaller molecules by dehydration reactions, like the dehydration reaction described in Figure 5.2a. A fat consists of a glycerol molecule joined to three fatty acids (Figure 5.9). Glycerol is an alcohol; each of its three carbons bears a hydroxyl group. A fatty acid has 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 why vegetable oil (a liquid fat) separates from the aqueous vinegar solution in a bottle of salad dressing. In making a fat, each fatty acid molecule is joined to glycerol by a dehydration reaction (Figure 5.9a). This results in an ester linkage, a bond between a hydroxyl group and a carboxyl group. The completed fat consists of three fatty acids linked to one glycerol molecule. (Other names for a fat are triacylglycerol and triglyceride; levels of triglycerides are . Figure 5.9 The synthesis and structure of a fat, or triacylglycerol. The molecular building blocks of a fat are one molecule of glycerol and three molecules of fatty acids. The carbons of the fatty acids are arranged zigzag to suggest the actual orientations of the four single bonds extending from each carbon (see Figures 4.3a and 4.6b). H O H C OH H C OH H C OH H H C C HO H C C H H H H C C H H H H C C H H H H C C H H H H C C H H H H C C H H H H C C H H H H Glycerol (a) One of three dehydration reactions in the synthesis of a fat. One water molecule is removed for each fatty acid joined to the glycerol. Ester linkage H H C O O C H C H O H C O C H C H O H C H O C H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C C H H H H C H O H C O C H C O C H C O C O O H 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. H C Structural formula of a saturated fat molecule (Each hydrocarbon chain is represented as a zigzag line, where each bend represents a carbon atom; hydrogens are not shown.) (b) Unsaturated fat H H H At room temperature, the molecules of a saturated fat, such as the fat in butter, are packed closely together, forming a solid. H H C (a) Saturated fat H Fatty acid (in this case, palmitic acid) H2O . Figure 5.10 Saturated and unsaturated fats and fatty acids. H H (b) A fat molecule (triacylglycerol) with three fatty acid units. In this example, two of the fatty acid units are identical. reported when blood is tested for lipids.) 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 saturated fats and unsaturated fats are commonly 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 saturated with hydrogen, and the resulting fatty acid is therefore called a saturated fatty acid (Figure 5.10a). An unsaturated fatty acid has one or more double bonds, with one fewer hydrogen atom on each double-bonded carbon. Nearly every double bond in naturally occurring fatty acids is a cis double bond, which creates a kink in the hydrocarbon chain wherever it occurs (Figure 5.10b). (See Figure 4.7b to remind yourself about cis and trans double 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 (see Figure 5.10a), and their flexibility allows the fat molecules to pack together tightly. Saturated animal CHAPTER 5 H Structural formula of an unsaturated fat molecule O H C O C H C O C H C O C O O H Space-filling model of oleic acid, an unsaturated fatty acid Cis double bond causes bending. fats, such as lard and butter, are solid at room temperature. In contrast, the fats of plants and fishes are generally unsaturated, meaning that they are composed 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 cis double bonds are located (see Figure 5.10b) prevent the molecules from packing together closely enough to solidify at room temperature. The phrase hydrogenated vegetable oils on food labels means that The Structure and Function of Large Biological Molecules 73 unsaturated fats have been synthetically converted to saturated fats by adding hydrogen, allowing them to solidify. 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 atherosclerosis. 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. The process of hydrogenating vegetable oils produces not only saturated fats but also unsaturated fats with trans double bonds. It appears that trans fats can contribute to coronary heart disease (see Concept 42.4). Because trans fats are especially common in baked goods and processed foods, the U.S. Food and Drug Administration (FDA) requires nutritional labels to include information on trans fat content. In addition, the FDA has ordered U.S. food manufacturers to stop producing trans fats in foods by 2021. Some countries, such as Denmark and Switzerland, have already banned artificially produced trans fats in foods. The major function of fats is energy storage. The hydrocarbon 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 CH2 Choline O O O– P Phosphate O CH2 CH O O C O C CH2 Glycerol Cells as we know them could not exist without another type of lipid, called phospholipids. Phospholipids are essential for cells because they are major constituents of cell membranes. Their structure provides a classic example of how form fits function at the molecular level. As shown in Figure 5.11, a phospholipid is 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 phospholipids that differ from each other. The two ends of phospholipids show different behaviors with respect to 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 affinity for water. When phospholipids are added to water, they self-assemble into a double-layered sheet called a “bilayer” that shields their hydrophobic fatty acid tails from water (Figure 5.11d). DRAW IT Draw an oval around the hydrophilic head of the space-filling model. O Mastering Biology Figure Walkthrough Animation: Space-Filling Model of a Phospholipid Fatty acids Hydrophobic tails Hydrophilic head N(CH3)3 Phospholipids . 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 choline 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 throughout this book, and (d) the bilayer structure formed by selfassembly of phospholipids in an aqueous environment. + CH2 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, insulating their bodies in cold ocean water. Kink due to cis double bond Hydrophilic head Hydrophobic tails (a) Structural formula 74 UNIT ONE The Chemistry of Life (b) Space-filling model (c) Phospholipid symbol (d) Phospholipid bilayer 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 and establishes separate compartments within eukaryotic cells; in fact, the existence of cells depends on the properties of phospholipids. Steroids Steroids are lipids characterized by a carbon skeleton consisting of four fused rings. Different steroids are distinguished 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 component 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, although some researchers are questioning the roles of cholesterol and saturated fats in the development of this condition. . Figure 5.12 Cholesterol, a steroid. Cholesterol is the molecule from which other steroids, including the sex hormones, are synthesized. Steroids vary in the chemical groups attached to their four interconnected rings (shown in gold). CH3 H3C CH3 CH3 CH3 HO MAKE CONNECTIONS Compare cholesterol with the sex hormones 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. Mastering Biology Interview with Lovell Jones: Investigating the effects of sex hormones on cancer CONCEPT CHECK 5.3 1. Compare the structure of a fat (triglyceride) with that of a phospholipid. 2. Why are human sex hormones considered lipids? 3. WHAT IF? 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. CHAPTER 5 CONCEPT 5.4 Proteins include a diversity of structures, resulting in a wide range of functions Nearly 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 instrumental in almost everything organisms do. Some proteins speed up chemical reactions, while others play a role in defense, storage, transport, cellular communication, movement, or structural support. Figure 5.13 shows 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 metabolism by acting as catalysts, chemical agents that selectively speed up chemical reactions without being consumed in 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 processes 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. Consistent with their diverse functions, they vary extensively in structure, each type of protein having a unique threedimensional shape. Proteins 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 protein is a biologically functional molecule made up of one or more polypeptides, each folded and coiled into a specific threedimensional structure. Amino Acids (Monomers) All amino acids share a common Side chain (R group) structure. An amino acid is an R organic molecule with both an amino c carbon group and a carboxyl group (see O Figure 4.9); the small figure shows H C C N the general formula for an amino H OH acid. At the center of the amino acid H is an asymmetric carbon atom called Amino Carboxyl group group the alpha (a) 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. The R group may be as simple as a The Structure and Function of Large Biological Molecules 75 . Figure 5.13 An overview of protein functions. Mastering Biology Animation: Protein Functions Enzymatic proteins Defensive proteins Function: Selective acceleration of chemical reactions Example: Digestive enzymes catalyze the hydrolysis of bonds in food molecules. Function: Protection against disease Example: Antibodies inactivate and help destroy viruses and bacteria. Enzyme Antibodies Bacterium Virus Storage proteins Transport proteins Function: Storage of amino acids Examples: 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: Transport of substances Examples: 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. Ovalbumin Transport protein Amino acids for embryo Cell membrane Hormonal proteins Receptor proteins Function: Coordination of an organism‘s activities Example: Insulin, a hormone secreted by the pancreas, causes other tissues to take up glucose, thus regulating blood sugar concentration. Function: Response of cell to chemical stimuli Example: Receptors built into the membrane of a nerve cell detect signaling molecules released by other nerve cells. Receptor protein Insulin secreted High blood sugar Normal blood sugar Signaling molecules Contractile and motor proteins Structural proteins Function: Movement Examples: Motor proteins are responsible for the undulations of cilia and flagella. Actin and myosin proteins are responsible for the contraction of muscles. 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. Actin Myosin Collagen Muscle tissue 30 om hydrogen atom, or it may be a carbon skeleton with various functional groups attached. 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. Figure 5.14 shows 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 amino acids are grouped according to the properties of their side chains. One group consists of amino acids with nonpolar side chains, 76 UNIT ONE The Chemistry of Life Connective tissue 60 om which are hydrophobic. Another group consists of amino acids with polar side chains, which are hydrophilic. Acidic amino acids have side chains that are generally negative in charge due to the presence of a carboxyl group, which is usually dissociated (ionized) at cellular pH. Basic amino acids have amino groups in their side chains that are generally positive in charge. (The terms acidic and basic in this context refer only to groups in the side chains because all amino acids—as monomers—have carboxyl groups and amino groups.) Because they are charged, acidic and basic side chains are also hydrophilic. . Figure 5.14 The 20 amino acids of proteins. At the top right are the non-ionized and ionized forms of a generic amino acid. The specific amino acids are shown below in their ionized form, prevalent at the pH within a cell (pH 7.2). The amino acids are grouped by properties of their side chains. The three-letter and one-letter abbreviations for the amino acids are in parentheses. All of the amino acids used in proteins are L enantiomers (see Figure 4.7c). Side chain (R group) N H C OH H Carboxyl group Nonpolar side chains; hydrophobic CH3 H H3N+ C C H O O– H3N+ Glycine (Gly or G) C C H O O– C – OH H Amino group Carboxyl group CH3 CH3 CH3 CH CH2 CH CH2 C C H O O– H3N+ Valine (Val or V) CH H3C C C H O O– Ionized generic amino acid C CH3 CH3 H3N+ Alanine (Ala or A) c carbon O H H N+ H C Amino group Side chain (R group) R O H Non-ionized generic amino acid Side chain (R group) c carbon R H3N+ C C H O O– Isoleucine (Ile or I) Leucine (Leu or L) CH3 S NH CH2 CH2 H3 N+ CH2 C C H O O– H3N+ Methionine (Met or M) CH2 H2C CH2 C C H O O– H3 N+ C C H O Phenylalanine (Phe or F) Tryptophan (Trp or W) Since cysteine is only weakly polar, it is sometimes classified as a nonpolar amino acid. OH O– H2 CH2 N+ C C H O O– Proline (Pro or P) Polar side chains; hydrophilic OH CH2 H3N+ O– C C H O H3N+ Serine (Ser or S) C C H O NH2 O C SH OH CH3 CH CH2 O– H3N+ Threonine (Thr or T) C H O O– H3N+ Cysteine (Cys or C) C C H O O– H3N+ Tyrosine (Tyr or Y) Electrically charged side chains; hydrophilic CH2 CH2 CH2 C NH2 O C CH2 C C H O O– H3N+ Asparagine (Asn or N) C C H O O– Glutamine (Gln or Q) Basic (positively charged) NH2 Acidic (negatively charged) NH3 C CH2 NH C CH2 CH2 C CH2 CH2 CH2 CH2 CH2 CH2 CH2 O– O– H3N+ + O C C H O Aspartic acid (Asp or D) O– H3N+ O C C H O Glutamic acid (Glu or E) O– H3N+ C C H O Lysine (Lys or K) CHAPTER 5 O– H3N+ NH2+ NH+ NH CH2 C C H O Arginine (Arg or R) O– H3N+ C C H O O– Histidine (His or H) The Structure and Function of Large Biological Molecules 77 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 adjacent to the amino group of the other, they can become joined by a dehydration reaction, with the removal of a water molecule. 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. You’ll learn more about how cells synthesize polypeptides in Concept 17.4. 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 1,000 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 (the N-terminus of the polypeptide), while the opposite end has a free carboxyl . 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. CH3 OH S CH2 SH CH2 CH2 H H N CH2 H C C H O N H C C H O OH N H C C H O OH Peptide bond H2O CH3 Side chains (R groups) OH S CH2 SH CH2 CH2 Backbone New peptide bond forming H H N CH2 H C C H O Amino end (N-terminus) N H C C H O N Peptide bond C C H O OH Carboxyl end (C-terminus) DRAW IT Label 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. 78 UNIT ONE The Chemistry of Life group (the C-terminus). The chemical nature of the molecule as a whole is determined by the kind and sequence of the side chains, which determine how a polypeptide folds and thus its final shape and chemical characteristics. 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 monomers into diverse sequences. Protein Structure and Function The specific activities of proteins result from their intricate three-dimensional architecture, the simplest level of which is the sequence of their amino acids. What can the amino acid sequence of a polypeptide tell us about the three-dimensional structure (commonly referred to simply as the “structure”) of the protein and its function? The term polypeptide is not synonymous with the term protein. Even for a protein consisting of a single polypeptide, the relationship is somewhat analogous to that between a long strand of yarn and a sweater of particular size and shape that can be knitted from the yarn. A functional protein is not just a 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 formation of various bonds between parts of the chain, which in turn depends on the sequence of amino acids. Many proteins 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 function, Figure 5.17 shows the exact match of shape between 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. Also, you may recall another example of molecules with matching shapes from Concept 2.3: endorphin molecules (produced by the body) and morphine molecules (a manufactured drug), both of which fit into 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 have a shape similar to that of endorphins and can thus fit into and bind to endorphin receptors in the brain. This fit is very specific, something like a handshake (see Figure 2.16). The endorphin receptor, like other receptor molecules, is a protein. The function of a protein—for instance, the ability of a receptor protein to bind to a particular pain-relieving signaling molecule—is an emergent property resulting from exquisite molecular order. . Figure 5.16 VISUALIZING PROTEINS Proteins can be represented in different ways, depending on the goal of the illustration. Target molecule Structural Models Using data from structural studies of proteins, computers can generate various types of models. Each model emphasizes a different aspect of the protein’s structure, but no model can show what a protein actually looks like. These three models depict lysozyme, a protein in tears and saliva that helps prevent infection by binding to target molecules on bacteria. 1. In which model is it easiest to follow the polypeptide backbone? Instructors: The tutorial “Molecular Model: Lysozyme,” in which students rotate 3-D models of lysozyme, can be assigned in Mastering Biology. Space-filling model: Emphasizes the overall globular shape. Shows all the atoms of the protein (except hydrogen), which are color-coded: gray = carbon, red = oxygen, blue = nitrogen, and yellow = sulfur. Ribbon model: Shows only the polypeptide backbone, emphasizing how it folds and coils to form a 3-D shape, in this case stabilized by disulfide bridges (yellow lines). Simplified Diagrams It isn‘t always necessary to use a detailed computer model; simplified diagrams are useful when the focus of the figure is on the function of the protein, not the structure. Instructors: Additional questions related to this Visualizing Figure can be assigned in Mastering Biology. Wireframe model (blue): Shows the polypeptide backbone with side chains extending from it. A ribbon model (purple) is superimposed on the wireframe model. The bacterial target molecule (yellow) is bound. Pancreas cell secreting insulin Enzyme A transparent shape is drawn around the contours of a ribbon model of the protein rhodopsin, showing the shape of the molecule as well as some internal details. When structural details are not needed, a solid shape can be used. A simple shape is used here to represent a generic enzyme because the diagram focuses on enzyme action in general. 2. Draw a simple version of lysozyme that shows its overall shape, based on the molecular models in the top section of the figure. Antibody protein Sometimes a protein is represented simply as a dot, as shown here for insulin. 3. Why is it unnecessary to show the actual shape of insulin here? Protein from flu virus c Figure 5.17 Complementarity of shape between two protein surfaces. 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 (yellow and green, right). This is a wireframe model modified by adding an “electron density map” in the region where the two proteins meet. Computer software was then used to back the images away from each other slightly. Four Levels of Protein Structure In spite of their great diversity, proteins share three superimposed levels of structure, known as primary, secondary, and tertiary structure. A fourth level, quaternary structure, arises when a protein consists of two or more polypeptide chains. Figure 5.18 describes these four levels of protein structure. Be sure to study this figure thoroughly before going on to the next section. VISUAL SKILLS What do these computer models allow you to see Mastering Biology Animation: Protein Structure about the two proteins? CHAPTER 5 The Structure and Function of Large Biological Molecules 79 Exploring Levels of Protein Structure . Figure 5.18 Primary Structure Secondary Structure Linear chain of amino acids Regions stabilized by hydrogen bonds between atoms of the polypeptide backbone The primary structure of 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. 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. H Amino acids H O + H N H Amino end R C C C N R H +H 3N H N H C C O R C Gly Pro Thr Gly Thr Gly Glu Ser Lys Cys 1 5 10 25 Leu Met 15 20 Val His Val Ala Val Asn Ile Ala Pro Ser Gly Arg Val Ala Asp Leu Val Lys Val d strands (orange), which together will form a d pleated sheet Phe Arg 35 Lys 40 45 50 Ala Ala Asp Asp Thr Trp Glu Pro Phe Ala Ser Gly Lys Thr Ser Glu Ser Gly Glu 70 65 55 60 Ile Glu Val Lys Tyr Ile Gly Glu Val Phe Glu Glu Glu Thr Thr Leu Gly Asp Thr 80 Ser 85 90 Tyr Trp Lys Ala Leu Gly Ile Ser Pro Phe His Glu His Ala Glu Val Val Phe 95 115 Tyr Leu His Blue region will coil into an c helix 75 Lys 110 105 100 Ser Tyr Pro Ser Leu Leu Ala Ala Ile Thr Tyr Arg Arg Pro Gly Ser Asp Thr Ala Asn Ser Thr Thr 120 125 Ala Val Val Thr Asn Pro Lys Glu O C Carboxyl end O– The primary structure is like the order of letters in a very long word. If left to chance, there would be 20127 different 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 information. The primary structure in turn dictates secondary structure (c helices and d pleated sheets) and tertiary structure, due to the chemical nature of the backbone and the side chains (R groups) of the amino acids along the polypeptide. 80 UNIT ONE The Chemistry of Life d strand, often shown as a folded or flat arrow pointing toward the carboxyl end Hydrogen bond Pro Primary structure of transthyretin 30 Hydrogen bond A region of d pleated sheet (made up of adjacent d strands) in transthyretin O H A region of c helix in transthyretin 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 repeating 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 hydrogen bonds are weak, but because they are repeated many times 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 c helix, a delicate coil held together by hydrogen bonding between every fourth amino acid, as shown above. Although each transthyretin polypeptide has only one c helix region (see the Primary and Tertiary Structure sections), other globular proteins have multiple stretches of c helix separated by nonhelical regions (see hemoglobin in the Quaternary Structure section). Some fibrous proteins, such as c-keratin, the structural protein of hair, have the c helix formation over most of their length. The other secondary structure is the d pleated sheet. As shown above, two or more segments of the polypeptide chain lying side by side (called d strands) are connected by hydrogen bonds between parts of the two parallel segments. d pleated sheets make up the core of many globular proteins, as is the case for transthyretin (see Tertiary Structure), and dominate some fibrous proteins, including 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. c Spiders secrete silk fibers made of a structural protein containing d pleated sheets, which allow the spiderweb to stretch