The Structure and Function of Large Biological Molecules PDF

The Structure and Function of Large Biological Molecules 5 Figure 5.1 Why is the structure of a protein important for its function? KEY CONCEPTS The Molecules of Life...

The Structure and Function of Large Biological Molecules 5 Figure 5.1 Why is the structure of a protein important for its function? KEY CONCEPTS The Molecules of Life Given the rich complexity of life on Earth, it might surprise you that the most 5.1 Macromolecules are polymers, built from monomers 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 5.2 Carbohydrates serve as fuel acids. On the molecular scale, members of three of these classes—carbohydrates, and building material proteins, and nucleic acids—are huge and are therefore called macromolecules. 5.3 Lipids are a diverse group of For example, a protein may consist of thousands of atoms that form a molecular hydrophobic molecules colossus with a mass well over 100,000 daltons. Considering the size and complexity 5.4 Proteins include a diversity of of macromolecules, it is noteworthy that biochemists have determined the detailed structures, resulting in a wide structure of so many of them. The image in Figure 5.1 is a molecular model of a range of functions protein called alcohol dehydrogenase, which breaks down alcohol in the body. 5.5 Nucleic acids store, transmit, The architecture of a large biological molecule plays an essential role in its and help express hereditary function. Like water and simple organic molecules, large biological molecules information exhibit unique emergent properties arising from the orderly arrangement of their 5.6 Genomics and proteomics have atoms. In this chapter, we’ll first consider how macromolecules are built. Then transformed biological inquiry we’ll examine the structure and function of all four classes of large biological and applications molecules: carbohydrates, lipids, proteins, and nucleic acids. The scientist in the foreground is using 3-D glasses to help her visualize the structure of the protein displayed on her screen. When you see this blue icon, log in to MasteringBiology Get Ready for This Chapter and go to the Study Area for digital resources. 66 CONCEPT 5.1 Figure 5.2 The synthesis and breakdown of polymers. (a) Dehydration reaction: synthesizing a polymer Macromolecules are polymers, built from monomers HO 1 2 3 H HO H Large carbohydrates, proteins, and nucleic acids are chain- Short polymer Unlinked monomer like molecules called polymers (from the Greek polys, many, Dehydration removes a water and meros, part). A polymer is a long molecule consisting of molecule, forming a new bond. H 2O many similar or identical building blocks linked by covalent bonds, much as a train consists of a chain of cars. The repeat- ing units that serve as the building blocks of a polymer are HO 1 2 3 4 H smaller molecules called monomers (from the Greek monos, single). In addition to forming polymers, some monomers Longer polymer have functions of their own. (b) Hydrolysis: breaking down a polymer The Synthesis and Breakdown of Polymers HO 1 2 3 4 H Although each class of polymer is made up of a different type of monomer, the chemical mechanisms by which cells H2O make and break down polymers are basically the same in all Hydrolysis adds a water molecule, breaking a bond. cases. In cells, these processes are facilitated by enzymes, specialized macromolecules that speed up chemical reac- tions. The reaction connecting monomers is a good example HO 1 2 3 H HO H of a dehydration reaction, a reaction in which two mol- ecules are covalently bonded to each other with the loss of a water molecule (Figure 5.2a). When a bond forms between Animation: Making and Breaking Polymers two monomers, each monomer contributes part of the water molecule that is released during the reaction: One monomer differences between close relatives, such as human siblings, provides a hydroxyl group ( ¬ OH), while the other provides reflect small variations in polymers, particularly DNA and a hydrogen ( ¬ H). This reaction is repeated as monomers proteins. Molecular differences between unrelated individu- are added to the chain one by one, making a polymer (also als are more extensive, and those between species greater still. called polymerization). The diversity of macromolecules in the living world is vast, Polymers are disassembled to monomers by hydrolysis, and the possible variety is effectively limitless. a process that is essentially the reverse of the dehydration reac- What is the basis for such diversity in life’s polymers? tion (Figure 5.2b). Hydrolysis means water breakage (from These molecules are constructed from only 40 to 50 com- the Greek hydro, water, and lysis, break). The bond between mon monomers and some others that occur rarely. Building monomers is broken by the addition of a water molecule, a huge variety of polymers from such a limited number of with a hydrogen from water attaching to one monomer and monomers is analogous to constructing hundreds of thou- the hydroxyl group attaching to the other. An example of sands of words from only 26 letters of the alphabet. The key hydrolysis within our bodies is the process of digestion. The is arrangement—the particular linear sequence that the units bulk of the organic material in our food is in the form of poly- follow. However, this analogy falls far short of describing the mers that are much too large to enter our cells. Within the great diversity of macromolecules because most biological digestive tract, various enzymes attack the polymers, speeding polymers have many more monomers than the number of up hydrolysis. Released monomers are then absorbed into the letters in even the longest word. Proteins, for example, are bloodstream for distribution to all body cells. Those cells can built from 20 kinds of amino acids arranged in chains that then use dehydration reactions to assemble the monomers are typically hundreds of amino acids long. The molecular into new, different polymers that can perform specific func- logic of life is simple but elegant: Small molecules common tions required by the cell. (Dehydration reactions and hydro- to all organisms act as building blocks that are ordered into lysis can also be involved in the formation and breakdown of unique macromolecules. molecules that are not polymers, such as some lipids.) Despite this immense diversity, molecular structure and function can still be grouped roughly by class. Let’s examine The Diversity of Polymers each of the four major classes of large biological molecules. A cell has thousands of different macromolecules; the col- For each class, the large molecules have emergent properties lection varies from one type of cell to another. The inherited not found in their individual components. CHAPTER 5 The Structure and Function of Large Biological Molecules 67 CONCEPT CHECK 5.1 Figure 5.3 The structure and classification of some monosaccharides. Sugars vary in the location of their carbonyl 1. What are the four main classes of large biological groups (orange), the length of their carbon skeletons, and the way molecules? Which class does not consist of polymers? their parts are arranged spatially around asymmetric carbons (compare, 2. How many molecules of water are needed to completely for example, the purple portions of glucose and galactose). hydrolyze a polymer that is ten monomers long? 3. WHAT IF? If you eat a piece of fish, what reactions Aldoses (Aldehyde Sugars) Ketoses (Ketone Sugars) must occur for the amino acid monomers in the protein Carbonyl group at end of Carbonyl group within of the fish to be converted to new proteins in your body? carbon skeleton carbon skeleton For suggested answers, see Appendix A. Trioses: three-carbon sugars (C3H6O3) CONCEPT 5.2 H O H C H C OH Carbohydrates serve as fuel C O H C OH and building material H C OH H C OH Carbohydrates include sugars and polymers of sugars. The H H simplest carbohydrates are the monosaccharides, or simple Glyceraldehyde Dihydroxyacetone sugars; these are the monomers from which more complex An initial breakdown An initial breakdown carbohydrates are built. Disaccharides are double sugars, con- product of glucose product of glucose sisting of two monosaccharides joined by a covalent bond. Pentoses: five-carbon sugars (C5H10O5) Carbohydrate macromolecules are polymers called polysac- charides, composed of many sugar building blocks. H H O Animation: Carbohydrates C H C OH H C OH C O Sugars H C OH H C OH Monosaccharides (from the Greek monos, single, and sacchar, H C OH H C OH sugar) generally have molecular formulas that are some mul- tiple of the unit CH2O. Glucose (C6H12O6), the most common H C OH H C OH monosaccharide, is of central importance in the chemistry H H of life. In the structure of glucose, we can see the trademarks Ribose Ribulose of a sugar: The molecule has a carbonyl group, l C “ O, and A component of RNA An intermediate √ in photosynthesis multiple hydroxyl groups, ¬ OH (Figure 5.3). Depending on the location of the carbonyl group, a sugar is either an Hexoses: six-carbon sugars (C6H12O6) aldose (aldehyde sugar) or a ketose (ketone sugar). Glucose, for example, is an aldose; fructose, an isomer of glucose, is a H H O H O ketose. (Most names for sugars end in -ose.) Another criterion C C H C OH for classifying sugars is the size of the carbon skeleton, which ranges from three to seven carbons long. Glucose, fructose, H C OH H C OH C O and other sugars that have six carbons are called hexoses. HO C H HO C H HO C H Trioses (three-carbon sugars) and pentoses (five-carbon sug- H C OH HO C H H C OH ars) are also common. H C OH H C OH H C OH Still another source of diversity for simple sugars is in the way their parts are arranged spatially around asymmet- H C OH H C OH H C OH ric carbons. (Recall that an asymmetric carbon is a carbon H H H attached to four different atoms or groups of atoms.) Glucose Glucose Galactose Fructose and galactose, for example, differ only in the placement of Energy sources for organisms An energy source for organisms parts around one asymmetric carbon (see the purple boxes in Figure 5.3). What seems like a small difference is significant MAKE CONNECTIONS In the 1970s, a process was developed that enough to give the two sugars distinctive shapes and binding converts the glucose in corn syrup to its sweeter-tasting isomer, fructose. activities, thus different behaviors. 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 Although it is convenient to draw glucose with a linear car- and fructose? (See Figure 4.7.) bon skeleton, this representation is not completely accurate. In aqueous solutions, glucose molecules, as well as most other Animation: Monosaccharides 68 UNIT ONE The Chemistry of Life  Figure 5.4 Linear and ring forms of glucose. H O 1C 6 CH2OH 6 CH2OH CH2OH 2 6 H C OH 5C O H 5C O O H H H H 5 H 3 H H HO C H H H 4 1 4C 1C 4C 1C OH H H 4 C OH OH H OH H HO 3 2 OH O OH 2 OH 2 OH 5 3C C 3C C H OH H C OH 6 H OH H OH (b) Abbreviated ring structure. Each H C OH unlabeled corner represents a H carbon. The ring’s thicker edge indicates that you are looking at the (a) Linear and ring forms. Chemical equilibrium between the linear and ring structures greatly favors ring edge-on; the components the formation of rings. The carbons of the sugar are numbered 1 to 6, as shown. To form the attached to the ring lie above or glucose ring, carbon 1 (magenta) bonds to the oxygen (blue) attached to carbon 5. below the plane of the ring. 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 fructose and glucose rings. five- and six-carbon sugars, form rings, because they are are generally incorporated as monomers into disaccharides or the most stable form of these sugars under physiological polysaccharides, discussed next. conditions (Figure 5.4). A disaccharide consists of two monosaccharides joined Monosaccharides, particularly glucose, are major nutrients by a glycosidic linkage, a covalent bond formed between for cells. In the process known as cellular respiration, cells two monosaccharides by a dehydration reaction (glyco refers to extract energy from glucose molecules by breaking them carbohydrate). For example, maltose is a disaccharide formed down in a series of reactions. Not only are simple-sugar mole- by the linking of two molecules of glucose (Figure 5.5a). Also cules a major fuel for cellular work, but their carbon skeletons known as malt sugar, maltose is an ingredient used in brew- also serve as raw material for the synthesis of other types of ing beer. The most prevalent disaccharide is sucrose, or table small organic molecules, such as amino acids and fatty acids. sugar. Its two monomers are glucose and fructose (Figure 5.5b). Sugar molecules that are not immediately used in these ways Plants generally transport carbohydrates from leaves to roots Figure 5.5 Examples of disaccharide synthesis. (a) Dehydration reaction in the synthesis of maltose. CH2OH CH2OH CH2OH CH2OH 1– 4 The bonding of two glucose H O H H O H H O H glycosidic H O H units forms maltose. The 1–4 H H H 1 linkage 4 H glycosidic linkage joins the OH H OH H OH H OH H number 1 carbon of one HO OH HO OH HO O OH glucose to the number 4 carbon of the second glucose. H OH H OH H OH H OH Joining the glucose monomers H2O in a different way would re- Glucose Glucose Maltose sult in a different disaccharide. (b) Dehydration reaction in CH2OH CH2OH the synthesis of sucrose. CH2OH 1– 2 CH2OH Sucrose is a disaccharide H O H O H H O H glycosidic O H formed from glucose and H H 1 linkage 2 fructose. Notice that OH H H HO OH H H HO HO OH HO fructose forms a five-sided CH2OH HO O CH2OH ring, though it is a hexose like glucose. H OH OH H H OH OH H H2O Glucose Fructose Sucrose DRAW IT Referring to Figures 5.3 and 5.4, number the carbons in each sugar Animation: Synthesis of Sucrose in this figure. How does the name of each linkage relate to the numbers? CHAPTER 5 The Structure and Function of Large Biological Molecules 69 and other nonphotosynthetic organs in the form of sucrose. glycosidic linkages. Some polysaccharides serve as storage Lactose, the sugar present in milk, is another disaccharide, in material, hydrolyzed as needed to provide sugar for cells. this case a glucose molecule joined to a galactose molecule. Other polysaccharides serve as building material for structures Disaccharides must be broken down into monosaccharides that protect the cell or the whole organism. The architecture to be used for energy by organisms. Lactose intolerance is a and function of a polysaccharide are determined by its sugar common condition in humans who lack lactase, the enzyme monomers and by the positions of its glycosidic linkages. that breaks down lactose. The sugar is instead broken down by intestinal bacteria, causing formation of gas and subsequent Storage Polysaccharides cramping. The problem may be avoided by taking the enzyme Both plants and animals store sugars for later use in the form lactase when eating or drinking dairy products or consuming of storage polysaccharides (Figure 5.6). Plants store starch, dairy products that have already been treated with lactase to a polymer of glucose monomers, as granules within cellular break down the lactose. structures known as plastids. (Plastids include chloroplasts.) Synthesizing starch enables the plant to stockpile surplus glu- Polysaccharides cose. Because glucose is a major cellular fuel, starch represents Polysaccharides are macromolecules, polymers with a stored energy. The sugar can later be withdrawn by the plant few hundred to a few thousand monosaccharides joined by from this carbohydrate “bank” by hydrolysis, which breaks the 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 molecules. There are two kinds of starch: amylose and amylopectin. Cellulose, with a different kind of glucose linkage, is always unbranched. Storage structures (plastids) Amylose (unbranched) containing starch granules in a potato tuber cell O O O O O O O O O O O O O O O O Glucose Amylopectin monomer (somewhat branched) O O O O 50 μm O O O O O O O O O (a) Starch O O Muscle O tissue Glycogen granules Glycogen (extensively branched) stored in muscle O tissue O O O O O O O O O O O O O O O O O O O Cell wall O 1 μm O O (b) Glycogen Cellulose microfibrils in a plant cell wall Cellulose molecule (unbranched) Plant cell, surrounded 10 μm Microfibril (bundle of O O by cell wall about 80 cellulose O O O OH Hydrogen bonds between molecules) parallel cellulose molecules O O hold them together. O O O OH 0.5 μm O O O O O O O O O O O O O O (c) Cellulose 70 UNIT ONE The Chemistry of Life bonds between the glucose monomers. Most animals, including The difference is based on the fact that there are actually two humans, also have enzymes that can hydrolyze plant starch, slightly different ring structures for glucose (Figure 5.7a). making glucose available as a nutrient for cells. Potato tubers When glucose forms a ring, the hydroxyl group attached to and grains—the fruits of wheat, maize (corn), rice, and other the number 1 carbon is positioned either below or above the grasses—are the major sources of starch in the human diet. plane of the ring. These two ring forms for glucose are called Most of the glucose monomers in starch are joined by 1–4 alpha (α) and beta (β), respectively. (Greek letters are often linkages (number 1 carbon to number 4 carbon), like the glu- used as a “numbering” system for different versions of bio- cose units in maltose (see Figure 5.5a). The simplest form of logical structures, much as we use the letters a, b, c, and so on starch, amylose, is unbranched. Amylopectin, a more complex for the parts of a question or a figure.) In starch, all the glu- starch, is a branched polymer with 1–6 linkages at the branch cose monomers are in the α configuration (Figure 5.7b), the points. Both of these starches are shown in Figure 5.6a. arrangement we saw in Figures 5.4 and 5.5. In contrast, the Animals store a polysaccharide called glycogen, a poly- glucose monomers of cellulose are all in the β configuration, mer of glucose that is like amylopectin but more extensively making every glucose monomer “upside down” with respect branched (Figure 5.6b). Vertebrates store glycogen mainly to its neighbors (Figure 5.7c; see also Figure 5.6c). in liver and muscle cells. Hydrolysis of glycogen in these cells The differing glycosidic linkages in starch and cellulose releases glucose when the demand for sugar increases. (The give the two molecules distinct three-dimensional shapes. extensively branched structure of glycogen fits its function: Certain starch molecules are largely helical, fitting their More free ends are available for hydrolysis.) This stored fuel function of efficiently storing glucose units. Conversely, a cannot sustain an animal for long, however. In humans, for cellulose molecule is straight. Cellulose is never branched, example, glycogen stores are depleted in about a day unless and some hydroxyl groups on its glucose monomers are free they are replenished by eating. This is an issue of concern in low- to hydrogen-bond with the hydroxyls of other cellulose mol- carbohydrate diets, which can result in weakness and fatigue. ecules lying parallel to it. In plant cell walls, parallel cellulose molecules held together in this way are grouped into units Structural Polysaccharides called microfibrils (see Figure 5.6c). These cable-like microfi- Organisms build strong materials from structural polysac- brils are a strong building material for plants and an impor- charides. For example, the polysaccharide called cellulose tant substance for humans because cellulose is the major is a major component of the tough walls that enclose plant constituent of paper and the only component of cotton. cells (Figure 5.6c). Globally, plants produce almost 1014 kg The unbranched structure of cellulose thus fits its function: (100 billion tons) of cellulose per year; it is the most abundant imparting strength to parts of the plant. organic compound on Earth. Enzymes that digest starch by hydrolyzing its α link- Like starch, cellulose is a polymer of glucose with 1–4 gly- ages are unable to hydrolyze the β linkages of cellulose cosidic linkages, but the linkages in these two polymers differ. due to the different shapes of these two molecules. In fact, Figure 5.7 Starch and cellulose structures. H O (a) α and β glucose ring C structures. These two CH2OH CH2OH interconvertible forms of O H C OH O H H H OH glucose differ in the H H 4 1 HO C H 4 1 placement of the hydroxyl OH H OH H group (highlighted in blue) HO OH H C OH HO H attached to the number 1 carbon. H OH H C OH H OH α Glucose H C OH β Glucose H CH2OH CH2OH CH2OH CH2OH CH2OH OH CH2OH OH O O O O O O 1 4 O OH O OH OH O OH O OH O OH OH 1 4 O OH HO OH HO OH O O OH OH OH OH OH CH2OH OH CH2OH (b) Starch: 1–4 linkage of α glucose monomers. All monomers (c) Cellulose: 1–4 linkage of β glucose monomers. In cellulose, are in the same orientation. Compare the positions of the every β glucose monomer is upside down with respect to its OH groups highlighted in yellow with those in cellulose (c). neighbors. (See the highlighted OH groups.) Animation: Starch, Cellulose, and Glycogen Structures CHAPTER 5 The Structure and Function of Large Biological Molecules 71  Figure 5.8 Chitin, a structural polysaccharide. CONCEPT CHECK 5.2 1. Write the formula for a monosaccharide that has three CH2OH ◀ The structure carbons. O of the chitin H OH monomer 2. A dehydration reaction joins two glucose molecules to H form maltose. The formula for glucose is C6H12O6. What is OH H OH H the formula for maltose? 3. WHAT IF? After a cow is given antibiotics to treat an H NH infection, a vet gives the animal a drink of “gut culture” containing various prokaryotes. Why is this necessary? C O For suggested answers, see Appendix A. CH3 CONCEPT 5.3 ◀ Chitin, embedded in proteins, forms the exoskeleton of arthropods. This Lipids are a diverse group emperor dragonfly (Anax imperator) is of hydrophobic molecules molting—shedding its old exoskeleton (brown) and emerging upside down in adult form. 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 com- pounds called lipids are grouped with each other because few organisms possess enzymes that can digest cellulose. they share one important trait: They mix poorly, if at all, Almost all animals, including humans, do not; the cellulose with water. The hydrophobic behavior of lipids is based on in our food passes through the digestive tract and is elimi- their molecular structure. Although they may have some nated with the feces. Along the way, the cellulose abrades polar bonds associated with oxygen, lipids consist mostly of the wall of the digestive tract and stimulates the lining to hydrocarbon regions. Lipids are varied in form and function. secrete mucus, which aids in the smooth passage of food They include waxes and certain pigments, but we will focus through the tract. Thus, although cellulose is not a nutrient on the types of lipids that are most important biologically: for humans, it is an important part of a healthful diet. Most fats, phospholipids, and steroids. fruits, vegetables, and whole grains are rich in cellulose. On food packages, “insoluble fiber” refers mainly to cellulose. Animation: Lipids Some microorganisms can digest cellulose, breaking it down into glucose monomers. A cow harbors cellulose- Fats digesting prokaryotes and protists in its gut. These microbes Although fats are not polymers, they are large molecules assem- hydrolyze the cellulose of hay and grass and convert the glu- bled from smaller molecules by dehydration reactions, like cose to other compounds that nourish the cow. Similarly, a the dehydration reaction described for the polymerization of termite, which is unable to digest cellulose by itself, has pro- monomers in Figure 5.2a. A fat is constructed from two kinds karyotes or protists living in its gut that can make a meal of of smaller molecules: glycerol and fatty acids (Figure 5.9a). wood. Some fungi can also digest cellulose in soil and else- Glycerol is an alcohol; each of its three carbons bears a hydroxyl where, thereby helping recycle chemical elements within group. A fatty acid has a long carbon skeleton, usually 16 or Earth’s ecosystems. 18 carbon atoms in length. The carbon at one end of the skel- Another important structural polysaccharide is chitin, eton is part of a carboxyl group, the functional group that gives the carbohydrate used by arthropods (insects, spiders, crus- these molecules the name fatty acid. The rest of the skeleton taceans, and related animals) to build their exoskeletons consists of a hydrocarbon chain. The relatively nonpolar C ¬ H (Figure 5.8). An exoskeleton is a hard case that surrounds bonds in the hydrocarbon chains of fatty acids are the reason the soft parts of an animal. Made up of chitin embedded in fats are hydrophobic. Fats separate from water because the a layer of proteins, the case is leathery and flexible at first, water molecules hydrogen-bond to one another and exclude but becomes hardened when the proteins are chemically the fats. This is why vegetable oil (a liquid fat) separates from linked to each other (as in insects) or encrusted with cal- the aqueous vinegar solution in a bottle of salad dressing. cium carbonate (as in crabs). Chitin is also found in fungi, In making a fat, three fatty acid molecules are each joined which use this polysaccharide rather than cellulose as the to glycerol by an ester linkage, a bond formed by a dehy- building material for their cell walls. Chitin is similar to dration reaction between a hydroxyl group and a carboxyl cellulose, with β linkages, except that the glucose mono- group. The resulting fat, also called a triacylglycerol, thus mer of chitin has a nitrogen-containing attachment consists of three fatty acids linked to one glycerol molecule. (see Figure 5.8). (Still another name for a fat is triglyceride, a word often found 72 UNIT ONE The Chemistry of Life  Figure 5.9 The synthesis and structure of a fat, Figure 5.10 Saturated and unsaturated fats and fatty acids. or triacylglycerol. The molecular building blocks of a fat are one molecule of glycerol and three molecules of fatty acids. (a) Saturated fat (a) One water molecule is removed for each fatty acid joined to the glycerol. (b) A fat molecule with three fatty acid units, two At room temperature, the molecules of a saturated fat, such as the fat in of them identical. The carbons of the fatty acids are arranged butter, are packed closely together, zigzag to suggest the actual orientations of the four single forming a solid. bonds extending from each carbon (see Figures 4.3a and 4.6b). H H H H H H H H H O H H H H H H H H Structural formula of a O H C OH C C C C C C C C C C C C C C C C H saturated fat molecule H C O C HO H H H H H H H (Each hydrocarbon chain O H H H H H H H H is represented as a zigzag H C O C H C OH line, where each bend H2O Fatty acid O represents a carbon atom; (in this case, palmitic acid) H C O C H C OH hydrogens are not H shown.) H Glycerol (a) One of three dehydration reactions in the synthesis of a fat Space-filling model of stearic acid, a saturated Ester linkage fatty acid (red = oxygen, black = carbon, gray = H O H H H H H H H hydrogen) H H H H H H H H H C O C C C C C C C C H C C C C C C C C H H H H H H H H H H H H H H H (b) Unsaturated fat O H H H H H H At room temperature, the molecules of H H H H H H H H C O C C C C C C C H an unsaturated fat such as olive oil C C C C C C C cannot pack together closely enough to H H H H H H H H H H H H H solidify because of the kinks in some of their fatty acid hydrocarbon chains. O H H H H H H H H H H H H H H H H C O C C C C C C C C H C C C C C C C C H H H H H H H H H H H H H H H H (b) Fat molecule (triacylglycerol) H O H C O C O Structural formula of an in the list of ingredients on packaged foods.) The fatty acids H C O C unsaturated fat molecule in a fat can all be the same, or they can be of two or three O different kinds, as in Figure 5.9b. H C O C The terms saturated fats and unsaturated fats are commonly H used in the context of nutrition (Figure 5.10). These terms refer to the structure of the hydrocarbon chains of the fatty Space-filling model of oleic acid, an unsaturated fatty acids. If there are no double bonds between carbon atoms acid 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 Cis double bond causes bending. 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 and butter—are solid at room temperature. In contrast, the chain wherever it occurs (Figure 5.10b). (See Figure 4.7b to fats of plants and fishes are generally unsaturated, meaning remind yourself about cis and trans double bonds.) that they are built of one or more types of unsaturated fatty A fat made from saturated fatty acids is called a saturated acids. Usually liquid at room temperature, plant and fish fats fat. Most animal fats are saturated: The hydrocarbon chains are referred to as oils—olive oil and cod liver oil are examples. of their fatty acids—the “tails” of the fat molecules—lack The kinks where the cis double bonds are located prevent the double bonds, and their flexibility allows the fat molecules molecules from packing together closely enough to solidify at to pack together tightly. Saturated animal fats—such as lard room temperature. The phrase “hydrogenated vegetable oils” CHAPTER 5 The Structure and Function of Large Biological Molecules 73 on food labels means that unsaturated fats have been syntheti- and other mammals stock their long-term food reserves in cally converted to saturated fats by adding hydrogen, allowing adipose cells (see Figure 4.6a), which swell and shrink as fat them to solidify. Peanut butter, margarine, and many other is deposited and withdrawn from storage. In addition to stor- products are hydrogenated to prevent lipids from separating ing energy, adipose tissue also cushions such vital organs as out in liquid (oil) form. the kidneys, and a layer of fat beneath the skin insulates the A diet rich in saturated fats is one of several factors that may body. This subcutaneous layer is especially thick in whales, contribute to the cardiovascular disease known as atheroscle- seals, and most other marine mammals, insulating their rosis. In this condition, deposits called plaques develop within bodies in cold ocean water. the walls of blood vessels, causing inward bulges that impede blood flow and reduce the resilience of the vessels. The pro- Phospholipids cess of hydrogenating vegetable oils produces not only satu- Cells as we know them could not exist without another rated fats but also unsaturated fats with trans double bonds. type of lipid—phospholipids. Phospholipids are essen- It appears that trans fats can contribute to coronary heart tial for cells because they are major constituents of cell disease (see Concept 42.4). Because trans fats are especially membranes. Their structure provides a classic example of common in baked goods and processed foods, the U.S. Food how form fits function at the molecular level. As shown in and Drug Administration (FDA) requires nutritional labels to Figure 5.11, a phospholipid is similar to a fat molecule include information on trans fat content. In addition, the FDA but has only two fatty acids attached to glycerol rather than has ordered trans fats to be removed from the U.S. food supply three. The third hydroxyl group of glycerol is joined to a by 2018. Some countries, such as Denmark and Switzerland, phosphate group, which has a negative electrical charge have already banned trans fats in foods. in the cell. Typically, an additional small charged or polar The major function of fats is energy storage. The hydro- molecule is also linked to the phosphate group. Choline carbon chains of fats are similar to gasoline molecules and is one such molecule (see Figure 5.11), but there are many just as rich in energy. A gram of fat stores more than twice as others as well, allowing formation of a variety of phospho- much energy as a gram of a polysaccharide, such as starch. lipids that differ from each other. Because plants are relatively immobile, they can function The two ends of phospholipids show different behaviors with bulky energy storage in the form of starch. (Vegetable with respect to water. The hydrocarbon tails are hydrophobic oils are generally obtained from seeds, where more compact and are excluded from water. However, the phosphate group storage is an asset to the plant.) Animals, however, must and its attachments form a hydrophilic head that has an affin- carry their energy stores with them, so there is an advantage ity for water. When phospholipids are added to water, they to having a more compact reservoir of fuel—fat. Humans self-assemble into a double-layered sheet called a “bilayer” + Figure 5.11 The structure of a phospholipid. A phospholipid CH2 N(CH3)3 Choline has a hydrophilic (polar) head and two hydrophobic (nonpolar) tails. Hydrophilic head CH2 This particular phospholipid, called a phosphatidylcholine, has a choline O attached to a phosphate group. Shown here are (a) the structural formula, O P O– Phosphate (b) the space-filling model (yellow = phosphorus, blue = nitrogen), O (c) the symbol for a phospholipid that will appear throughout this book, and (d) the bilayer structure formed by self-assembly of phospholipids CH2 CH CH2 Glycerol in an aqueous environment. O O DRAW IT Draw an oval around the hydrophilic head of the space-filling model. C O C O Figure Walkthrough Animation: Space-Filling Model of a Phospholipid Fatty acids Hydrophobic tails Kink due to cis double bond Hydrophilic head Hydrophobic tails (a) Structural formula (b) Space-filling model (c) Phospholipid symbol (d) Phospholipid bilayer 74 UNIT ONE The Chemistry of Life that shields their hydrophobic fatty acid tails from water (Figure 5.11d). CONCEPT 5.4 At the surface of a cell, phospholipids are arranged in a Proteins include a diversity of similar bilayer. The hydrophilic heads of the molecules are on the outside of the bilayer, in contact with the aqueous structures, resulting in a wide solutions inside and outside of the cell. The hydrophobic tails range of functions point toward the interior of the bilayer, away from the water. Nearly every dynamic function of a living being depends on The phospholipid bilayer forms a boundary between the cell proteins. In fact, the importance of proteins is underscored and its external environment and establishes separate com- by their name, which comes from the Greek word proteios, partments within eukaryotic cells; in fact, the existence of meaning “first,” or “primary.” Proteins account for more cells depends on the properties of phospholipids. than 50% of the dry mass of most cells, and they are instru- mental in almost everything organisms do. Some proteins Steroids speed up chemical reactions, while others play a role in Steroids are lipids characterized by a carbon skeleton defense, storage, transport, cellular communication, move- consisting of four fused rings. Different steroids are dis- ment, or structural support. Figure 5.13 shows examples tinguished by the particular chemical groups attached to of proteins with these functions, which you’ll learn more this ensemble of rings. Cholesterol, a type of steroid, is a about in later chapters. crucial molecule in animals (Figure 5.12). It is a common Life would not be possible without enzymes, most of component of animal cell membranes and is also the pre- which are proteins. Enzymatic proteins regulate metabo- cursor from which other steroids, such as the vertebrate sex lism by acting as catalysts, chemical agents that selec- hormones, are synthesized. In vertebrates, cholesterol is tively speed up chemical reactions without being consumed synthesized in the liver and is also obtained from the diet. in the reaction. Because an enzyme can perform its function A high level of cholesterol in the blood may contribute to over and over again, these molecules can be thought of as atherosclerosis, although some researchers are questioning workhorses that keep cells running by carrying out the the roles of cholesterol and saturated fats in the develop- processes of life. ment of this condition. A human has tens of thousands of different proteins, each with a specific structure and function; proteins, in fact, Figure 5.12 Cholesterol, a steroid. Cholesterol is the molecule are the most structurally sophisticated molecules known. from which other steroids, including the sex hormones, are synthesized. Consistent with their diverse functions, they vary extensively Steroids vary in the chemical groups attached to their four interconnected in structure, each type of protein having a unique three- rings (shown in gold). dimensional shape. H 3C CH3 Proteins are all constructed from the same set of 20 amino CH3 acids, linked in unbranched polymers. The bond between CH3 amino acids is called a peptide bond, so a polymer of amino CH3 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 three-dimensional structure. HO MAKE CONNECTIONS Compare cholesterol with the sex hormones shown in the figure at the beginning of Concept 4.3. Circle the chemical Amino Acid Monomers groups that cholesterol has in common with estradiol; put a square around the chemical groups that cholesterol has in common with testosterone. All amino acids share a common struc- Side chain (R group) ture. An amino acid is an organic R Interview with Lovell Jones: Investigating the effects of sex molecule with both an amino group hormones on cancer (see the interview before Chapter 2) α carbon and a carboxyl group (see Figure 4.9); H O the small figure shows the general for- CONCEPT CHECK 5.3 N C C mula for an amino acid. At the center H 1. Compare the structure of a fat (triglyceride) with that OH of the amino acid is an asymmetric H of a phospholipid. carbon atom called the alpha (α) Amino Carboxyl 2. Why are human sex hormones considered lipids? group group carbon. Its four different partners are an 3. WHAT IF? Suppose a membrane surrounded an oil droplet, as it does in the cells of plant seeds and in some amino group, a carboxyl group, a hydrogen atom, and a vari- animal cells. Describe and explain the form it might take. able group symbolized by R. The R group, also called the side For suggested answers, see Appendix A. chain, differs with each amino acid. CHAPTER 5 The Structure and Function of Large Biological Molecules 75  Figure 5.13 An overview of protein functions. Animation: Protein Functions Enzymatic proteins Defensive proteins Function: Selective acceleration of chemical reactions Function: Protection against disease Example: Digestive enzymes catalyze the hydrolysis of bonds in food Example: Antibodies inactivate and help destroy viruses and bacteria. molecules. Antibodies Enzyme Virus Bacterium Storage proteins Transport proteins Function: Storage of amino acids Function: Transport of substances Examples: Casein, the protein of milk, is the major source of amino Examples: Hemoglobin, the iron-containing protein of vertebrate acids for baby mammals. Plants have storage proteins in their seeds. blood, transports oxygen from the lungs to other parts of the body. Ovalbumin is the protein of egg white, used as an amino acid source Other proteins transport molecules across membranes, as shown here. for the developing embryo. Transport protein Ovalbumin Amino acids for embryo Cell membrane Hormonal proteins Receptor proteins Function: Coordination of an organism‘s activities Function: Response of cell to chemical stimuli Example: Insulin, a hormone secreted by the pancreas, causes other Example: Receptors built into the membrane of a nerve cell detect tissues to take up glucose, thus regulating blood sugar concentration. signaling molecules released by other nerve cells. Receptor protein Insulin High Normal Signaling molecules secreted blood sugar blood sugar Contractile and motor proteins Structural proteins Function: Movement Function: Support Examples: Motor proteins are responsible for the undulations of cilia Examples: Keratin is the protein of hair, horns, feathers, and other skin and flagella. Actin and myosin proteins are responsible for the contrac- appendages. Insects and spiders use silk fibers to make their cocoons tion of muscles. and webs, respectively. Collagen and elastin proteins provide a fibrous framework in animal connective tissues. Actin Myosin Collagen Muscle tissue 30 μm Connective tissue 60 μm Figure 5.14 shows the 20 amino acids that cells use to side chains. One group consists of amino acids with nonpolar build their thousands of proteins. Here the amino groups side chains, which are hydrophobic. Another group consists and carboxyl groups are all depicted in ionized form, the way of amino acids with polar side chains, which are hydrophilic. they usually exist at the pH found in a cell. The side chain Acidic amino acids have side chains that are generally negative (R group) may be as simple as a hydrogen atom, as in the in charge due to the presence of a carboxyl group, which is usu- amino acid glycine, or it may be a carbon skeleton with ally dissociated (ionized) at cellular pH. Basic amino acids have various functional groups attached, as in glutamine. amino groups in their side chains that are generally positive in The physical and chemical properties of the side chain deter- charge. (Notice that all amino acids have carboxyl groups and mine the unique characteristics of a particular amino acid, thus amino groups; the terms acidic and basic in this context refer affecting its functional role in a polypeptide. In Figure 5.14, only to groups in the side chains.) Because they are charged, the amino acids are grouped according to the properties of their acidic and basic side chains are also hydrophilic. 76 UNIT ONE The Chemistry of Life  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 L enantiomers (see Figure 4.7c). Nonpolar side chains; hydrophobic CH3 CH3 CH3 Side chain (R group) CH3 CH3 CH CH2 H CH3 CH CH2 H3C CH H3 N+ C C O– H3N+ C C O– H3 N+ C C O– H3 N+ C C O– H3N+ C C O– H O H O H O H O H O Glycine Alanine Valine Leucine Isoleucine (Gly or G) (Ala or A) (Val or V) (Leu or L) (Ile or I) CH3 S NH CH2 CH2 CH2 CH2 CH2 H2C CH2 H3N+ C C O– H3N+ C C O– H3N+ C C O– H2N+ C C O– H O H O H O H O Methionine Phenylalanine Tryptophan Proline (Met or M) (Phe or F) (Trp or W) (Pro or P) Polar side chains; hydrophilic Since cysteine is only weakly polar, it is sometimes classified OH NH2 O as a nonpolar amino acid. C NH2 O OH SH C CH2 OH CH3 CH2 CH CH2 CH2 CH2 CH2 H3N+ C C O– H3N+ C C O– H3N+ C C O– H3N+ C C O– H3N+ C C O– H3N+ C C O– H O H O H O H O H O H O Serine Threonine Cysteine Tyrosine Asparagine Glutamine (Ser or S) (Thr or T) (Cys or C) (Tyr or Y) (Asn or N) (Gln or Q) Electrically charged side chains; hydrophilic Basic (positively charged) NH2 Acidic (negatively charged) + NH3 C NH2+ O– O CH2 NH O– O C CH2 CH2 NH+ C CH2 CH2 CH2 NH CH2 CH2 CH2 CH2 CH2 H3N+ C C O– H3N+ C C O– H3N+ C C O– H3N+ C C O– H3N+ C C O– H O H O H O H O H O Aspartic acid Glutamic acid Lysine Arginine Histidine (Asp or D) (Glu or E) (Lys or K) (Arg or R) (His or H) CHAPTER 5 The Structure and Function of Large Biological Molecules 77 Polypeptides (Amino Acid Polymers) as a whole is determined by the kind and sequence of the side chains, which determine how a polypeptide folds and thus its Now that we have examined amino acids, let’s see how they are final shape and chemical characteristics. The immense variety linked to form polymers (Figure 5.15). When two amino acids of polypeptides in nature illustrates an important concept intro- are positioned so that the carboxyl group of one is adjacent duced earlier—that cells can make many different polymers by to the amino group of the other, they can become joined by a linking a limited set of monomers into diverse sequences. 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 Protein Structure and Function many amino acids linked by peptide bonds. You’ll learn more The specific activities of proteins result from their intricate about how cells synthesize polypeptides in Concept 17.4. three-dimensional architecture, the simplest level of which is The repeating sequence of atoms highlighted in purple in the sequence of their amino acids. What can the amino acid Figure 5.15 is called the polypeptide backbone. Extending from sequence of a polypeptide tell us about the three-dimensional this backbone are the different side chains (R groups) of the structure (commonly referred to simply as the “structure”) of amino acids. Polypeptides range in length from a few amino the protein and its function? The term polypeptide is not syn- acids to 1,000 or more. Each specific polypeptide has a unique onymous with the term protein. Even for a protein consisting of linear sequence of amino acids. Note that one end of the a single polypeptide, the relationship is somewhat analogous polypeptide chain has a free amino group (the N-terminus of to that between a long strand of yarn and a sweater of particular the polypeptide), while the opposite end has a free carboxyl size and shape that can be knitted from the yarn. A functional group (the C-terminus). The chemical nature of the molecule protein is not just a polypeptide chain, but one or more poly- Figure 5.15 Making a polypeptide chain. Peptide bonds are peptides precisely twisted, folded, and coiled into a molecule of formed by dehydration reactions, which link the carboxyl group of one unique shape, which can be shown in several different types of amino acid to the amino group of the next. The peptide bonds are models (Figure 5.16). And it is the amino acid sequence of each formed one at a time, starting with the amino acid at the amino end polypeptide that determines what three-dimensional structure (N-terminus). The polypeptide has a repetitive backbone (purple) to which the amino acid side chains (yellow and green) are attached. the protein will have under normal cellular conditions. When a cell synthesizes a polypeptide, t