The Structure and Function of Large Biological Molecules 1A Figure 5.1 Why do scientists study the structures of macromolecules? 5.1 Macromolecules are polymers, built from monomers Carbohydrates serve as fuel and building material Lipids are a diverse group of hydrophobic molecules Proteins include a diversity of structures, resulting in a wide range of functions Nucleic acids store, transmit, and help express hereditary information The Molecules of Given the rich complexity of life on Earth, we might expect organisms to have an enormous diversity of molecules. Re- ‘markably, however, the critically important large molecules of al living things—from bacteria to elephants—fall into just four main classes: carbohydrates, lipids, proteins, and nucleic ife 68° owsrone The Chemistry of Life acids. On the molecular scale, members of three of these lasses—carbohydrates, proteins, and nucleic acids—are huge and are therefore called macromolecules. For example, a protein may consist of thousands of atoms that form a mo- lecular colossus with a mass well over 100,000 daltons. Con sidering the size and complexity of macromolecules, it is noteworthy that biochemists have determined the detailed structure of so many of them. The scientist in the foreground ff Figure 5.1 is using 5-D glastes to help her visualize the structure of the protein displayed on her screen, ‘The architecture of a large biological molecule helps ex- plain how that molecule works. Like water and simple or ganic molecules, large biological molecules exhibit unique ‘emergent properties arising from the orderly arrangement of ‘their atoms. In this chapter, we'll fist consider how macto- molecules are built. Then we'll examine the structure and function of all four classes of large biological molecules: car- Dbohydrates, lipids, proteins, and nucleic acids concert 51 Macromolecules are polymers, built from monomers ‘The macromolecules in thuce of the four classes of life's or- ganic compounds—carbohydrates, proteins, and nucleic acids—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 cars. The repeating units that serve as the building blocks of a polymer are smaller molecules called monomers (Grom the Greek monos, single) serve as moniomers also have other functions of their own Some of the molecules that The Synthes Although each class of polymer is made up of a diferent type ‘of monomer, the chemical mechanisms by which cells make and break down polymers are basically the same in all cases. In cells, these processes ate facilitated by enzymes, specal- zed macromolecules that speed up chemical reactions Monomers are connected by a reaction in which two mol- ‘ecules are covalently bonded to each other, with the loss of a ‘water molecule; this is known as a dehydration reaction (Figure 5.28). When a bond forms between two monomers, ‘each monomer contributes part of the water molecule that is released during the reaction: One monomer provides a hydroxyl group (OH), while the other provides a hydrogen (CAD, This reaction is repeated as monomers are added to the chain one by one, making a polymer, Polymers ate disassembled to monomers by hydrolysis, a process that is essentially the reverse of the dehydration reac- and Breakdown of Polymers{a} Dehydration reaction: synthesizing a polymer Short polymer Unlinked! monomer Dehydration emoues 2 ater molecule, forming a new bond. Longer polymer (b) Hydrolysis: breaking down a polymer yaoi ade a water molecule, breaking a bond, tion (Figure 5.2b). Hydrolysis means to break using water (from the Greek hyulto, water, and Iysis, break). The bond be- ‘een the monomers is broken by the addition of a water mol- ecule, with the hydrogen from the water attaching to o: monomer and the hydroxyl group attaching to the adjacent ‘monomer, An example of hydrolysis working within our bod les isthe process of digestion. The bulk of the organic material, n ous 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. The released monomets are then absorbed into the bloodstream for dist. bution to all body cells. Those cells can then use dehydration reactions to assemble the monomers into new, different poly- ‘mers that can perform specific functions requited by the cell. The Diversity of Polymers Each cell has thousands of different macromolecules; the col. lection varies from one type of cell to another even in the same organism. ‘The inherent differences between. human siblings reflect small variations in polymers, particularly DNA. and proteins. Molecular differences between unrelated indi- viduals are more extensive and those between species greater stil, The diversity of macromolecules in the living world is ‘vast, and the possible varety is effectively Lnnitiess, What is the basis for such diversity in lfe's polymers? These molecules are constructed from only 40 to SO common monomers and some others that occur rarely. Building 2 ‘huge variety of polymers from such a limited number of ‘monomers is analogous to constructing hundreds of thou: sands of words from only 26 letters of the alphabet, The key {s 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 lewters in the longest word, Proteins, for example, are built rom 20 Kinds of amino acids arranged in chains that are typ- ically hundreds of amino acids long. The molecular logic of life is simple but elegant: Small molecules common to all or- anisms are ordered into unique macromolecules, Despite this immense diversity, molecular structure and function can still be grouped roughly by class. Le’s examine ‘each of the four major classes of large biological molecules, For each clas, the large molecules have emergent properties ‘not found in theie individual building blocks, cutee 5.1 1. What are the four main classes of large biologieal molecules? Which class does not consist of polymers? 2, How many molecules of water are needed to com- pletely hydrolyze a polymer thats ten monomers long? 3, MUTISMEEA Suppose you eat serving of fish, What reactions must occur forthe amino acid monomers fn the protein ofthe fsh tobe converted to new pro- teins in your body? For svgesed anor se Appendix A concert 5.2 Carbohydrates serve as fuel and building material Carbohydrates include both sugars and polymers of sugars, ‘The simplest carbohydrates are the monosaccharides, ot simple sugars; these ae the monomers from which more complex car- Dbohydrates are constructed, Disaccharides are double sugars, consisting of two monosaccharides joined by a covalent bond, ‘Carbohydrates also include macromolecules called polysaccha- rides, polymers composed of many sugar building blocks, Sugars Monosaccharides ((rom the Greek monos, single, and sacchar, sugar) generally have molecular formulas that are some ‘multiple of the unit CH,O. Glucose (C.H,,09), the most com- ‘mon monosaccharide, is of cental importance in te chemistry ‘varven's The Structure and Function of Large Biological Nolecles 69‘Aldeses (Aldehyde Sugars) Carbonyl group a end of ‘bon skeleton Ketoses (Ketone Sugars) ‘Carbonyl group within carbon skeleton “oses:3carbon sugars (GH,0,) Glyceraldehyde An inital oreacown ‘product of glucose Dihydroxyacetone An nizal breaicown product of glucose Pentoses:5-arbon sugars (C3Hy_03) Ribose Rlbulose ‘component of RNA Aan intermediate in photosythess Hexoses: 6-carbon sugars (C,H,,0,) H H Bogoon ROOF HO-C-H HOCH HoGmoH H—C—om HoGmoH HC—on 4 4 Glucose Galactose Fructose Energy sources for organisms | Aa energy sure for organisms A Figure 5.3 The structure and classification of some monosaccharides, Suoa's vay n the location of tele carbonyL ‘groups (orange, the length of ther carbon skeletons, and the spatial Brrangementarouns asymmeticcaroons (compare, for example, the purple portions of olucse and galactose) MENTE the 19705, «process was developed {har converts the glucose in cor syrup (0s Sweeter amr, Teaetse Fighrctce com syrup, a common ingredient n safe drinks and processed food, is @ miture of glucose and tructose. What type of iso- mers are glucose and iructose? See Figure 4.7, p. 62 70 unit ont The Chemisty of Lie of life. Inthe structure of glucose, we can see the tademasks of ‘a sugar: The molecule has a carbonyl group (C=O) and multiple hydroxyl groups (—OH) (Figure 5.3). Depending on the loca- tion of the carbonyl group, a sugars either an aldose (aldehyde sugar) or a ketose (ketone sugar). Glucose, for example, is an al- dose; fructose, an isomer of glucose, is a ketose. (Most names for sugars end in -ose.) Another criterion for classifying sugars is the size of the carbon skeleton, which ranges from three to seven carbons long. Glucose, fructose, and other sugars that have six carbons are called hexoses. Tioses (three-carbon sugars) and pentoses(five-carbon sugars) are also common. Sull another source of diversity for simple sugars is in the spatial arrangement of their parts around asymmetric carbons, ‘Recall that an asymmetric carbon is a carbon 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 behaviors. Although it is convenient to draw glucose with a linear carbon skeleton, this representation is not completely accu- rate. In aqueous solutions, glucose molecules, as well as most other five- and six-carbon sugars, form rings (Figure 5.4). ‘Monosaccharides, particulary glucose, are major nutrients for cells In the process known as cellular respiration, cells ex- luact energy ina series of reactions starting with glucose mol- ‘ecules. Simple-sugar molecules are not only a major fuel for cellular work, but their carbon skeletons also serve as raw ma- terial for the synthesis of other types of small organic mol- cecules, such as amino adds and fatty acids, Sugar molecules that are not immediately used in these ways are generally i corporated as monomers into disaccharides or polysaccharides. A disaccharide consists of two monosaccharides joined by a glycosidic linkage, a covalent bond formed between ‘two monosaccharides by a dehydration reaction. For exam- ple, maltose is a disaccharide formed by the linking of two molecules of glucose (Figure 5.52). Also known as malt sugat, maltose is an ingredient used in brewing beer. The most prevalent disaccharide is sucrose, which is table sugar. Its two ‘monomers are glucose and fructose (Figure 5.5b), Plants gen- erally transport carbohydrates from leaves to roots and other nonphotosynthetic organs in the form of sucrose. Lactose, ‘the sugar present in milk, is another disaccharide, inthis case a glucose molecule joined to a galactose molecule Polysaccharides Polysaccharides are macromolecules, polymers with a few hundred to a few thousand monosaccharides joined by glyco- sidic linkages, Some polysaccharides serve as storage material, Ihydrolyzed as needed to provide sugar for cells. Other poly- saccharides serve as building material for structures that{@) Linear and ring forms, chemical equilib between the linear an ing structures great favors the formation of ngs. the carbons of the sugar are numbered 1 0 6, as shown. To farm the ‘fucose rng. carton T hones to the oxygen atached to carbon 5, (b) Abbreviated ring structure. Fach SH,OH Ho oH How ‘corner represents carbon, The Tings thicker edge indicates that you ae loking atthe ing edge-on, the components attached ‘o thering le above or balow the plane of the rng A. Figure 5.4 Linear and ring forms of glucose. Stat withthe linear form of fructose (see Fgure 5.3) and draw the formation ofthe fructose ring In two steps. Fist, number the carbons staring atthe fop ofthe hear sruture Then attach carbon § via ‘oxygen to carbon 2. Compare the numberof carbons in the rctose and glucose rings {) Dehydration reaction in the synthesis of maltose. The bonding of two glucose nts forme maltose, The ‘hos nkage join he hhumber 1 unbranchee regions starch, isa branched polymer with 1-6 linkages atthe branch, points, Both of these starches are shown in Figure 5.63, "Animals store a polysaccharide called glycogen, a polymer ‘of glucose that is like amylopectin but more extensively branched (Figure 5.6b), Humans and other vertebrates store ‘lycogen mainly in liver and muscle cells. Hydrolysis of glyco- ‘gen in these cells releases glucose when the demand for sugar Increases. This stored fuel cannot sustain an animal for long, ‘however In humans, for example, glycogen stores are depleted 4n about a day unless they ate replenished by consumption of food. This is an issue of concem in low-carbohydrate diets Structural Polysaccharides Organisms build stoong materials from structural polysaccha- rides. For example, the polysaccharide called cellulose is a ‘major component of the tough walls that enclose plant cell Om a global scale, plants produce almost 10" kg (100 billion tons) of elluose per year itis the most abundant organic compound on Earth Lake starch, cellulose isa polymer of ghu- cose, but the glycosidic linkages in these two polymers difer “The diference is based on the fact that there ate actually to Slightly different ring structures for glucose (Figure 5.72). ‘When ghucose 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 (q) and beta (f), respectively. In starch, all the glucose ‘monomers are in the « configuration (Figure 5.7b), the aurangement we saw in Figures $4 and 5.5. In contrast, the 72 wiv ont The Chemisty of Lie slucose monomers of cellulose are all in the § configuration, ‘making every glucose monomer “upside down" with respect lots neighbors (Figure 5.70). ‘The differing glycosidic linkages in starch and cellulose ive the two molecules distinct three-dimensional shapes, ‘Whereas certain starch molecules ate largely helical, a celu- lose molecule is straight, Cellulose is never branched, and some hydroxyl groups on its glucose monomers are free to hydrogen-bond with the hydroxyls of other cellulose mol- ‘ecules lying parallel to it, In plant cell walls, parallel cellulose ‘molecules held together in this way are grouped into units called microfibrils (Figure 5.8), These cableslike microfibrils are a stong building material for plants and an important substance for humans because cellulose is the major con- stituent of paper and the only component of cotton, Enzymes that digest starch by hydrolyzing its a. linkages are unable to hydrolyze the f linkages of cellulose because of the distinctly diferent shapes ofthese two molecules. In fact, few organisms possess enzymes that can digest cellulose, Ani- ‘mals, 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 ofthe di- gestive tract and stimulates the lining to secrete mucus, ‘hich aids in the smooth passage of food through the tact, ‘Thus, although cellulose is not a nutrient for humans, itis an important part of a healthful diet. Most fresh fruits, vegeta- bles, and whole grains are rich in cellulose. On food pack- ages, “Insoluble fiber” refers mainly to cellulose,gander oe won vo glucose differ in the 4 uy 4 ae i ; ; gepnongrede oe i ey t ce wale pees 1 i Oe ees Bf Oeeacppecceenee 1 igure 57 Star and close structure nye EE, ge main architectural unit ofthe plant cell wal Micrefon Cellose molecules ov Parallel cellulose molecules are held together by hysrogen| bondi between hydroxyl ‘groups attached to carbon atoms and 6 A cellulose molecule fs an unbranched Ea ‘ghicose polymer. ‘cvarten s The Structure and Function of Large Biological Nolecles 75Some microorganisms can digest cellulose, breaking it down into glucose monomers. A cow harbors cellulose: digesting prokaryotes and protists in its stomach, These mi- crobes hydrolyze the cellulose of hay and grass and convert the glucose to other compounds that nourish the cow. Simi larly, a termite, which is unable to digest cellulose by itself, ‘has prokaryotes or protists living in its gut that can make ‘meal of wood. Some fungi can also digest cellulose, thereby hhelping recycle chemical elements within Earth’s ecosystems, Another important structural polysaccharide is chitin, the carbohydrate used by arthropods (insects, spiders, crus- taceans, and related animals) to build their exoskeletons (Figure 5.9). An exoskeleton is a hard case that surrounds the soft parts of an animal, Pure chitin is leathery and flexible, Dbut it becomes hardened when encrusted with calcium cat- Donate, a salt. Chitin is aso found in many fungi, which use ‘his polysaccharide rather than cellulose as the building ma- terial for their cell walls, Chitin is similar to cellulose, with, B linkages, except that the glucose monomer of chitin has a nitrogen-containing appendage (see Figure 5.9, top right) HOH Figure 5.23 A chaperonin in The computer srapnic de shows a large chaperonin protein comalex fr the bacterium & cot has anterior space shat provides a shelter forthe prope folding of nenly made polypeptides. The Eomplex consists of ‘we arotens: One proteins a hollows finder the other isa ap that can Fron titer end Jollow olincer Chaperonin iy assembled) Action: ( etn de i ‘Steps of Chaperonin OAnunfolded poe peptide enters the {jer from one en. ‘onins do not specify the final structure of a polypeptide. In- stead, they keep the new polypeptide segregated from "bad influences” in the cytoplasmic environment while it folds spontaneously. The chaperonin shown in Figure 5.23, from the bacterium E.coli a giant multiprotein complex shaped like a hollovr cylinder. The cavity provides a shelter for fold- ing polypeptides. Inthe past decade, researchers have discov- ‘ered molecular systems that interact with chaperonins and check whether proper folding has occurred. Such systems ei- ther refold the misfolded proteins correctly or mark them for destruction, Misfolding of polypeptides is a serious problem in cells, Many diseases, such as Alzheimer's, Parkinson's, and mad cow disease, are associated with an accumulation of misfolded proteins. Infact, misfolded versions of the transthyretin pro- tein featured in Figure 5.20 have been implicated in several diseases, including one form of senile dementia Even when scientists have a correctly folded protein in hand, determining its exact Unzee-dimensional structure is ‘not simple, for a single protein molecule has thousands of atoms. The first 3-D structures were worked out in 1959 for hemoglobin and a related protein. The method that made these feats possible was X-ray crystallography, which has since been used to determine the 3-D structure of many other proteins. In a recent example, Roger Komberg and his col- leagues at Stanford University used this method to elucidate the structure of RNA polymerase, an enzyme that plays a cru ial role in the expression of genes (Figure 5.24, on the next ;page). Another method for analyzing protein structure is nu- clear magnelic resonance (NMR) spectroscopy, which does not require protein crystallization. A still newer approach ‘employs bioinformatics (see Chapter 1) to predict the 3D structure of polypeptides from their amino acid sequence, X-ray exystallography, NMR spectroscopy, and bioinformatics are complementary approaches to understanding protein structure and function, NN foliea © The cap attaches, causing the linger to change shape In ha way that it creates a Ayctoohiic environment for the folding ofthe palypepride. © The cap comes off, and the properly folded protem's releases, ‘evarven s The Structure and Function of Large Biological Nolecles 85Y Figure 5.24 INQUIRY ‘What can the 3-D shape of the enzyme RNA polymerase Il tell us about its function? EXPERIMENT y 2006, Roger Komberg was awarded the Nobel rie Chemisty fr using Xray crysalograpy to determine the 3-D shape of NA pelymerase I whic binds to the DNA double helix an synthesizes NA. Alter cystalizng a complex of all vee components, Kornberg and his clleagues aimed an Xray beam through the esta. The atoms of the nyt difracted (ben) the Xrays into an ore aay that 3g tal etec- tor recorded a5 a pattern of sats called an Xray efracton pattem Ditraced xo kes youee Xa > ised Ma Cysts Digtl detector Xuay dtracton pate RESULTS Using data from X-ray diffraction patterns, aswell asthe amino id sequence determined by chemical methods, Kornberg and calleagues bhutta 3-0 model ofthe complex with the nlp o CONCLUSION fy analyzing ther model, the researchers develp a hy. pothesis about the functions of ferent regions of RNA polymerase I. For rampl, the region above tne ONA may act 3 2 lamp that holds lic acids in place (You learn more about this enzyme in Chapter 17) SOURCE A, L Gnatt etal, Structural bas of wanscrinton: an ANA poly merase elongation coralex at 3.34, Science 292 1876-1882 (2001), Ifyou were an author ofthe paper and were describing the model, what type of protein stucture would you eal the small pobpeptise spasm RNA pobmerase concert cuecx 5.4 1. Why does a denatured protein no longer function normally? 2. What parts of a polypeptide participate in the bonds that hold together secondary structure? Terary structure? 3 ‘Where would you expect a polypeptide segion that is rich in the amino acids valine, leucine, and isoleucine to be located in the folded polypep- ‘ide? Explain, For suggested answers see Appendix A. 86 owsrone The Chemistry of Life Nucleic acids store, transmit, and help express hereditary information If the primary structure of polypeptides determines a pro- tein’s shape, what determines primary structure? The amino acid sequence of a polypeptide is programmed by a discrete unit of inheritance known as a gene, Genes consist of DNA, which belongs to the class of compounds called nucleic acids, Nucleic acids are polymers made of monomers called nucleotides The Roles of Nucleic Acids Te two types of nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), enable living organisms to re- produce thelr complex components from one generation to the next, Unique among molecules, DNA provides directions ‘own replication. DNA also directs RNA synthesis and, through RNA, controls protein synthesis (Figure 5.25). DNA is the genetic material that organisms inherit from ‘their parents, Each chromosome contains one long DNA mol- ecu, usually carrying several hundred or mote genes. When 4 cell reproduces itself by dividing, its DNA molecules are ‘copied and passed along from one generation of calls to the next. Encoded in the structure of DNA is the information that or its O syne ot mann the mucus Q Movement of mRNA ino ytoplasm ‘va nuclear pore 1A Figure 5.25 DNA -> RNA — proteln. In a eukaryotic cl, DNA, in the nudlevs programs protein prosuction inthe cytoplasm by Cetating synthesis of messenger RNA (mRNA, [Te cel nucleus ‘actualy mach lager relative fo the ater elements ofthis igure)programs al the cell's activities. The DNA, however, is not dl- reclly involved in running the operations of the cell, any more than computer software by itself can print a bank state- ‘ment or read the bar code on a box of cereal. Just asa printer 4s needed to print out a statement and a scanner is needed to read a bar code, proteins are required to implement genetic programs. The molecular hardwate of the cell—the tools for biological functions—consists mostly of proteins. For exam- ple, the oxygen cartier in red blood cells s the protein hemo- globin, not the DNA that specifies its structure. How does RNA, the other type of nucleic acd, fit into gene expression, the flow of genetic information from DNA to pro- (eins? Each gene along a DNA molecule directs synthesis of a type of RNA called messenger RNA (mRNA). The mRNA mol- ecule interacts with the cel’s protein-synthesizing machinery to direct production of a polypeptide, which folds into all or part of a protein, We can summarize the flow of genetic infor- Imation as DNA ~> RNA — protein (see Figure 5.25). The sites of proteln synthesis are ny structures called ribosomes. In a eukaryotic cell, xbosomes are in the cytoplasm, but DNA re- sides in the nucleus. Messenger RNA conveys genetic instruc- tions for building proteins rom the nucleus to the cytoplasm, Prokaryotic cells lack nuclel but still use mRNA to convey a Suga-shosphate backbone (on blue background) _message from the DNA to rbosomes and other cellular eguip- ‘ment that ‘quences, In recent years, the spotlight has been tumed on other, previously unknown types of RNA that play many ‘other roles in the cell. As is so often true in biology, the story {s still being written! You'll hear more about the nevily diseov- ‘ered functions of RNA molecules in Chapter 18. ranslate the coded information into amino acid se- The Components of Nucleic Acids Nucleic acids are macromolecules that exist as polymers called polynucleotides (Fioure 5.262), As indicated by the name, ‘each polynucleotide consists of monomers called nucleotides, ‘A nucleotide in general s composed of three parts: a nitrogen containing (nitrogenous) base, a five-carbon sugar (a pentose), and one or more phosphate groups (Figure 5.26b). In a polynu- ‘eotide, each monomer has only one phosphate group. The portion of a nucleotide without any phosphate groups is called a nucleoside, ‘To build a nucleotide, le’ first consider the nitrogenous bases (Figure 5.26e). Each nitrogenous base has one or two rings that inchide nitrogen atoms. (They are called nitroge- nous bases because the nitrogen atoms tend to take up HT Nitrogenous bases Hy i ae - Nucleoside of Hoe! * oF " one ‘ytosine (©) Thyine (in DNA) rac (, in RNA) Fo, ie I i CL « grou Sugar H 4 wh send 5 cr 5 (2) Polynucleotide, oF nudeie aid 1A Figure 5.26 Components of nucleic acids. (2) pokmucleotile has 2 F as Sugarhasphate backbone with variable appendages the nivagenous bases. () A Ob’ oH ‘OH rucletide monomer includes antwogenous base, a sugar, and aphosohate group. \ithout the phosphate group, the structure i ale a hucleosice, ( A nucleoside Deoxyribose (in DNA) Ribose {in RNA) includes anirogerous base (purine or pyrimidine) and afvecarbon sugar (eoryrnose or bose (0 Nucteo fe components ‘cuarten s The Structure and Function of Large Biological Moleculesfom solution, thus acting as bases) There are two families of nitcogenous bases: pyrimidines and purines, A pyrimidine has one six-membered ring of carbon and nitrogen atoms. The members of the pyrimidine family are cytosine (C), thymine (, and uracil (U), Purines are larger, with a sixmembered ring fused to a fivemembered ring. The purines are adenine (4) and guanine (6) The specific pyrimidines and purines dit- {er in the chemical groups attached tothe ings. Adenine, gua- ‘nine, and cytosine are found in botls DNA and RNA; thymine fs found only in DNA and uracil only in RNA Now let’ add a sugar to the nitrogenous base. In DNA the sugat is deoxyribose; in RNA st is ribose (se Fgure 5.260. The only diference between these two sugars is Uhat deoxyri- bose lacks an oxygen atom on the second carbon in the ring; hhence the name deoxyribose. To distinguish the numbers ofthe sugar casbons from those used for the ing atoms of the at. ‘ached nitrogenous base, the sugar carbon numbers ofa mucleo- side or nucleotice have a prime () after them. Thus, the second carbon in the sugat ring isthe 2’ ("2 prime") carbon, and the cat- ‘bon that sticks up from the sng is called the 5" eatbon. So far, we have built a nucleoside (nitrogenous base plus sugar). To complete the construction of a nucleotide, we at- tach a phosphate group to the 5’ carbon of the sugar (ce Figure 5.260). The molecule is now a nucleoside monophos- phate, better known as a nucleotide Nucleotide Polymers Now we can see how these nucleotides are linked together to build a polynucleotide. Adjacent nucleotides are joined by a phosphodiester linkage, which consists of a phosphate group that links the sugars of two nucleotides. This bonding results in a backbone with a repeating pattern of sugarpphosphate ‘units (ee Figure 5.26a). (Note that the nitrogenous bases are ‘not part of the backbone.) The two free ends of the polymer are distinctly different from each other, One end has a phos. pphate attached to a 5’ carbon, and the other end has a hy: roxyl group on a 3° carbon; we refer to these as the $end and the 3° end, respectively. We can say that a polynucleotide hhas a builtin directionality along its sugar-phosphate back- ‘bone, from 5" to 3, somewhat like a one-way street. All along ‘this sugar-phosphate backbone are appendages consisting of the nitrogenous bases. ‘The sequence of bases along a DNA (or mRNA) polymer is ‘unique for each gene and provides very specific information {to the cell. Because genes are hundreds to thousands of nu- cleotides long, the number of posstble base sequences is effec: ‘ively limitless, A gene’s meaning to th specific sequence of the four DNA bases. For example, the se- quence S'-AGGTAACTT:3' means one thing, whereas the se- quence 5/-CGCTTTAAC' has a different meaning. Entire genes, of course, are much longer) The linear order of bases in a gene specifies the amino acid sequence—the primary cell s encoded in its 8 UwsroNe The Chemistry of Life structure—of protein, which in turn specifies that proteln’'s ‘three-dimensional structure and its function in the cell, The Structures of DNA and RNA Molecules RNA molecules usually exist as single polynucleotide chains like the one shown in Figure 5.26a, In contrast, DNA molecules have two polynucleotides, or “strands,” that spiral around an imaginary axis, forming a dowble helix (Figure 5.270). The ‘ovo sugarsphosphate backbones run in opposite 5” > 3° direc- tions fom each other; this arrangement is referred to as antiparallel, somewhat ike a divided highway. The sugar- phosphate backbones ate on the outside ofthe helix, and the nitrogenous bases are paired in the interior of the helix. The too strands are held together by hydrogen bonds between ‘the paired bases (see Figure 5.273). Most DNA molecules are very long, with thousands or even millions of basepairs. One long DNA double helix includes many genes, each one a par- ticular segment of the molecule ‘Only certain bases in the double helix are compatible with fach other. Adenine (A) always pairs with thymine (1), and ‘guanine (G) always pais with cytosine (C). I'we were to read the sequence of bases along one strand of the double helix, we ‘would know the sequence of bases along the other strand, If stretch of one strand has the base sequence 5'-AGGTCCG-3', ‘then the base-pairing rules tellus that the same stretch of the other stand must have the sequence 3TCCAGGC'S. The two strands of the double helix are complementary, each the pre- dictable counterpart of the other. Itis this feature of DNA that rakes it possible to generate two identical copies of each DNA molecule in a cell that is preparing to divide, When the cell divides, te copies are distributed to the daughter cell, making them genetically identical to the parent cell. Thus, the structure of DNA accounts for its fanetion of transmitting genetic information whenever a cell eproduces ‘Complementary base pairing can also occur between parts of two RNA molecules or even between two stretches of nue cleotides in the same RNA molecule, In fact, base pairing within an RNA molecule allows it to take on the particular ‘three-dimensional shape necessary for its function. Consides, for example, the type of RNA called transfer RNA (RNA), ‘which brings amino acids tothe ribosome during the synthe- sis ofa polypeptide. A tRNA molecule is about 80 nucleotides 4n length. Its functional shape results from base paising be- ‘ween nucleotides where complementary stretches of the ‘molecule nin antiparallel to each other (Figure 5.276). Note that in RNA, adenine (A) pairs with uracil (U); ‘thymine (1) is not present in RNA, Another difference be- tween RNA and DNA is that DNA almost always exists as a double helix, whereas RNA molecules are more variable in shape. This variability arises because the extent and location ‘of complementary base pairing within an RNA molecule dif- fers in different types of RNA, as you will see in Chapter 17.> Figure 5.27 The structures of DNA and tRNA molecules. (a) The ONA molecules usually 2 dovdle hel, wath the = Sgarahosphate backbones ofthe antparael polynucleotide strands (ymbolzes here oy Bue ritbars) onthe ousde ofthe hel Holding the ta strands together ae pars of Intragenous bases attached to each ater by hydrogen bands. Asilurtratee nee symbol shapes forthe bases, adenine (A) can irony ith thymine) and guanine (G) can pai only ith osine(C), Fach ONA stand in {hs figure the structural equvalent of the polynucleotide ciagrammed in Figure 5.28, (6)'8 tRNA molecule has a oughly shaped structure, with complementary base paring of Anparalistetenes of RNA. In RNA A pars wath yoy (2) DNA Hydrogen bonds Base arjored by nydrogen bonding Sugar-phosohate backbones Base pair joined by hydrogen bonding () Transfer RNA DNA and Proteins as Tape Measures of Evolution MEST we ae accustomed to thinking of shared traits, such as hair and milk production in mammals, as evi: dence of shared ancestors. Because we now understand that DNA carries heritable information in the form of genes, we can see that genes and their products (proteins) document the hereditary background of an organism, The linear sequences of nucleotides in DNA molecules are passed from parents to offspring; these sequences determine the amino add se. quences of proteins. Siblings have greater similarity in their DNA and proteins than do unrelated individuals of the same species, If the evolutionary view of life is valid, we should be able to extend this concept of "molecular genealogy” to rela- tionships betwreen species: We should expect two species that appear to be closely related based on fossil and anatomical ev- dence to also share a greater proportion of thelr DNA and protein sequences than do more distantly related species. In fact, that is the case, An example is the comparison of the 8 polypeptide chain of human hemoglobin with the corre. sponding hemoglobin polypeptide in other vertebrates. In this chain of 146 amino acids, humans and gorillas difer i just 1 amino acid, while humans and frogs differ in 67 amino acids. Molecular biology has added a new tape measure to the {toolkit lologists use to assess evolutionary Kinship, The Theme of Emergent Properties in the Chemistry of Life: A Review Recall that life is organized along a hierarchy of structural Ievels (see Figure 1.4). With each increasing level of order, new properties emerge. In Chapters 2-5, we have dissected the chemistry of life. But we have also begun to develop a more integrated view of life, exploring how properties emerge with increasing order, ‘We have seen that water's behavior results from the inter- actions of its molecules, each an ordered arrangement of by- {drogen and oxygen atoms, We reduced the complexity and Yaya (p. 74-77) Why ae pts nt considered tobe macromolecules or pobmen? @ Phospholipids phosphate group | Upid layer of membranes win | zinta eshte i ua nen, Yen “Revole: fou ted ings wth | + Component of cel membranes ‘tached chemical groupe (chaleners) + Sorting molecules that travel trough ‘he body (hormones) sonceen 5.4 “Socrates ‘ove nctl spe Protein include avery - + storage proteins + Sore amino aes structures resulting ina ALS + anspor proteins | Tansparsubntances wide range of functions avi + Hormones + Cootdnate orginimal responses (pp. 77-86) So: 2 J + Recepter proteins + Receive signals tom out cell Fy Proteins are the most soue- svinxeranoner | + Motor proteins + Function in el movement eer ears ae ope + Detesve proteins + Protect agninst dese ‘molecules Expl the ass for this versity concert 5.5 vege ie | BNA Stores hereditary nfrmation Prep + Sugar = deoxytose Nulele aids store, transmit 2 ae = Nitragenous ses = CG, AT ara helpvexeees peresitay | "eo + Unsly doublestranded ‘What rote does complemen- ma 7 cepesion inching ong ny bse arn pay the TNttegenovs bases = ¢,6,A,U_ | tution rom DNA te nbosomes fim + Usalysnglestranded 90 unin one The Chemistry of Life