3.1 Molecules are the building blocks of life The Chemistry of Carbon Biological macromolecules In chapter 2 we discussed how atoms combine to form ne or ganic molecule sms are small and sim- molecules. In this chapter, we will focus on organic mole ple, containing only one or a few functional groups. Oth- cules, those chemical compounds that contain carbon. The ers are large complex assemblies called macromolecules frameworks of biological molecules consist predominantly In many cases, these macromolecules are polymers, mole of carbon atoms bonded to other carbon atoms or to atoms cules built by linking together a large number of small, of oxygen, nitrogen, sulfur or hydrogen. Because carbon similar chemical subunits, like railroad cars coupled to atoms possess four valence electrons and so can form four form a train. For example, complex carbohydrates like covalent bonds, molecules containing carbon can form starch are polymers of simple ring-shaped sugars, pro- straight chains, branches, or even rings. As you can imag- teins are polymers of amino acids, and nucleic acids ine, all of these possibilities generate an mmense range of DNA and RNA) are polymers of nucleotides. Biological molecular structures and shapes macromolecules are traditionally grouped into four major Organic molecules consisting only of carbon and hydro categories: proteins, nucleic acids, lipids, and carbohy gen are called hydrocarbons. Covalent bonds between car drates(table 3.1) from fossil fuels as a primary source of energy tod, o bon and hydrogen are energy-rich. We use hydrocarbor Propane gas, for example, is a hydrocarbon consisting of a chain of three carbon atoms, with eight hydrogen atoms Ball-and- Found in: Stick Model bound to it. HHH Hydroxyl alcohols H-CC-C--H Carbonyl Because carbon-hydrogen covalent bonds store consider- able energy, hydrocarbons make good fuels. Gasoline, for example, is rich in hydrocarbons Carboxyl Amino acids O RH Functional g Carbon and hydrogen atoms both have very similar elec tronegativities. so electrons in C-C and ch bonds are Amino Ammonia evenly distributed, and there are no significant differences in charge over the molecular surface. For this reason, hy drocarbons are nonpolar. Most organic molecules that are Sulfhydryl produced by cells. however, also contain other atoms. Be- cause these other atoms often have different electronegative- ities, molecules containing them exhibit regions of positive Phospholipids, or negative charge, and so are polar. These molecules can Phosphate-0-p-oo-P-o nucleic acids. be thought of as a C-H core to which specific groups of atoms called functional groups are attached. For example, a hydrogen atom bonded to an oxygen atom(Oh) is a functional group called a bydroxy/ group Methane Functional groups have definite chemical properties that Methyl they retain no matter where they occur. The hydroxyl group, for example, is polar, because its oxygen atom, being very electronegative, draws electrons toward itself(as we FIGURE 3.2 saw in chapter 2). Figure 3.2 illustrates the hydroxyl group The primary functional chemical groups and other biologically important functional groups. Most act as units during chemical reactions and cot transfer of a functional group as an intact unit from one example, make a molecule more basic, while carboxyl groups. chemical reactions that occur within organisms involve the properties on the molecules that possess ther molecule to another make a molecule more acidic 36 Part I The Origin of Living Things
Biological Macromolecules Some organic molecules in organisms are small and simple, containing only one or a few functional groups. Others are large complex assemblies called macromolecules. In many cases, these macromolecules are polymers, molecules built by linking together a large number of small, similar chemical subunits, like railroad cars coupled to form a train. For example, complex carbohydrates like starch are polymers of simple ring-shaped sugars, proteins are polymers of amino acids, and nucleic acids (DNA and RNA) are polymers of nucleotides. Biological macromolecules are traditionally grouped into four major categories: proteins, nucleic acids, lipids, and carbohydrates (table 3.1). 36 Part I The Origin of Living Things The Chemistry of Carbon In chapter 2 we discussed how atoms combine to form molecules. In this chapter, we will focus on organic molecules, those chemical compounds that contain carbon. The frameworks of biological molecules consist predominantly of carbon atoms bonded to other carbon atoms or to atoms of oxygen, nitrogen, sulfur or hydrogen. Because carbon atoms possess four valence electrons and so can form four covalent bonds, molecules containing carbon can form straight chains, branches, or even rings. As you can imagine, all of these possibilities generate an immense range of molecular structures and shapes. Organic molecules consisting only of carbon and hydrogen are called hydrocarbons. Covalent bonds between carbon and hydrogen are energy-rich. We use hydrocarbons from fossil fuels as a primary source of energy today. Propane gas, for example, is a hydrocarbon consisting of a chain of three carbon atoms, with eight hydrogen atoms bound to it: H H H ||| H—C—C—C—H | | | H H H Because carbon-hydrogen covalent bonds store considerable energy, hydrocarbons make good fuels. Gasoline, for example, is rich in hydrocarbons. Functional Groups Carbon and hydrogen atoms both have very similar electronegativities, so electrons in C—C and C—H bonds are evenly distributed, and there are no significant differences in charge over the molecular surface. For this reason, hydrocarbons are nonpolar. Most organic molecules that are produced by cells, however, also contain other atoms. Because these other atoms often have different electronegativities, molecules containing them exhibit regions of positive or negative charge, and so are polar. These molecules can be thought of as a C—H core to which specific groups of atoms called functional groups are attached. For example, a hydrogen atom bonded to an oxygen atom (—OH) is a functional group called a hydroxyl group. Functional groups have definite chemical properties that they retain no matter where they occur. The hydroxyl group, for example, is polar, because its oxygen atom, being very electronegative, draws electrons toward itself (as we saw in chapter 2). Figure 3.2 illustrates the hydroxyl group and other biologically important functional groups. Most chemical reactions that occur within organisms involve the transfer of a functional group as an intact unit from one molecule to another. 3.1 Molecules are the building blocks of life. Hydroxyl Carbonyl Carboxyl Amino Sulfhydryl Phosphate Methyl Carbohydrates, alcohols Amino acids, vinegar Group Structural Formula Ball-andStick Model Found In: Formaldehyde Ammonia Proteins, rubber Phospholipids, nucleic acids, ATP Methane gas S H O– P O– O O C H H H OH O OH C H H N C O H H O O– O P H N S O H O– H H C H H O C O O C FIGURE 3.2 The primary functional chemical groups. These groups tend to act as units during chemical reactions and confer specific chemical properties on the molecules that possess them. Amino groups, for example, make a molecule more basic, while carboxyl groups make a molecule more acidic
Table 3.1 Macromolecules Macromolecule Function E PROTEINS Globula Amino acids Modified glucose Hemoglobin Structural Catalysis; transport Hair: silk NUCLEIC ACIDS upport Nucleotides Encodes genes oshIn RNA cotide Needed for gene expression Messenger rNa LIPIDS Glycerol and three fatty acids Energy storage Butter; corn oil; soap Phospholipids Glycerol, two fatty acid Cell membranes phosphate, and polar R groups Prostaglandins Five-carbon rings with two Chemical messengers Prostaglandin E (PGE) Four fused carbon rings Membranes: hormones Cholesterol; estrogen Ie Long carbon chains Pi gments; structural Carotene: rubber CARBOHYDRATES Starch, glycogen Glucose Energy storage Cell walls Paper; strings of celery Chitin Structural support Crab shells Building macromolecules FIGURE 3.3 Making and breakin 2o Although the four categories of macromolecules contain macromolecules ferent kinds of subunits, they are all assembled in the same (a) Biological fundamental way: to form a covalent bond between two sub- macromolecules are unit molecules, an -OH group is removed from one sub- lymers formed by unit and a hydrogen atom(H) is removed from the other linking subunits (figure 3. 3a). This condensation reaction is called a dehy together. The HO= covalent bond dration synthesis, because the removal of the -OH group between the subunits and h during the synthesis of a new molecule in effect con- hydration synthesis stitutes the removal of a molecule of water(H2O). For every esIs subunit that is added to a macromolecule. one water mole cule is removed. Energy is required to break the chemical process that creates bonds when water is extracted from the subunits, so cells water molecule for must supply energy to assemble macromolecules. These and every bond formed. (b) other biochemical reactions require that the reacting sub- reaking the bond stances be held close together and that the correct chemical between subunits bonds be stressed and broken. This process of positioning stressing, termed catalysis, is carried out in cells by of a water molecule special class of teins with a subsequent Hydrolysis Cells disassemble macromolecules into their constituent release of energy,a subunits by performing reactions that are essentially the re- hydrolysis of removed(figure 3.36). In this process, which is called hydrolysis( Greek hydro,“ water”+lse," break”), a hydro- Polymers are large molecules consisting of long chains gen atom is attached to one subunit and a hydroxyl group of similar subunits joined by dehydration reactions. In a to the other, breaking a specific covalent bond in the dehydration reaction, a hydroxyl (OH) group is macromolecule Hydrolytic reactions release the energy removed from one subunit and a hydrogen atom(H)is that was stored in the bonds that were broken removed from the other Chapter 3 The Chemical Building Blocks of Life 37
Building Macromolecules Although the four categories of macromolecules contain different kinds of subunits, they are all assembled in the same fundamental way: to form a covalent bond between two subunit molecules, an —OH group is removed from one subunit and a hydrogen atom (H) is removed from the other (figure 3.3a). This condensation reaction is called a dehydration synthesis, because the removal of the —OH group and H during the synthesis of a new molecule in effect constitutes the removal of a molecule of water (H2O). For every subunit that is added to a macromolecule, one water molecule is removed. Energy is required to break the chemical bonds when water is extracted from the subunits, so cells must supply energy to assemble macromolecules. These and other biochemical reactions require that the reacting substances be held close together and that the correct chemical bonds be stressed and broken. This process of positioning and stressing, termed catalysis, is carried out in cells by a special class of proteins known as enzymes. Cells disassemble macromolecules into their constituent subunits by performing reactions that are essentially the reverse of dehydration—a molecule of water is added instead of removed (figure 3.3b). In this process, which is called hydrolysis (Greek hydro, “water” + lyse, “break”), a hydrogen atom is attached to one subunit and a hydroxyl group to the other, breaking a specific covalent bond in the macromolecule. Hydrolytic reactions release the energy that was stored in the bonds that were broken. Polymers are large molecules consisting of long chains of similar subunits joined by dehydration reactions. In a dehydration reaction, a hydroxyl (—OH) group is removed from one subunit and a hydrogen atom (H) is removed from the other. Chapter 3 The Chemical Building Blocks of Life 37 Table 3.1 Macromolecules Macromolecule Subunit Function Example PROTEINS Globular Structural NUCLEIC ACIDS DNA RNA LIPIDS Fats Phospholipids Prostaglandins Steroids Terpenes CARBOHYDRATES Starch, glycogen Cellulose Chitin Hemoglobin Hair; silk Chromosomes Messenger RNA Butter; corn oil; soap Lecithin Prostaglandin E (PGE) Cholesterol; estrogen Carotene; rubber Potatoes Paper; strings of celery Crab shells Amino acids Amino acids Nucleotides Nucleotides Glycerol and three fatty acids Glycerol, two fatty acids, phosphate, and polar R groups Five-carbon rings with two nonpolar tails Four fused carbon rings Long carbon chains Glucose Glucose Modified glucose Catalysis; transport Support Encodes genes Needed for gene expression Energy storage Cell membranes Chemical messengers Membranes; hormones Pigments; structural Energy storage Cell walls Structural support H2O H2O HO HO H HO H H H HO Energy Dehydration synthesis HO H H HO Energy Hydrolysis (a) (b) FIGURE 3.3 Making and breaking macromolecules. (a) Biological macromolecules are polymers formed by linking subunits together. The covalent bond between the subunits is formed by dehydration synthesis, an energy-requiring process that creates a water molecule for every bond formed. (b) Breaking the bond between subunits requires the returning of a water molecule with a subsequent release of energy, a process called hydrolysis
2 Proteins perform the chemistry of the cell The Many Functions of Proteins cals they work on, facilitating chemical reactions by stressing particular chemical bonds. We will begin our discussion of macromolecules that make up the bodies of organisms with proteins(see table 3. 1). The 2. Defense. Other globular proteins use their shapes proteins within living organisms are immensely diverse in These cell surface receptors form the core of the structure and function(table 3.2 and figure 3. 4) ody's hormone and immune systems 1. Enzyme catalysis. We have already encountered A variety of globular proteins transpor one class of proteins, enzymes, which are biological specific small molecules and ions. The transport pro catalysts that facilitate specific chemical reactions. Be- tein hemoglobin, for example, transports oxygen in cause of this property, the appearance of enzymes was the blood, and myoglobin, a similar protein, transport one of the most important events in the evolution of oxygen in muscle. Iron is transported in blood by the life. Enzymes are globular proteins, with a three- protein transferrin dimensional shape that fits snugly around the chemi- Table 3.2 The Many Functions of Proteins Function Class of protein Examples Use Metabolism(Catalysis) Enzymes Hydrolytic enzymes Cleave polysaccharides Proteases Break down proteins Polymerase Produce nucleic acids Kinases Phosphorylate sugars and Defense Immunoglobulins Antibodies lark foreign proteins for Cell recognition Toxins Snake venom Block nerve function Transport throughout body Cell surface antigens MHC proteins “Sef" recognition Carries O, and CO, in blood Myoglobin Carries O, and CO, in muscle Cytochromes Electron transport Membrane transport Transporters assiut pu Excitable membranes Proton pump Chemiosmosis 山 nion channels Transport Cl-ions Structure/Support Collagen Cartilage Keratin Fibrin Blood clot Motion Muscle Actin Contraction of muscle fibers Myosin Contraction of muscle fibers Osmotic regulation Albumin Serum albumin Maintains osmotic concentration f blood Regulation of gene action Repressors lac repressor Regulates transcription Regulation of body functions Hormones Insulin Controls blood glucose levels Vasopressin Increases water retention by Regulates uterine contractions and milk production Ion binding Ferritin Stores iron, especially in spleen Casein Stores ions in milk Calmodulin Binds calcium ions 38 Part i The Origin of Living things
The Many Functions of Proteins We will begin our discussion of macromolecules that make up the bodies of organisms with proteins (see table 3.1). The proteins within living organisms are immensely diverse in structure and function (table 3.2 and figure 3.4). 1. Enzyme catalysis. We have already encountered one class of proteins, enzymes, which are biological catalysts that facilitate specific chemical reactions. Because of this property, the appearance of enzymes was one of the most important events in the evolution of life. Enzymes are globular proteins, with a threedimensional shape that fits snugly around the chemicals they work on, facilitating chemical reactions by stressing particular chemical bonds. 2. Defense. Other globular proteins use their shapes to “recognize” foreign microbes and cancer cells. These cell surface receptors form the core of the body’s hormone and immune systems. 3. Transport. A variety of globular proteins transport specific small molecules and ions. The transport protein hemoglobin, for example, transports oxygen in the blood, and myoglobin, a similar protein, transports oxygen in muscle. Iron is transported in blood by the protein transferrin. 38 Part I The Origin of Living Things 3.2 Proteins perform the chemistry of the cell. Table 3.2 The Many Functions of Proteins Function Class of Protein Examples Use Metabolism (Catalysis) Defense Cell recognition Transport throughout body Membrane transport Structure/Support Motion Osmotic regulation Regulation of gene action Regulation of body functions Storage Enzymes Immunoglobulins Toxins Cell surface antigens Globins Transporters Fibers Muscle Albumin Repressors Hormones Ion binding Hydrolytic enzymes Proteases Polymerases Kinases Antibodies Snake venom MHC proteins Hemoglobin Myoglobin Cytochromes Sodium-potassium pump Proton pump Anion channels Collagen Keratin Fibrin Actin Myosin Serum albumin lac repressor Insulin Vasopressin Oxytocin Ferritin Casein Calmodulin Cleave polysaccharides Break down proteins Produce nucleic acids Phosphorylate sugars and proteins Mark foreign proteins for elimination Block nerve function “Self” recognition Carries O2 and CO2 in blood Carries O2 and CO2 in muscle Electron transport Excitable membranes Chemiosmosis Transport Cl– ions Cartilage Hair, nails Blood clot Contraction of muscle fibers Contraction of muscle fibers Maintains osmotic concentration of blood Regulates transcription Controls blood glucose levels Increases water retention by kidneys Regulates uterine contractions and milk production Stores iron, especially in spleen Stores ions in milk Binds calcium ions
(c) FIGURE 3. 4 Some of the more common structural proteins. (a) Collagen: strings of a tennis racket from gut tissue;(b)fibrin: scanning electron micrograph of a blood clot(3000x); (o)keratin: a peacock feather; (d) silk: a spider's web; (e) keratin: human hair 4. Support. Fibrous, or threadlike, proteins play struc- 6. Regulation. Small proteins called hormones serve tural roles; these structural proteins(see figure 3. 4)in- as intercellular messengers in animals. Proteins also clude keratin in hair fibrin in blood clots and col play many regulatory roles within the cell, turning on lagen, which forms the matrix of skin, ligaments and shutting off genes during development, for exam- tendons, and bones and is the most abundant protein ole. In addition, proteins also receive information, act ing as cell surface receptors 5. Motion. Muscles contract through the sliding mo- tion of two kinds of protein filament: actin and myo- sin. Contractile proteins also play key roles in the Proteins carry out array of functions, including cell,s cytoskeleton and in moving materials within of substances, motion and regulation of cell ells Chapter 3 The Chemical Building Blocks of Life 39
4. Support. Fibrous, or threadlike, proteins play structural roles; these structural proteins (see figure 3.4) include keratin in hair, fibrin in blood clots, and collagen, which forms the matrix of skin, ligaments, tendons, and bones and is the most abundant protein in a vertebrate body. 5. Motion. Muscles contract through the sliding motion of two kinds of protein filament: actin and myosin. Contractile proteins also play key roles in the cell’s cytoskeleton and in moving materials within cells. 6. Regulation. Small proteins called hormones serve as intercellular messengers in animals. Proteins also play many regulatory roles within the cell, turning on and shutting off genes during development, for example. In addition, proteins also receive information, acting as cell surface receptors. Proteins carry out a diverse array of functions, including catalysis, defense, transport of substances, motion, and regulation of cell and body functions. Chapter 3 The Chemical Building Blocks of Life 39 (a) (b) (c) (d) (e) FIGURE 3.4 Some of the more common structural proteins. (a) Collagen: strings of a tennis racket from gut tissue; (b) fibrin: scanning electron micrograph of a blood clot (3000×); (c) keratin: a peacock feather; (d) silk: a spider’s web; (e) keratin: human hair
Amino Acids Are the Building Blocks Amino acid Amino acid of proteins H③ H⑧ Although proteins are complex and versatile molecules, they H一N一C-C-⑥H N一C-C-OH all of only 20 amino acic Many scientists believe amino acids were among the first molecules formed in the early earth. It seems highly likely nat the oceans that existed early in the history of the earth contained a wide variety of amino acids H2o Amino acid structure An amino acid is a molecule containing an amino group (NH2), a carboxyl group(COOH), and a hydrogen atom. all bonded to a central carbon atom R H③H③ HN-C-COOH H-N-C-C-N-C-C-OH H O H O Each amino acid has unique chemical properties deter mined by the nature of the side group (indicated by R)cova- The peptide bond. A peptide bond forms when the -NH2 end lently bonded to the central carbon atom. For example of one amino acid joins to the-COOH end of another. Because when the side group is--CHzOH, the amino acid (serine) is of the partial double-bond nature of peptide bonds, the resulting polar, but when the side group is--CH3, the amino acid peptide chain cannot rotate freely around these bonds lanine)is nonpolar. The 20 common amino acids are ouped into five chemical classes, based on their side 1. Nonpolar amino acids, such as leucine, often have r forming a covalent bond. a covalent bond that links two groups that contain--CH2 or--CH3 amino acids is called a peptide bond (figure 3.5). The two 2. Polar uncharged amino acids, such as threonine, have amino acids linked by such a bond are not free to rotate R groups that contain oxygen(or only-H) around the N-C linkage because the peptide bond has a 3. ionizable amino acids, such as glutamic acid, have partial double-bond character, unlike the N-C and C-C groups that contain acids or bases. bonds to the central carbon of the amino acid, the stiffness 4. Aromatic amino acids, such as phenylalanine, have r of the peptide bond is one factor that makes it possible for groups that contain an organic(carbon) ring with al chains of amino acids to form coils and other regula ternating single and double bonds of one or more lon properties; methionine often is the first amino acid in polypeptides, composed of amino acids linked by peptide a chain of amino acids, proline causes kinks in chains, bonds. It was not until the pioneering work of Frederick and cysteine links chains together Sanger in the early 1950s that it became clear that each kind of protein had a specific amino acid sequence. Sanger Each amino acid affects the shape of a protein differently succeeded in determining the amino acid sequence of insu- depending on the chemical nature of its side group Portions lin and in so doing demonstrated clearly that this prot of a protein chain with numerous nonpolar amino acids, for had a defined sequence the same for all insulin molecules example, tend to fold into the interior of the protein by hy- in the solution. Although many different amino acids occur drophobic exclusio n nature, only 20 commonly occur in proteins. Figure 3.6 illustrates these 20"common"amino acids and their side Proteins are polymers of Amino acids groups In addition to its r group, each amino acid, when ionized, a protein is a polymer containing a combination of up has a positive amino(NHs group at one end and a ne o to 20 different kinds of amino acids. The amino acids tive carboxyl(Coo) group at the other end. The amir fall into five chemical classes, each with different and carboxyl groups on a pair of amino acids can undergo a properties. These properties determine the nature of condensation reaction, losing a molecule of water and the resu 40 Part I The Origin of Living things
Amino Acids Are the Building Blocks of Proteins Although proteins are complex and versatile molecules, they are all polymers of only 20 amino acids, in a specific order. Many scientists believe amino acids were among the first molecules formed in the early earth. It seems highly likely that the oceans that existed early in the history of the earth contained a wide variety of amino acids. Amino Acid Structure An amino acid is a molecule containing an amino group (—NH2), a carboxyl group (—COOH), and a hydrogen atom, all bonded to a central carbon atom: R | H2N—C—COOH | H Each amino acid has unique chemical properties determined by the nature of the side group (indicated by R) covalently bonded to the central carbon atom. For example, when the side group is —CH2OH, the amino acid (serine) is polar, but when the side group is —CH3, the amino acid (alanine) is nonpolar. The 20 common amino acids are grouped into five chemical classes, based on their side groups: 1. Nonpolar amino acids, such as leucine, often have R groups that contain —CH2 or —CH3. 2. Polar uncharged amino acids, such as threonine, have R groups that contain oxygen (or only —H). 3. Ionizable amino acids, such as glutamic acid, have R groups that contain acids or bases. 4. Aromatic amino acids, such as phenylalanine, have R groups that contain an organic (carbon) ring with alternating single and double bonds. 5. Special-function amino acids have unique individual properties; methionine often is the first amino acid in a chain of amino acids, proline causes kinks in chains, and cysteine links chains together. Each amino acid affects the shape of a protein differently depending on the chemical nature of its side group. Portions of a protein chain with numerous nonpolar amino acids, for example, tend to fold into the interior of the protein by hydrophobic exclusion. Proteins Are Polymers of Amino Acids In addition to its R group, each amino acid, when ionized, has a positive amino (NH3 +) group at one end and a negative carboxyl (COO–) group at the other end. The amino and carboxyl groups on a pair of amino acids can undergo a condensation reaction, losing a molecule of water and forming a covalent bond. A covalent bond that links two amino acids is called a peptide bond (figure 3.5). The two amino acids linked by such a bond are not free to rotate around the N—C linkage because the peptide bond has a partial double-bond character, unlike the N—C and C—C bonds to the central carbon of the amino acid. The stiffness of the peptide bond is one factor that makes it possible for chains of amino acids to form coils and other regular shapes. A protein is composed of one or more long chains, or polypeptides, composed of amino acids linked by peptide bonds. It was not until the pioneering work of Frederick Sanger in the early 1950s that it became clear that each kind of protein had a specific amino acid sequence. Sanger succeeded in determining the amino acid sequence of insulin and in so doing demonstrated clearly that this protein had a defined sequence, the same for all insulin molecules in the solution. Although many different amino acids occur in nature, only 20 commonly occur in proteins. Figure 3.6 illustrates these 20 “common” amino acids and their side groups. A protein is a polymer containing a combination of up to 20 different kinds of amino acids. The amino acids fall into five chemical classes, each with different properties. These properties determine the nature of the resulting protein. 40 Part I The Origin of Living Things H — H — N — C — OH O — C — H — H H2O — H — N — C — OH O — C — H — Amino acid Amino acid H — H — N — C — O —— —— — C — H — H — N — C — OH O —— —— — C — H — Polypeptide chain R R R R FIGURE 3.5 The peptide bond. A peptide bond forms when the —NH2 end of one amino acid joins to the —COOH end of another. Because of the partial double-bond nature of peptide bonds, the resulting peptide chain cannot rotate freely around these bonds