Alberts Molecular Biology of the Cell 7th Chapter 2 PDF

49 CHAPTER Cell Chemistry and Bioenergetics...

49 CHAPTER Cell Chemistry and Bioenergetics 2 It is at first sight difficult to accept the idea that living creatures are merely chemical systems. Their incredible diversity of form, their seemingly purposeful IN THIS CHAPTER behavior, and their ability to grow and reproduce all seem to set them apart from the world of solids, liquids, and gases that chemistry normally describes. Indeed, The Chemical Components of until the late nineteenth century, animals were generally believed to contain a Vital Force—an “animus”—that was responsible for their distinctive properties. a Cell We now know that there is nothing in living organisms that disobeys chem- Catalysis and the Use of Energy ical or physical laws. However, the chemistry of life is indeed special. First, life depends on chemical reactions that take place in aqueous solution, and it is based by Cells overwhelmingly on carbon compounds, the study of which is known as organic chemistry. Second, although cells contain a variety of small carbon-containing How Cells Obtain Energy molecules, most of the carbon atoms present are incorporated into enormous poly- from Food meric molecules—chains of chemical subunits linked end-to-end. It is the unique properties of these macromolecules that enable cells and organisms to grow and reproduce—and to do all the other things that are characteristic of life. Third, and most important, cell chemistry is enormously complex: even the simplest cell is vastly more complicated in its chemistry than any other chemical system known. In fact, we now recognize that the many interlinked networks of chemical reactions in cells can give rise to so-called emergent properties, which will require the devel- opment of new experimental and computational methods to understand. Much of the information in this chapter is summarized—and in some cases further elaborated—in the nine two-page Panels with which the chapter ends (Panels 2–1 to 2–9). Although the Panels will be cited at appropriate places in the text, they should also be useful for refreshing background knowledge when read- ing later chapters. THE CHEMICAL COMPONENTS OF A CELL Figure 2–1 The main elements in cells, highlighted in the periodic table. When Living organisms are made of only a small selection of the 92 naturally occurring ordered by their atomic number and elements, four of which—carbon (C), hydrogen (H), nitrogen (N), and oxygen (O)— arranged in this manner, elements fall make up 96.5% of an organism’s weight (Figure 2–1). The atoms of these into vertical columns that show similar properties. atomic number The four elements highlighted in red constitute 99% of the total number of 1 atoms present in the human body (and H atomic weight He 1 96.5% of its weight). An additional seven 5 6 7 8 9 elements, highlighted in blue, together Li Be B C N O F Ne represent about 0.9% of the total atoms in 11 12 14 16 19 11 12 14 15 16 17 our bodies. The elements shown in green Na Mg Al Si P S Cl Ar are required in trace amounts by humans. 23 24 28 31 32 35 It remains unclear whether those elements 19 20 23 24 25 26 27 28 29 30 34 K Ca Sc V Cr Mn Fe Co Ni Cu Zn Ga Ge As Se Br Kr shown in yellow are essential in humans. Ti 39 40 51 52 55 56 59 59 64 65 79 The chemistry of life is therefore 42 53 predominantly the chemistry of lighter Rb Sr Y Zr Nb Mo Tc Ru Rh Pd Ag Cd In Sn Sb Te I Xe elements. The atomic weights shown here 96 127 are those of the most common isotope of Cs Ba La Hf Ta W Re Os Ir Pt Au Hg Tl Pb Bi Po At Rn each element. The vertical red line marks a break in the periodic table where a group of Fr Ra Ac Rf Db large atoms with similar chemical properties is omitted. MBOC7_ptr_ch02_049-114.indd 49 08/12/21 11:24 AM  50 Chapter 2: Cell Chemistry and Bioenergetics ATP average hydrolysis C–C bond thermal motions in cell breakage ENERGY CONTENT (kJ/mole) 1 10 100 1000 10,000 kJ noncovalent bond green complete breakage in water light glucose oxidation Figure 2–2 Some energies important for cells. A crucial property of any bond—covalent or noncovalent—is its strength. Bond strength is measured by the amount of energy that must be supplied to break it, expressed in units of either kilojoules per mole (kJ/mole) or kilocalories per mole (kcal/mole). Thus if 100 kJ of energy must be supplied to break 6 × 1023 bonds of a specific type (that is, 1 mole of these bonds), then the strength of that bond is 100 kJ/mole. Note that, in this diagram, energies are compared on a logarithmic scale. (Typical strengths and lengths of the main classes of chemical bonds are given in Table 2–1, later in text.) One joule (J) is the amount of energy required to move an object a distance of 1 meter (m) against a force of 1 newton (N). This MBoC7 m2.02/2.02 measure of energy is derived from the SI units (Système International d’Unités) universally employed by physical scientists. A second unit of energy, often used by cell biologists, is the kilocalorie (kcal):1 calorie (cal) is the amount of energy needed to raise the temperature of 1 gram (g) of water by 1°C. One kilojoule (kJ) is equal to 0.239 kcal. elements are linked together by covalent bonds to form molecules (see Panel 2–1, pp. 94–95). Because covalent bonds are typically 100 times stronger than the thermal energies within a cell, they resist being pulled apart by thermal motions, (A) and they are normally broken only during biologically catalyzed chemical δ+ δ+ reactions that are of use to the cell. Noncovalent bonds are much weaker H H (Figure 2–2), but sets of them allow molecules to recognize each other and _ reversibly associate, which is critical for the vast majority of biological functions. δ+ δ _ δ O H O Water Is Held Together by Hydrogen Bonds polar hydrogen H Because 70% of the weight of a cell is water, the reactions that make life pos- covalent bond δ+ sible occur in an aqueous environment. Life on Earth is thought to have begun bond in shallow bodies of water that had concentrated essential molecules, and the conditions in that primeval environment have left a permanent stamp on (B) the chemistry of all living things. O H O The chemical properties of water are reviewed in Panel 2–2 (pp. 96–97). In a water molecule (H2O), the two H atoms are linked to the O atom by covalent O H N bonds that are highly polar, inasmuch as the O atom attracts electrons more N H O strongly than does the H atom. Consequently, there is a preponderance of pos- itive charge on the two H atoms and of negative charge on the O atom. When N H N a positively charged region of one water molecule (that is, one of its H atoms) donor acceptor approaches a negatively charged region (that is, the O atom) of a second water atom atom molecule, the electrical attraction between them can result in a hydrogen bond Figure 2–3 The noncovalent hydrogen (Figure 2–3A). These bonds are much weaker than covalent bonds and are easily bond. (A) A hydrogen bond forms between broken by the random thermal motions that reflect the heat energy of the mol- two water molecules. The slight positive ecules. Thus, each bond lasts only a very short time. But the combined effect charge associated with the hydrogen atom is electrically attracted to the slight negative of many weak bonds can be profound. For example, each water molecule can charge of the oxygen atom. This causes form hydrogen bonds through its two H atoms to two other water molecules, water to exist as a large hydrogen-bonded producing a network in which hydrogen bonds are being continually broken and network (see MBoC7Panel 2–2, pp. 96–97). e2.14/2.03 formed. It is only because of these hydrogen bonds that link water molecules (B) In cells, hydrogen bonds commonly together that water is a liquid at room temperature—with a high boiling point form between molecules that contain an oxygen or nitrogen. The atom bearing and high surface tension—rather than a gas. the hydrogen is considered the H-bond Hydrogen bonds are not limited to water, and they are central to much of donor, and the atom that interacts with biology. This bond represents a special form of polar interaction in which an elec- the hydrogen is the H-bond acceptor. This tropositive hydrogen atom is shared by two electronegative atoms. The hydrogen type of dipole–dipole interaction is of critical in this bond can be viewed as a proton that has partially dissociated from a donor importance in biology. For this reason, and because it is highly directional, the atom, allowing it to be shared by a second, acceptor atom. Unlike a typical electro- hydrogen bond receives special attention static interaction, this bond is highly directional—being strongest when a straight among the set of noncovalent attractions line can be drawn between all three of the involved atoms (Figure 2–3B). that we discuss next. MBOC7_ptr_ch02_049-114.indd 50 08/12/21 11:24 AM  THE CHEMICAL COMPONENTS OF A CELL 51 Molecules, such as alcohols, that contain polar bonds and that can form hydrogen bonds with water dissolve readily in water. Molecules carrying charges (ions) likewise interact favorably with water. Such molecules are termed hydro- philic, meaning that they are water-loving. Many of the molecules in the aqueous environment of a cell necessarily fall into this category, including sugars, DNA, RNA, and most proteins. Hydrophobic (water-fearing) molecules, by contrast, are uncharged and form few or no hydrogen bonds, and so do not dissolve in water. Hydrocarbons are an important example. In these molecules, all of the H atoms are covalently linked to C atoms by a largely nonpolar bond; thus, they cannot form effective hydrogen bonds to other molecules (see Panel 2–1, pp. 94–95). This makes the hydrocarbon as a whole hydrophobic—a property that is exploited in cells, whose membranes are constructed from molecules that have long hydrocarbon tails, as we shall see in Chapter 10. Four Types of Noncovalent Attractions Help Bring Molecules Together in Cells Much of biology depends on the specific binding between different molecules caused by three types of noncovalent bonds—hydrogen bonds, electrostatic attractions (ionic bonds), and van der Waals attractions—combined with a fourth factor that can push molecules together: the hydrophobic force. Electrostatic attractions are strongest when the atoms involved are fully charged, or ionized. But a weaker electrostatic attraction occurs between mole­ cules that contain polar covalent bonds. Like hydrogen bonds, electrostatic attractions are extremely important in biology. For example, any large mole- cule with many polar groups will have a pattern of partial positive and negative charges on its surface. When such a molecule encounters a second molecule with a complementary set of charges, the two will be drawn to each other by electro- static attraction. In addition to hydrogen bonds and electrostatic attractions, a third type of noncovalent bond, called a van der Waals attraction, comes into play when any two atoms approach each other closely. These weak, nonspecific interactions are due to fluctuations in the distribution of electrons in every atom, which can generate a transient attraction when the atoms are in very close proximity. These attractions occur in all types of molecules, even those that are nonpolar. The relative lengths and strengths of these three types of noncovalent bonds are compared to the length and strength of covalent bonds in Table 2–1, both in the presence and in the absence of water. Note that, because water forms com- peting interactions with the involved molecules, the strength of both electrostatic attractions and hydrogen bonds is greatly weakened inside of the cell. The fourth effect that often brings molecules together in water is not, strictly speaking, a bond at all. However, a very important hydrophobic force is caused by a pushing of nonpolar surfaces out of the hydrogen-bonded water network, where they would otherwise physically interfere with the highly favorable TABLE 2–1 Covalent and Noncovalent Chemical Bonds Strength (kJ/mole**) Bond type Length (nm) In vacuum In water Covalent 0.10 377 (90) 377 (90) Noncovalent Ionic* 0.25 335 (80) 12.6 (3) Hydrogen 0.17 16.7 (4) 4.2 (1) van der Waals 0.35 0.4 (0.1) 0.4 (0.1) attraction (per atom) *An ionic bond is an electrostatic attraction between two fully charged atoms. **Values in parentheses are kcal/mole. 1 kJ = 0.239 kcal and 1 kcal = 4.18 kJ. MBOC7_ptr_ch02_049-114.indd 51 08/12/21 11:24 AM  52 Chapter 2: Cell Chemistry and Bioenergetics interactions between water molecules. Bringing any two nonpolar surfaces together reduces their contact with water, and in this sense, the force is nonspe- cific. Nevertheless, we shall see in Chapter 3 that hydrophobic forces are central to the proper folding of protein molecules. The properties of the four types of noncovalent attractions are presented in Panel 2–3 (pp. 98–99). Although each individual noncovalent attraction would be much too weak to be effective in the face of thermal motions, the energies of these noncovalent attractions can sum to create a strong force between two separate molecules. Thus, it is an entire set of noncovalent attractions that enables the complementary surfaces of two macromolecules to hold the two macromolecules together (Figure 2–4). Some Polar Molecules Form Acids and Bases in Water One of the simplest kinds of chemical reaction, and one that has a considerable signifi­cance for cells, takes place when a molecule containing a highly polar cova- lent bond between a hydrogen and another atom dissolves in water. The hydrogen atom in such a molecule has given up its electron almost entirely to the compan- ion atom, and so exists as an almost naked positively charged hydrogen nucleus; in other words, a proton (H1). When this polar molecule becomes surrounded by water molecules, the proton will be attracted to the partial negative charge on the O atom of an adjacent water molecule. The proton can easily dissociate from its original partner and associate instead with the oxygen atom of the water molecule, generating a hydronium ion (H3O1) (Figure 2–5A). The reverse reac- tion also takes place very readily, so in an aqueous solution protons are constantly flitting to and fro between one molecule and another. Substances that release protons when they dissolve in water, thus forming Figure 2-4 Schematic indicating how two macromolecules with H3O+, are termed acids. The higher the concentration of H3O+, the more acidic complementary surfaces can bind tightly the solution. H3O+ is present even in pure water, at a concentration of 10–7 M, to one another through noncovalent as a result of the movement of protons from one water molecule to another interactions. Noncovalent chemical bonds (Figure 2–5B). By convention, the H3O+ concentration is usually referred to as have less than 1/20 the strength of a the H+ concentration, even though most protons in an aqueous solution are covalent bond. They are able to produce tight binding only when many of them present as H3O+. As explained in Panel 2–2, to avoid the use of unwieldy num- are formed simultaneously. Although only bers the concentration of H3O+ is expressed using a logarithmic scale called the electrostatic attractions are illustrated here, pH scale. Pure water has a pH of 7.0 and is said to be neutral; that is, neither acidic in reality all four noncovalent forces often MBoC7 contribute m2.03/2.04 to holding two macromolecules (pH < 7) nor basic (pH > 7). together (Movie 2.1). Acids are characterized as being strong or weak, depending on how readily they give up their protons to water. Strong acids, such as hydrochloric acid (HCl), easily lose their protons. Acetic acid, on the other hand, is a weak acid because it holds on to its proton more tightly when dissolved in water. Many of the acids important in the cell—such as molecules containing a carboxyl (COOH) group—are weak acids. Because the proton of a hydronium ion can be passed readily to many types of molecules in cells, altering their character, the concentration of H3O+ inside a cell (the acidity) must be closely regulated. Acids—especially weak acids—will give O H O H CH3 C + O CH3 C + H O + O H H O H δ– δ+ acetic acid water acetate hydronium ion ion (A) Figure 2–5 How protons readily move in aqueous solutions. (A) The reaction H H that takes place when a molecule of acetic O H O O H + O acid dissolves in water. At pH 7, nearly all H H proton moves H + H of the acetic acid is present as acetate ion. from one + – (B) Water molecules continually exchange H2O H2O molecule to H3O OH protons with each other to form hydronium the other and hydroxyl ions. These ions in turn hydronium hydroxyl (B) ion ion rapidly recombine to form water molecules. MBOC7_ptr_ch02_049-114.indd 52 08/12/21 11:24 AM  THE CHEMICAL COMPONENTS OF A CELL 53 up their protons more readily if the concentration of H3O+ in solution is low and will tend to receive them back if the concentration in solution is high. The opposite of an acid is a base. Any molecule capable of accepting a pro- ton from a water molecule is called a base. Sodium hydroxide (NaOH) is basic (the term alkaline is also used) because it dissociates readily in aqueous solu- tion to form Na+ ions and OH– ions. Because of this property, NaOH is called a strong base. More important in living cells, however, are the weak bases— those that have a weak tendency to reversibly accept a proton from water. Many biologically important molecules contain an amino (NH2) group. This group is a weak base that can generate OH– by taking a proton from water: –NH2 + H2O → –NH3+ + OH– (see Panel 2–2, pp. 96–97). Because an OH– ion combines with an H3O+ ion to form two water molecules, any increase in the OH– concentration forces a decrease in the concentration of H3O+, and vice versa. Thus the product of the two values, [OH–] × [H3O+], is always 10–14 (moles/liter)2. A pure solution of water contains an equal con- centration (10–7 M) of both ions, rendering it neutral. The interior of a cell is also kept close to neutrality by the presence of buffers: weak acids and bases that can release or take up protons near pH 7, keeping the environment of the cell relatively constant under a variety of conditions. A Cell Is Formed from Carbon Compounds Having briefly reviewed the ways that atoms combine into molecules and how these molecules behave in an aqueous environment, we now examine the main classes of small molecules found in cells. We shall see that a few catego- ries of molecules, formed from a handful of different elements, give rise to all the extraordinary richness of form and behavior shown by living things. If we disregard water and inorganic ions such as potassium, nearly all the mole- cules in a cell are based on carbon. Carbon is outstanding among all the elements in its ability to form large molecules; silicon is a poor second. Because carbon is small and has four electrons and four vacancies in its outermost shell, a carbon atom can form four covalent bonds with other atoms. Most important, one carbon atom can join to other carbon atoms through highly stable covalent C–C bonds to form chains and rings and hence generate large and complex molecules with no obvious upper limit to their size. The carbon compounds made by cells are called organic molecules. In contrast, all other molecules, including water, are said to be inorganic. Certain combinations of atoms, such as the methyl (–CH3), hydroxyl (–OH), carboxyl (–COOH), carbonyl (–C O), phosphate (–PO32–), sulfhydryl (–SH), and amino (–NH2) groups, occur repeatedly in the molecules made by cells. Each such chemical group has distinct chemical and physical properties that influence the behavior of the molecule in which the group occurs. The most common chemical groups and some of their properties are summarized in Panel 2–1 (pp. 94–95). Cells Contain Four Major Families of Small Organic Molecules The small organic molecules of the cell are carbon-based compounds that have masses in the range of 100–1000 daltons and contain up to 30 or so carbon atoms. They are usually found free in solution and have many different fates. Some are used as monomer subunits to construct the giant polymeric macromolecules that make up most of the mass of the cell—proteins, nucleic acids, and large poly- saccharides. Others act as energy sources and are broken down and transformed into other small molecules in a maze of intracellular metabolic pathways. Many small molecules have more than one role in the cell; for example, acting both as a potential subunit for a macromolecule and as an energy source. Small organic molecules account for only about one-tenth of the total mass of organic matter in a cell, but they are very diverse. Nearly 4000 different kinds of small organic molecules have been detected in the well-studied bacterium, Escherichia coli. All organic molecules are synthesized from and are broken down into the same set of simple compounds. As a consequence, the compounds in a cell are MBOC7_ptr_ch02_049-114.indd 53 08/12/21 11:24 AM  54 Chapter 2: Cell Chemistry and Bioenergetics CH2OH small organic building blocks larger organic molecules C O of the cell of the cell H OH H H + POLYSACCHARIDES, GLYCOGEN, C C SUGARS OH H H3N C COO AND STARCH (IN PLANTS) HO H FATTY ACIDS FATS AND MEMBRANE LIPIDS C C CH3 H OH AMINO ACIDS PROTEINS A SUGAR AN AMINO ACID NUCLEOTIDES NUCLEIC ACIDS H H H H H H H H H H H H H H O H C C C C C C C C C C C C C C C _ Figure 2–6 The four main families of small organic molecules in H H H H H H H H H H H H H H O cells. These small molecules form the monomeric building blocks, or A FATTY ACID subunits, for most of the macromolecules and other assemblies of the cell. Some, such as the sugars and the fatty acids, are also energy NH2 sources. Their structures are outlined here and shown in more detail in the Panels at the end of this chapter and in Chapter 3. N N O –O N N P O CH2 O O– OH OH A NUCLEOTIDE chemically related and most can be classified into a few distinct families. Broadly speaking, cells contain four major families of small organic molecules: the sugars, the fatty acids, the nucleotides, and the amino acids (Figure 2–6). Although many compounds present in cells do not fit into these categories, these four families of small organic molecules, together with the macromolecules made by linking them into long chains, account for a large fraction of the cell mass. Amino acids and the proteins that they form will be the subject of Chapter 3. A summary of the structures and properties of theMBoC7 remaining three families— e2.17/2.06 sugars, fatty acids, and nucleotides—is presented in Panels 2–4, 2–5, and 2–6, respectively (see pp. 100–105). The Chemistry of Cells Is Dominated by Macromolecules with Remarkable Properties By weight, macromolecules are the most abundant carbon-containing mole­ cules in a living cell (Figure 2–7). They are the principal components from which a cell is constructed, and they also determine the most distinctive properties of living organisms. The macromolecules in cells are polymers that are constructed inorganic ions (1%) bacterial small molecules (3%) cell phospholipid (2%) DNA (1%) 30% chemicals RNA (6%) CELL MACROMOLECULES VOLUME OF Figure 2–7 The distribution of molecules 2 × 10–12 cm3 in cells. The approximate composition of 70% protein (15%) a bacterial cell is shown by weight. The H 2O composition of an animal cell is similar, even though its volume is roughly 1000 times greater. Note that macromolecules dominate. The major inorganic ions include polysaccharide (2%) Na+, K+, Mg2+, Ca2+, and Cl–. MBOC7_ptr_ch02_049-114.indd 54 08/12/21 11:24 AM  THE CHEMICAL COMPONENTS OF A CELL 55 by covalently linking small organic molecules (called monomers) into long chains SUBUNIT MACROMOLECULE (Figure 2–8). They have remarkable properties that could not have been predicted from their simple constituents. sugar polysaccharide Proteins are abundant and spectacularly versatile, performing thousands of distinct functions in cells. Many proteins serve as enzymes, the catalysts that facilitate the many covalent bond-making and bond-breaking reactions that the amino protein cell needs. Enzymes catalyze all of the reactions in which cells extract energy acid from food molecules, for example. Other proteins are used to build structural components, such as tubulin, a protein that self-assembles to make the cell’s nucleotide nucleic acid long microtubules, or histones, proteins that compact the DNA in chromo- somes. Many proteins serve as signaling devices, producing networks that control Figure 2–8 Three families of macromolecules. Each is a polymer cell functions. Yet other proteins act as molecular motors to produce force and formed from small molecules (called movement, as for myosin in muscle. We shall describe the remarkable chemistry monomers) linked together by that underlies these diverse roles throughout this book. covalent bonds. There are two types of Although the chemical reactions that add subunits to each polymer are nucleic acid: RNA and DNA. different in detail for proteins, nucleic acids, and polysaccharides, they share important features. Each polymer grows by the addition of a monomer onto the end of a growing chain in a condensation reaction, in which one molecule of water is lost with each subunit added (Figure 2–9). The stepwise polymerization of monomers into a long chain is a simple way to manufacture a large, complex molecule, because the subunits are added by the same reaction performed over and over again by the same set of enzymes. Apart from some of the poly- saccharides, most macromolecules are made from a limited set of monomers that are slightly different from one another; for example, the 20 different amino MBoC7 m2.08/2.08 acids from which proteins are made. It is critical to life that the polymer chain is not assembled at random from these subunits; instead, the subunits are added in a precise order, or sequence. The elaborate mechanisms that allow enzymes to accomplish this task are described in detail in Chapters 5 and 6. Noncovalent Bonds Specify Both the Precise Shape of a Macromolecule and Its Binding to Other Molecules Most of the covalent bonds in a macromolecule allow rotation of the atoms they join, giving the polymer chain great flexibility. In principle, this allows a macro- molecule to adopt an almost unlimited number of shapes, or conformations, as random thermal energy causes the polymer chain to writhe and rotate. However, the shapes of most biological macromolecules are highly constrained because of the many weak noncovalent bonds that form between different parts of the same molecule. If these noncovalent bonds are formed in sufficient numbers, the polymer chain can strongly prefer one particular conformation, determined by the linear sequence of monomers in its chain. Most protein molecules and many of the small RNA molecules found in cells fold tightly into a highly preferred conformation in this way (Figure 2–10). The four types of noncovalent interactions important in biological molecules were presented earlier (see also Panel 2–3, pp. 98–99). In addition to folding biological macromolecules into unique shapes, they can also add up to create a strong attraction between two different molecules (see Figure 2–4). This form of H2O H2O A H + HO B A B A H + HO B CONDENSATION HYDROLYSIS energetically energetically unfavorable favorable Figure 2–9 Condensation and hydrolysis as opposite reactions. The macromolecules of the cell are polymers that are formed from subunits (or monomers) by a condensation reaction, and they are broken down by hydrolysis. The condensation reactions are all energetically unfavorable; thus, polymer formation requires an energy input, as will be described in the text. MBOC7_ptr_ch02_049-114.indd 55 08/12/21 11:24 AM  56 Chapter 2: Cell Chemistry and Bioenergetics Figure 2–10 Proteins and RNA molecules are folded into a particularly stable three-dimensional shape, or conformation. If the noncovalent bonds maintaining the stable conformation are disrupted, the molecule becomes a flexible chain that loses its biological activity. CONDITIONS THAT DISRUPT NONCOVALENT BONDS a stable folded unstructured conformation polymer chains molecular interaction provides for great specificity, inasmuch as the close multi- point contacts required for strong binding make it possible for a macromolecule to select out—through binding—just MBoC7 one ofe2.34/2.10 the many thousands of types of mole- cules present inside a cell. Moreover, because the strength of the binding depends on the number of noncovalent bonds that are formed, interactions of almost any affinity are possible—allowing rapid dissociation where appropriate. As we discuss next, binding of this type underlies all biological catalysis, making it possible for proteins to function as enzymes. In addition, noncovalent interactions allow macromolecules to be used to build larger structures, thereby forming intricate machines with multiple moving parts that perform such com- plex tasks as DNA replication and protein synthesis (Figure 2–11). Summary Living organisms are autonomous, self-propagating chemical systems. They are formed from a distinctive and restricted set of small carbon-based molecules that are essentially the same for every living species. Each of these small molecules is composed of a set of atoms linked to each other in a precise configuration through covalent bonds. The main categories are sugars, fatty acids, amino acids, and nucleotides. Most of the dry mass of a cell consists of macromolecules that have been pro- duced as linear polymers of amino acids (proteins) or nucleotides (DNA and RNA), covalently linked to each other in an exact order. Most of the protein molecules and many of the RNAs fold into a particular conformation that is determined SUBUNITS MACROMOLECULES MACROMOLECULAR covalent noncovalent ASSEMBLY bonds bonds amino acids RNA molecule ribosome globular nucleotides protein 30 nm Figure 2–11 Small molecules are covalently linked to form macromolecules, which in turn can assemble through noncovalent interactions to form large complexes. Small molecules, proteins, and a ribosome are drawn approximately to scale. Ribosomes are a central part of the machinery that the cell uses to make proteins: each ribosome is formed as a complex of about 90 macromolecules (protein and RNA molecules). MBoC7 e2.36/2.11 MBOC7_ptr_ch02_049-114.indd 56 08/12/21 11:24 AM  CATALYSIS AND THE USE OF ENERGY BY CELLS 57 (A) (B) (C) (D) (E) 20 nm 50 nm 10 µm 0.5 mm 20 mm by their sequence of subunits. This folding process creates unique surfaces, and it Figure 2–12 Biological structures are depends on a large set of weak attractions produced by noncovalent forces between highly ordered. Well-defined, ornate, and beautiful spatial patterns can be found atoms. These forces are of four types: electrostatic attractions, hydrogen bonds, at every level of organization in living van der Waals attractions, and an attraction between nonpolar groups caused by organisms. In order of increasing size: their hydrophobic expulsion from water. The same set of weak forces governs the (A) protein molecules in the coat of a virus specific binding of a macromolecule to both small molecules and other macro­ (a parasite that, although not technically alive, contains the same types of molecules molecules, producing the myriad associations between biological molecules as those found in living cells); (B) the that generate the structure and the chemistry of a cell. MBoC7 m2.12/2.12 regular array of microtubules seen in a cross section of a sperm tail; (C) surface CATALYSIS AND THE USE OF ENERGY BY CELLS contours of a pollen grain (a single cell); (D) cross section of a fern stem, showing One property of living things above all makes them seem almost miraculously the patterned arrangement of cells; and (E) a spiral arrangement of leaves in a different from nonliving matter: they create and maintain order in a universe succulent plant. (A, courtesy of Robert that is tending always to greater disorder (Figure 2–12). To create this order, Grant, Stéphane Crainic, and James M. the cells in a living organism must perform a never-ending stream of chemical Hogle; B, courtesy of Lewis Tilney; C, reactions. In some of these reactions, small organic molecules—amino acids, courtesy of Colin MacFarlane and Chris sugars, nucleo­tides, and lipids—are being taken apart or modified to supply Jeffree; D, courtesy of Jim Haseloff; E, courtesy of Aron van de Selenib.) the many other small molecules that the cell requires. In other reactions, small molecules are being used to construct an enormously diverse range of pro- teins, nucleic acids, and other macromolecules that endow living systems with all of their most distinctive properties. Each cell can be viewed as a tiny chemical factory, performing many millions of reactions every second. Cell Metabolism Is Organized by Enzymes The chemical reactions that a cell carries out would normally proceed at an appre- ciable rate only at much higher temperatures than those existing inside cells. For this reason, each reaction requires a specific boost in chemical reactivity. This requirement is crucial, because it allows the cell to control its chemistry. The con- trol is exerted through specialized biological catalysts. These are almost always proteins called enzymes, although RNA catalysts also exist, called ribozymes. Each enzyme accelerates, or catalyzes, just one of the many possible kinds of reactions that a particular molecule might undergo. Enzyme-catalyzed reactions are con- nected in series, so that the product of one reaction becomes the starting material, or substrate, for the next (Figure 2–13). Long linear reaction pathways are in turn linked to one another, forming a maze of interconnected reactions that enable the cell to survive, grow, and reproduce. molecule molecule molecule molecule molecule molecule ABBREVIATED AS A B C D E F catalysis by catalysis by catalysis by catalysis by catalysis by enzyme 1 enzyme 2 enzyme 3 enzyme 4 enzyme 5 Figure 2–13 How a set of enzyme-catalyzed reactions generates a metabolic pathway. Each enzyme catalyzes a particular chemical reaction, leaving the enzyme unchanged. In this example, a set of enzymes acting in series converts molecule A to molecule F, forming a metabolic pathway. (For a diagram of many of the reactions in a human cell, abbreviated as shown, see Figure 2–62.) MBoC7 m2.13/2.13 MBOC7_ptr_ch02_049-114.indd 57 08/12/21 11:24 AM  58 Chapter 2: Cell Chemistry and Bioenergetics useful forms of energy CATABOLIC ANABOLIC PATHWAYS PATHWAYS lost the many food molecules heat building blocks the many for biosynthesis molecules that form the cell Figure 2–14 Schematic representation of the relationship between catabolic and anabolic pathways in metabolism. Catabolism produces both the building blocks and the energy required for biosynthesis. As indicated, a major portion of the energy stored in the chemical bonds of food molecules is dissipated as heat. As also suggested in this diagram, the mass of food required by any organism that derives all of its energy from catabolism is much greater than the mass of the molecules that it can produce by anabolism. Two opposing streams of chemical reactions occur in cells: (1) the catabolic MBoC7 e3.02/2.14 pathways break down foodstuffs into smaller molecules, thereby generating both a useful form of energy for the cell and some of the small molecules that the cell needs as building blocks; (2) the anabolic, or biosynthetic, pathways use the small molecules plus the energy harnessed by catabolism to drive the synthesis of the many other molecules that form the cell. Together these two sets of reactions constitute the metabolism of the cell (Figure 2–14). The many details of cell metabolism form the traditional subject of biochem- istry. Most of these details need not concern us here. But the general principles by which cells obtain energy from their environment and use it to create order are central to cell biology. We begin with a discussion of why a constant input of energy is needed to sustain all living things. Biological Order Is Made Possible by the Release of Heat Energy from Cells The universal tendency of things to become disordered is a fundamental law of physics—the second law of thermodynamics—which states that in the universe or in any isolated system (a collection of matter that is completely isolated from the rest of the universe), the degree of disorder always increases. This law has such profound implications for life that we will restate it in several ways. For example, we can present the second law in terms of probability by stating that systems will change spontaneously toward those arrangements that have the greatest probability. If we consider a box of 100 coins all lying heads-up, a series of accidents that disturbs the box will tend to move the arrangement toward a mixture of 50 heads and 50 tails. The reason is simple: there is a huge number of possible arrangements of the individual coins in the mixture that can achieve the 50–50 result, but only one possible arrangement that keeps all of the coins oriented heads-up. Because the 50–50 mixture is therefore the most probable, we say that it is more “disordered.” For the same reason, it is a common experience that one’s living space will become increasingly disordered without intentional effort: the movement toward disorder is a spontaneous process, requiring a periodic effort to reverse it (Figure 2–15). The amount of disorder in a system can be quantified and expressed as the entropy of the system: the greater the disorder, the greater the entropy. Thus, another way to express the second law of thermodynamics is to say that systems will change spontaneously toward arrangements with greater entropy. Living cells—by surviving, growing, and forming complex organisms—are generating order and thus might appear to defy the second law of thermodynam- ics. How is this possible? The answer is that a cell is not an isolated system: it takes in energy from its environment in the form of the chemical bonds in food MBOC7_ptr_ch02_049-114.indd 58 08/12/21 11:24 AM  CATALYSIS AND THE USE OF ENERGY BY CELLS 59 “SPONTANEOUS“ REACTION Figure 2–15 An everyday illustration of as time elapses the spontaneous drive toward disorder. Reversing this tendency toward disorder requires an intentional effort and an input of energy: it is not spontaneous. In fact, from the second law of thermodynamics, we can be certain that the human intervention required will release enough heat to the environment to more than compensate for the reordering of the items in this room. ORGANIZED EFFORT REQUIRING ENERGY INPUT or as photons from the Sun (or even, as in some chemosynthetic bacteria, from inorganic molecules alone). It then uses this energy to generate order within itself. Critically, during the chemical reactions that generate order, the cell con- verts part of the energy it uses into heat. The heat is discharged into the cell’s MBoC7 m2.15/2.15 environment and disorders the surroundings. As a result, the total entropy—that of the cell plus its surroundings—increases, as demanded by the second law of thermodynamics. To understand the principles governing these energy conversions, think of a cell surrounded by a sea of matter representing the rest of the universe. As the cell lives and grows, it creates internal order. But it constantly releases heat energy as it synthesizes molecules and assembles them into cell structures. Heat is energy in its most disordered form—the random jostling of molecules. When the cell releases heat to the sea, it increases the intensity of molecular motions there (thermal motion)—thereby increasing the randomness, or disorder, of the sea. The second law of thermodynamics is satisfied because the increase in the amount of order inside the cell is always more than compensated for by an even greater decrease in order (increase in entropy) in the surrounding sea of matter (Figure 2–16). Where does the heat that the cell releases come from? Here we encounter another important law of thermodynamics. The first law of thermodynamics Figure 2–16 A simple thermodynamic analysis of a living cell. In the diagram on the left, the molecules of both the sea of matter cell cell and the rest of the universe (the sea of matter) are depicted in a relatively disordered state. In the diagram on the right, the cell has taken in energy from food molecules and released heat through reactions that order the molecules the cell contains. The heat released increases the disorder in the environment around the cell HEAT (depicted by jagged arrows and distorted molecules, indicating increased molecular motions caused by heat). As a result, if enough heat is released, the second law of thermodynamics—which states that the amount of disorder in the universe must always increase—is satisfied as the cell grows and divides. For a detailed increased disorder increased order discussion, see Panel 2–7 (pp. 106–107). MBOC7_ptr_ch02_049-114.indd 59 08/12/21 11:24 AM  60 Chapter 2: Cell Chemistry and Bioenergetics falling brick has Figure 2–17 Some interconversions raised brick kinetic energy between different forms of energy. has potential (A) We can use the height and weight of energy due heat is released the brick to predict exactly how much to pull of when brick hits the floor heat will be released when it hits the gravity floor. (B) The large amount of chemical- bond energy released when water (H2O) is formed from H2 and O2 is initially converted to very rapid thermal motions in the two new H2O molecules; however, collisions with other H2O molecules almost A potential energy due to position kinetic energy heat energy instantaneously spread this kinetic energy evenly throughout the surroundings (heat transfer), making the new H2O molecules indistinguishable from all the rest. (C) Through coupled processes + to be described later, cells can convert chemical-bond energy into kinetic energy to drive, for example, molecular motor two hydrogen oxygen gas rapid vibrations and heat dispersed to proteins; however, this occurs without gas molecules molecule rotations of two newly surroundings the intermediate conversion of chemical formed water molecules energy to electrical energy that a man- rapid molecular made appliance such as this fan requires. B chemical-bond energy in H2 and O2 motions in H2O heat energy (D) Some cells can also harvest the energy (kinetic energy) from sunlight to form chemical bonds via photosynthesis. battery fan motor – – + + wires fan C chemical-bond energy electrical energy kinetic energy sunlight chlorophyll chlorophyll molecule molecule in excited state photosynthesis D electromagnetic (light) energy high-energy electrons chemical-bond energy states that energy can be converted from one form to another, but that it cannot MBoC7 e3.06/2.17 be created or destroyed. Figure 2–17 illustrates some interconversions between different forms of energy. The amount of energy in different forms will change as a result of the chemical reactions inside the cell, but the first law tells us that the total amount of energy must always be the same. For example, an animal cell takes in foodstuffs and converts some of the energy present in the chemi- cal bonds between the atoms of these food molecules (chemical-bond energy) into the random thermal motion of molecules (heat energy)—it is this heat that keeps our bodies warm. The cell cannot derive any benefit from the heat energy it releases unless the heat-generating reactions inside the cell are directly linked to the processes that generate molecular order. It is the tight coupling of heat production to an increase in order that distinguishes the metabolism of a cell from the wasteful burning of fuel in a fire. Later, we illustrate how this coupling occurs. For now, it is sufficient to recognize this critical fact: a direct linkage of the “controlled burning” of food molecules to the generation of biological order MBOC7_ptr_ch02_049-114.indd 60 08/12/21 11:24 AM  CATALYSIS AND THE USE OF ENERGY BY CELLS 61 PHOTOSYNTHESIS CELLULAR RESPIRATION Figure 2–18 Photosynthesis and CO2 + H2O O2 + SUGARS SUGARS + O2 H2O + CO2 respiration as complementary processes in the living world. Photosynthesis O2 CO2 CO2 O2 converts the electromagnetic energy in sunlight into chemical-bond energy in sugars and other organic molecules. Plants, algae, and cyanobacteria obtain PLANTS SUGARS AND MOST H2O H2O the carbon atoms that they need for this ALGAE OTHER ORGANIC LIVING SOME BACTERIA MOLECULES ORGANISMS purpose from atmospheric CO2 and the hydrogen from water, producing sugars and releasing O2 gas as a by-product. ENERGY USEFUL CHEMICAL- The organic molecules produced by OF photosynthesis in turn serve as food for SUNLIGHT BOND ENERGY other organisms. Many of these organisms carry out aerobic respiration, a process that uses O2 to form CO2 from the same carbon atoms that had been taken up as CO2 and converted into sugars by photosynthesis. is required for cells to create and maintain an island of order in a universe In the process, the organisms that respire tending toward chaos. obtain the chemical-bond energy that they need to survive. MBoC7 m2.18/2.18 The first cells on Earth are thought Cells Obtain Energy by the Oxidation of Organic Molecules to have been capable of neither photosynthesis nor respiration (discussed All animal and plant cells are powered by energy stored in the chemical bonds in Chapter 14). However, photosynthesis of organic molecules, whether they are sugars that a plant has photosynthesized must have preceded respiration on Earth, as food for itself or the mixture of large and small molecules that an animal has because there is strong evidence that eaten. Organisms must extract this energy in usable form to live, grow, and repro- billions of years of photosynthesis were duce. In both plants and animals, energy is extracted from food molecules by required before O2 had been released in sufficient quantity to create an atmosphere a process of gradual oxidation, or controlled burning. rich in this gas. (Earth’s atmosphere Earth’s atmosphere contains a great deal of oxygen, and in the presence of currently contains 21% O2.) oxygen the most energetically stable form of carbon is CO2 and that of hydro- gen is H2O. A cell is therefore able to obtain energy from sugars or other organic molecules by allowing their carbon and hydrogen atoms to combine with oxygen to produce CO2 and H2O, respectively—a process called aerobic respiration. Photosynthesis (discussed in detail in Chapter 14) and respiration are comple- mentary processes (Figure 2–18). This means that the transactions between plants and animals are not all one way. Plants, animals, and microorganisms have existed together on this planet for so long that many of them have become an essential part of the others’ environments. The oxygen released by photosynthesis is consumed in the combustion of organic molecules during aerobic respiration. And some of the CO2 molecules that are fixed today into organic molecules by photosynthesis in a green leaf were yesterday released into the atmosphere by the respiration of an animal—or by the respiration of a fungus or bacterium decomposing dead organic matter. We therefore see that carbon utilization forms a huge cycle that involves the biosphere (all of the living organisms on Earth) as a whole (Figure 2–19). Similarly, atoms of nitrogen, phosphorus, and sulfur move between the living and nonliving worlds in cycles that involve plants, algae, animals, fungi, and bacteria. Figure 2–19 How carbon atoms cycle through the biosphere. Individual carbon atoms are incorporated into organic molecules of the living world by the photosynthetic activity of bacteria, CO2 in atmosphere and water algae, and plants. They pass to animals, microorganisms, and organic material in CELL RESPIRATION PHOTOSYNTHESIS soil and oceans in cyclic paths. CO2 is restored to the atmosphere when organic molecules are oxidized by cells during plants, algae, respiration or burned by humans as fossil bacteria fuels. In this diagram, the green arrow animals denotes an uptake of CO2, whereas a red arrow indicates CO2 release. As indicated in Chapter 1, the total FOOD biomass on Earth is estimated to contain CHAIN ∼550 gigatons (1015 grams) of carbon (Gt C), of which 450 Gt C are plants, 70 are humus and dissolved sediments and bacteria, 7 are archaea, and 2 are animals organic matter fossil fuels (see Figure 1–14). MBOC7_ptr_ch02_049-114.indd 61 08/12/21 11:24 AM  62 Chapter 2: Cell Chemistry and Bioenergetics FORMATION OF (A) A POLAR (B) H methane _ _ COVALENT _ e e BOND e H C H + + + + _ + e O H R partial partial positive negative X charge (δ+) charge (δ–) E atom 1 atom 2 oxidized molecule reduced I H methanol D D H C OH U Figure 2–20 Oxidation and reduction. (A) When two atoms form a polar covalent bond, the A H atom ending up with a greater share of electrons is said to be reduced, while the other atom C acquires a lesser share of electrons and is said to be oxidized. The reduced atom has acquired T H formaldehyde a partial negative charge (δ–) as the positive charge on the atomic nucleus is now more than T equaled by the total charge of the electrons surrounding it, and conversely, the oxidized atom C O I I has acquired a partial positive charge (δ+). (B) The single carbon atom of methane can be H converted to that of carbon dioxide by the successive replacement of its covalently bonded O O hydrogen atoms with oxygen atoms. With each step, electrons are shifted away from the carbon H formic acid N (as indicated by the changes in the amount of blue shading), and the carbon atom becomes C O N progressively more oxidized. Each of these steps is energetically favorable under the conditions present inside a cell. HO O C O Oxidation and Reduction Involve Electron Transfers carbon dioxide The cell does not oxidize organic molecules in one step, as occurs when organic material is burned in a fire. Through the use of enzyme catalysts, metabolism takes these molecules through a large number of reactions that only rarely involve the direct addition of oxygen. Before we consider some of these reactions and their purpose, we discuss what is meant by the process of oxidation. Oxidation refers to more than the addition of oxygen atoms; the term applies more generally to any reaction in which electrons are transferred from one atom to another. Oxidation in this sense refers to the MBoC7 e3.11/2.20 removal of electrons, and reduction—the converse of oxidation—means the addition of electrons. Thus, Fe2+ is oxidized if it loses an electron to become Fe3+, and a chlorine atom is reduced if it gains an electron to become Cl–. Because the number of electrons is conserved (no loss or gain) in a chemical reaction, oxidation and reduction always occur simultaneously; that is, if one molecule gains an electron in a reaction (reduction), a second molecule loses the electron (oxidation). When a sugar molecule is oxidized to CO2 and H2O, for example, the O2 molecules involved in forming H2O gain electrons and thus are said to have been reduced. Why is a “gain” of electrons referred to as a “reduction”? The term arose before anything was known about the movement of electrons. Originally, reduc- tion reactions involved a liberation of oxygen—for example, when metals are extracted from ores by heating—which caused the samples to become lighter; in other words, “reduced” in mass. It is important to recognize that the terms “oxidation” and “reduction” apply even when there is only a partial shift of electrons between atoms linked by a covalent bond (Figure 2–20). When a carbon atom becomes covalently bonded to an atom with a strong affinity for electrons, such as oxygen, chlorine, or sul- fur, for example, it gives up more than its equal share of electrons and forms a polar covalent bond. Because the positive charge of the carbon nucleus is now somewhat greater than the negative charge of its electrons, the atom acquires a partial positive charge and is said to be oxidized. Conversely, a carbon atom in a C–H linkage has slightly more than its share of electrons, and so it is said to be reduced. When a molecule in a cell picks up an electron (e–), it often picks up a proton + (H ) at the same time (protons being freely available in water). The net effect in this case is to add a hydrogen atom to the molecule. A + e– + H+ → AH Even though a proton plus an electron is involved (instead of just an electron), such hydrogenation reactions are reductions, and the reverse dehydrogenation MBOC7_ptr_ch02_049-114.indd 62 08/12/21 11:24 AM  CATALYSIS AND THE USE OF ENERGY BY CELLS 63 reactions are oxidations. It is especially easy to tell whether an organic molecule is being oxidized or reduced: reduction is occurring if its number of C–H bonds increases, whereas oxidation is occurring if its number of C–H bonds decreases (see Figure 2–20B). Cells use enzymes to catalyze the oxidation of organic molecules in small steps, through a sequence of reactions that allows useful energy to be harvested. We now need to explain how enzymes work and some of the constraints under which they operate. Enzymes Lower the Activation-Energy Barriers That Block Chemical Reactions Consider the reaction paper + O2 → smoke + ashes + heat + CO2 + H2O Once ignited, the paper burns readily, releasing to the atmosphere both energy as heat and water and carbon dioxide as gases. The reaction is irreversible, as the smoke and ashes never spontaneously retrieve these entities from the heated atmosphere and reconstitute themselves into paper. When the paper burns, its chemical energy is dissipated as heat—not lost from the universe, as energy can never be created or destroyed, but irretrievably dispersed in the chaotic random thermal motions of molecules. At the same time, the atoms and molecules of the paper become dispersed and disordered. In the language of thermodynamics, there has been a loss of free energy; that is, of energy that can be harnessed to do work or drive chemical reactions. This loss reflects a reduction of orderliness in the way the energy and molecules were stored in the paper. We shall discuss free energy in more detail shortly, but the general principle is clear enough intuitively: chemical reactions proceed spontaneously only in the direction that leads to a loss of free energy. In other words, the spontaneous direction for any reaction is the direction that goes “downhill,” where a “downhill” reaction is one that is energetically favorable. Although the most energetically favorable form of carbon under ordinary con- ditions is CO2, and that of hydrogen is H2O, a living organism does not disappear in a puff of smoke, and the paper book in your hands does not burst into flames. This is because the molecules both in the living organism and in the book are in a relatively stable state, and they cannot be changed to a state of lower energy with- Figure 2–21 The important principle out an input of energy; in other words, a molecule requires activation energy—a of activation energy. (A) Compound Y kick over an energy barrier—before it can undergo a chemical reaction that leaves (a reactant) is in a relatively stable state, it in a more stable state (Figure 2–21). In the case of a burning book, the activation and energy is required to conve