HOW CELLS OBTAIN ENERGY FROM FOOD. Summary HOW CELLS OBTAIN ENERGY FROM FOOD

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1 3 EAD LYMERIZATIN (e.g., RTEINS, FATTY AIDS) TAIL LYMERIZATIN (e.g., DNA, RNA, LYSAARIDES) each monomer carries a high-energy bond that will be used for the addition of the next monomer each monomer carries a high-energy bond for its own addition 1 growing polymer, and it must therefore be regenerated each time that a monomer is added. In this case, each monomer brings with it the reactive bond that will be used in adding the next monomer in the series. In tail polymerization, the reactive bond carried by each monomer is instead used immediately for its own addition (Figure 2 44). We shall see in later chapters that both of these types of polymerization are used. The synthesis of polynucleotides and some simple polysaccharides occurs by tail polymerization, for example, whereas the synthesis of proteins occurs by a head polymerization process. Figure 2 44 The orientation of the active intermediates in the repetitive condensation reactions that form biological polymers. The head growth of polymers is compared with its alternative, tail growth. As indicated, these two mechanisms are used to produce different types of biological macromolecules. Summary Living cells need to create and maintain order within themselves to survive and grow. This is thermodynamically possible only because of a continual input of energy, part of which must be released from the cells to their environment as heat that disorders the surroundings. The only chemical reactions possible are those that increase the total amount of disorder in the universe. The free-energy change for a reaction, G, measures this disorder, and it must be less than zero for a reaction to proceed spontaneously. This G depends both on the intrinsic properties of the reacting molecules and their concentrations, and it can be calculated from these concentrations if either the equilibrium constant (K) for the reaction or its standard free-energy change, G, is known. The energy needed for life comes ultimately from the electromagnetic radiation of the sun, which drives the formation of organic molecules in photosynthetic organisms such as green plants. Animals obtain their energy by eating organic molecules and oxidizing them in a series of enzyme-catalyzed reactions that are coupled to the formation of a common currency of energy in all cells. To make possible the continual generation of order in cells, energetically favorable reactions, such as the hydrolysis of, are coupled to energetically unfavorable reactions. In the biosynthesis of macromolecules, is used to form reactive phosphorylated intermediates. Because the energetically unfavorable reaction of biosynthesis now becomes energetically favorable, hydrolysis is said to drive the reaction. olymeric molecules such as proteins, nucleic acids, and polysaccharides are assembled from small activated precursor molecules by repetitive condensation reactions that are driven in this way. ther reactive molecules, called either activated carriers or coenzymes, transfer other chemical groups in the course of biosynthesis: transfers hydrogen as a proton plus two electrons (a hydride ion), for example, whereas acetyl oa transfers an acetyl group. The constant supply of energy that cells need to generate and maintain the biological order that keeps them alive comes from the chemical-bond energy in food molecules. The proteins, lipids, and polysaccharides that make up most of the food we eat must be broken down into smaller molecules before our cells can use them either

2 4 hapter 2: ell hemistry and Bioenergetics as a source of energy or as building blocks for other molecules. Enzymatic digestion breaks down the large polymeric molecules in food into their monomer subunits proteins into amino acids, polysaccharides into sugars, and fats into fatty acids and glycerol. After digestion, the small organic molecules derived from food enter the cytosol of cells, where their gradual oxidation begins. Sugars are particularly important fuel molecules, and they are oxidized in small controlled steps to carbon dioxide ( 2 ) and water (Figure 2 45). In this section, we trace the major steps in the breakdown, or catabolism, of sugars and show how they produce,, and other activated carrier molecules in animal cells. A very similar pathway also operates in plants, fungi, and many bacteria. As we shall see, the oxidation of fatty acids is equally important for cells. ther molecules, such as proteins, can also serve as energy sources when they are funneled through appropriate enzymatic pathways. Glycolysis Is a entral -roducing athway The major process for oxidizing sugars is the sequence of reactions known as glycolysis from the Greek glukus, sweet, and lusis, rupture. Glycolysis produces without the involvement of molecular oxygen ( 2 gas). It occurs in the cytosol of most cells, including many anaerobic microorganisms. Glycolysis probably evolved early in the history of life, before photosynthetic organisms introduced oxygen into the atmosphere. During glycolysis, a glucose molecule with six carbon atoms is converted into two molecules of pyruvate, each of which contains three carbon atoms. For each glucose molecule, two molecules of are hydrolyzed to provide energy to drive the early steps, but four molecules of are produced in the later steps. At the end of glycolysis, there is consequently a net gain of two molecules of for each glucose molecule broken down. Two molecules of the activated carrier are also produced. The glycolytic pathway is outlined in Figure 2 46 and shown in more detail in anel 2 8 (pp ) and Movie 2.5. Glycolysis involves a sequence of 10 separate reactions, each producing a different sugar intermediate and each catalyzed by a different enzyme. Like most enzymes, these have names ending in ase such as isomerase and dehydrogenase to indicate the type of reaction they catalyze. Although no molecular oxygen is used in glycolysis, oxidation occurs, in that electrons are removed by (producing ) from some of the carbons derived from the glucose molecule. The stepwise nature of the process releases the energy of oxidation in small packets, so that much of it can be stored in activated carrier molecules rather than all of it being released as heat (see Figure 2 45). Thus, some of the energy released by oxidation drives the direct synthesis of molecules from AD and i, and some remains with the electrons in the electron carrier. Figure 2 45 Schematic representation of the controlled stepwise oxidation of sugar in a cell, compared with ordinary burning. (A) If the sugar were oxidized to 2 and 2 in a single step, it would release an amount of energy much larger than could be captured for useful purposes. (B) In the cell, enzymes catalyze oxidation via a series of small steps in which free energy is transferred in conveniently sized packets to carrier molecules most often and. At each step, an enzyme controls the reaction by reducing the activation-energy barrier that has to be surmounted before the specific reaction can occur. The total free energy released is exactly the same in (A) and (B). (A) DIRET BURNING F SUGAR IN NNLIVING SYSTEM (B) STEWISE XIDATIN F SUGAR IN ELLS SUGAR + 2 large activation energy overcome by the heat from a fire SUGAR + 2 small activation energies overcome by enzymes that work at body temperature free energy all free energy is released as heat; none is stored some free energy stored in activated carrier molecules

3 5 Two molecules of are formed per molecule of glucose in the course of glycolysis. In aerobic organisms, these molecules donate their electrons to the electron-transport chain described in hapter 14, and the formed from the is used again for glycolysis (see step 6 in anel 2 8, pp ). Fermentations roduce in the Absence of xygen For most animal and plant cells, glycolysis is only a prelude to the final stage of the breakdown of food molecules. In these cells, the pyruvate formed by glycolysis is rapidly transported into the mitochondria, where it is converted into 2 plus acetyl oa, whose acetyl group is then completely oxidized to 2 and 2. In contrast, for many anaerobic organisms which do not utilize molecular oxygen and can grow and divide without it glycolysis is the principal source of the cell s. ertain animal tissues, such as skeletal muscle, can also continue to function when molecular oxygen is limited. In these anaerobic conditions, the pyruvate and the electrons stay in the cytosol. The pyruvate is converted into products excreted from the cell for example, into ethanol and 2 in the yeasts used in brewing and breadmaking, or into lactate in muscle. In this process, the gives up its electrons and is converted back into. This regeneration of is required to maintain the reactions of glycolysis (Figure 2 4). Energy-yielding pathways like these, in which organic molecules both donate and accept electrons (and which are often, as in these cases, anaerobic), are called 2 one molecule of glucose STE 1 energy investment to be recouped later STE 2 STE 3 fructose 1,6- bisphosphate 2 2 STE 4 STE 5 cleavage of six-carbon sugar to two three-carbon sugars two molecules of glyceraldehyde 3-phosphate 2 2 two molecules of pyruvate STE 6 STE STE 8 STE 9 STE 10 energy generation Figure 2 46 An outline of glycolysis. Each of the 10 steps shown is catalyzed by a different enzyme. Note that step 4 cleaves a six-carbon sugar into two threecarbon sugars, so that the number of molecules at every stage after this doubles. As indicated, step 6 begins the energygeneration phase of glycolysis. Because two molecules of are hydrolyzed in the early, energy-investment phase, glycolysis results in the net synthesis of 2 and 2 molecules per molecule of glucose (see also anel 2 8).

4 6 hapter 2: ell hemistry and Bioenergetics (A) FERMENTATIN LEADING T EXRETIN F LATATE AD glucose glycolysis pyruvate + + regeneration lactate Figure 2 4 Two pathways for the anaerobic breakdown of pyruvate. (A) When there is inadequate oxygen, for example, in a muscle cell undergoing vigorous contraction, the pyruvate produced by glycolysis is converted to lactate as shown. This reaction regenerates the consumed in step 6 of glycolysis, but the whole pathway yields much less energy overall than complete oxidation. (B) In some organisms that can grow anaerobically, such as yeasts, pyruvate is converted via acetaldehyde into carbon dioxide and ethanol. Again, this pathway regenerates from, as required to enable glycolysis to continue. Both (A) and (B) are examples of fermentations. (B) FERMENTATIN LEADING T EXRETIN F ETANL AND 2 glucose AD glycolysis regeneration 2 pyruvate 2 acetaldehyde ethanol fermentations. Studies of the commercially important fermentations carried out by yeasts inspired much of early biochemistry. Work in the nineteenth century led in 1896 to the then startling recognition that these processes could be studied outside living organisms, in cell extracts. This revolutionary discovery eventually made it possible to dissect out and study each of the individual reactions in the fermentation process. The piecing together of the complete glycolytic pathway in the 1930s was a major triumph of biochemistry, and it was quickly followed by the recognition of the central role of in cell processes. Glycolysis Illustrates ow Enzymes ouple xidation to Energy Storage The formation of during glycolysis provides a particularly clear demonstration of how enzymes couple energetically unfavorable reactions with favorable ones, thereby driving the many chemical reactions that make life possible. Two central reactions in glycolysis (steps 6 and ) convert the three-carbon sugar intermediate glyceraldehyde 3-phosphate (an aldehyde) into 3-phosphoglycerate (a carboxylic acid; see anel 2 8, pp ), thus oxidizing an aldehyde group to a carboxylic acid group. The overall reaction releases enough free energy to convert a molecule of AD to and to transfer two electrons (and a proton) from the aldehyde to to form, while still liberating enough heat to the environment to make the overall reaction energetically favorable ( G for the overall reaction is 12.5 kj/mole). Figure 2 48 outlines this remarkable feat of energy harvesting. The chemical reactions are precisely guided by two enzymes to which the sugar intermediates

5 glyceraldehyde 3-phosphate dehydrogenase STE 6 S (A) STES 6 AND F GYLYSIS ENZYME ENZYME ENZYME high-energy phosphate bond 2 S 2 S glyceraldehyde 3-phosphate high-energy thioester bond i inorganic phosphate A short-lived covalent bond is formed between glyceraldehyde 3-phosphate and the S group of a cysteine side chain of the enzyme glyceraldehyde 3-phosphate dehydrogenase. The enzyme also binds noncovalently to. Glyceraldehyde 3-phosphate is oxidized as the enzyme removes a hydrogen atom (yellow) and transfers it, along with an electron, to, forming (see Figure 2 3). art of the energy released by the oxidation of the aldehyde is thus stored in, and part is stored in the highenergy thioester bond that links glyceraldehyde 3-phosphate to the enzyme. A molecule of inorganic phosphate displaces the high-energy thioester bond to create 1,3-bisphosphoglycerate, which contains a high-energy phosphate bond. Figure 2 48 Energy storage in steps 6 and of glycolysis. (A) In step 6, the enzyme glyceraldehyde 3-phosphate dehydrogenase couples the energetically favorable oxidation of an aldehyde to the energetically unfavorable formation of a high-energy phosphate bond. At the same time, it enables energy to be stored in. The formation of the high-energy phosphate bond is driven by the oxidation reaction, and the enzyme thereby acts like the paddle wheel coupler in Figure 2 32B. In step, the newly formed high-energy phosphate bond in 1,3-bisphosphoglycerate is transferred to AD, forming a molecule of and leaving a free carboxylic acid group on the oxidized sugar. The part of the molecule that undergoes a change is shaded in blue; the rest of the molecule remains unchanged throughout all these reactions. (B) Summary of the overall chemical change produced by reactions 6 and. 1,3-bisphosphoglycerate 2 phosphoglycerate kinase STE A AD A The high-energy phosphate group is transferred to AD to form. 2 3-phosphoglycerate (B) SUMMARY F STES 6 AND aldehyde carboxylic acid The oxidation of an aldehyde to a carboxylic acid releases energy, much of which is captured in the activated carriers and.

6 8 hapter 2: ell hemistry and Bioenergetics are tightly bound. As detailed in Figure 2 48, the first enzyme (glyceraldehyde 3-phosphate dehydrogenase) forms a short-lived covalent bond to the aldehyde through a reactive S group on the enzyme, and catalyzes its oxidation by in this attached state. The reactive enzyme substrate bond is then displaced by an inorganic phosphate ion to produce a high-energy phosphate intermediate, which is released from the enzyme. This intermediate binds to the second enzyme (phosphoglycerate kinase), which catalyzes the energetically favorable transfer of the high-energy phosphate just created to AD, forming and completing the process of oxidizing an aldehyde to a carboxylic acid. Note that the bond oxidation energy in step 6 drives the formation of both and a high-energy phosphate bond. The breakage of the high-energy bond then drives formation. We have shown this particular oxidation process in some detail because it provides a clear example of enzyme-mediated energy storage through coupled reactions (Figure 2 49). Steps 6 and are the only reactions in glycolysis that create a high-energy phosphate linkage directly from inorganic phosphate. As such, they account for the net yield of two molecules and two molecules per molecule of glucose (see anel 2 8, pp ). As we have just seen, can be formed readily from AD when a reaction intermediate is formed with a phosphate bond of higher energy than the terminal phosphate bond in. hosphate bonds can be ordered in energy by comparing the standard free-energy change ( G ) for the breakage of each bond by hydrolysis. Figure 2 50 compares the high-energy phosphoanhydride bonds in with the energy of some other phosphate bonds, several of which are generated during glycolysis. rganisms Store Food Molecules in Special Reservoirs All organisms need to maintain a high /AD ratio to maintain biological order in their cells. Yet animals have only periodic access to food, and plants need to survive overnight without sunlight, when they are unable to produce sugar from photosynthesis. For this reason, both plants and animals convert sugars and fats to special forms for storage (Figure 2 51). To compensate for long periods of fasting, animals store fatty acids as fat droplets composed of water-insoluble triacylglycerols (also called triglycerides). The triacylglycerols in animals are mostly stored in the cytoplasm of specialized fat cells called adipocytes. For shorter-term storage, sugar is stored as glucose 1,3-bisphosphoglycerate formation of high-energy bond hydrolysis of high-energy bond free energy AD bond oxidation glyceraldehyde 3-phosphate 3-phosphoglycerate TTAL ENERGY ANGE for step 6 followed by step is a favorable 12.5 kj/mole STE 6 STE Figure 2 49 Schematic view of the coupled reactions that form and in steps 6 and of glycolysis. The bond oxidation energy drives the formation of both and a high-energy phosphate bond. The breakage of the highenergy bond then drives formation.