CAPÍTULO 3: ANÁLISIS Y DISEÑO DEL SISTEMA
3.7. Modelo de despliegue
3-29 Which of the following is NOT a crucial benefit of using enzymes to catalyze biological reactions?
(a) Enzymes are highly selective in which reactions they catalyze.
(b) Enzymes can drive an unfavorable reaction by coupling it to a favorable reaction, either directly or via activated carrier molecules.
(c) Enzymes make reactions occur faster than without catalysis.
(d) Enzymes change the equilibrium of a reaction to make it more favorable.
(e) The activity of enzymes can be modulated by inhibitors and other small molecules to respond to the needs of the cell at each moment.
3-30 Consider an analogy between reaction coupling and money. In a simple economy, barter provides a means of direct exchange of material goods. For example, the owner of a cow may have excess milk and need eggs, whereas a chicken owner has excess eggs and needs milk. Provided these two people are in close proximity and can communicate, they may exchange or barter eggs for milk. But in a more complex economy, money serves as a mediator for the exchanges of goods or services. For instance, the cow owner with excess milk may not need other goods until three months from now or may want goods from someone who does not need milk. In this case, the “energy” from providing milk to the economy can be temporarily “stored” as money, which is a form of “energy” used for many transactions in the economy. Using barter and money as analogies, describe two mechanisms that can serve to drive an unfavorable chemical reaction in the cell.
3-31 A common means of providing energy to an energetically unfavorable reaction in a cell is by
(a) generation of a higher temperature by the cell.
(b) transfer of a phosphate group from the substrate to ADP.
(c) enzyme catalysis of the reaction.
(d) coupling of ATP hydrolysis to the reaction.
(e) coupling of the synthesis of ATP to the reaction.
3-32 An anhydride formed between a carboxylic acid and a phosphate (Figure Q3-32A) is formed as a high-energy intermediate in some reactions in which ATP is used as the energy source. Arsenate mimics phosphate and can also be incorporated into a similar high-energy intermediate (Figure Q3-32B). The reaction profiles for the hydrolysis of these two high-energy intermediates are given in Figure Q3-32C. What is the effect of substituting arsenate for phosphate in this reaction?
Figure Q3-32
(a) It forms a high-energy intermediate of lower energy.
(b) It forms a high-energy intermediate of the same energy.
(c) It decreases the stability of the high-energy intermediate.
(d) It increases the stability of the high-energy intermediate.
(e) It has no effect on the stability of the high-energy intermediate.
3-33 You are studying a biochemical pathway that requires ATP as an energy source. To your dismay, the reactions soon stop, partly because the ATP is rapidly used up and partly because an excess of ADP builds up and inhibits the enzymes involved. You are about to give up when the following table from a biochemistry textbook catches your eye.
Hydrolysis reaction ∆∆∆∆G °°°°
ADP + phosphate –7.3 kcal/mole
pyrophosphate + H2O
enzyme D
2 phosphate –7 kcal/mole
glucose 6-phosphate + H2O enzyme E glucose + phosphate –3.3 kcal/mole
Which of the following reagents are most likely to revitalize your reaction?
(a) A vast excess of ATP
(b) Glucose 6-phosphate and enzyme E (c) Creatine phosphate and enzyme A (d) Pyrophosphate
(e) Pyrophosphate and enzyme D
3-34 Which of the following statements is TRUE?
(a) The oxidation of food molecules generates NAD+.
(b) NADH and NADPH are found in mutually exclusive parts of the cell.
(c) The ratio of NADPH:NADP+ is higher than the ratio of NADH:NAD+ because each molecule of NADPH is a stronger reducing agent than a molecule of NADH.
(d) Many enzymes can use NADPH and NADH interchangeably.
(e) One molecule of NADPH can cause the transfer of two hydrogen atoms.
3-35 Match the activated carrier molecules in List 1 with the groups they transfer, selected from List 2. Write the appropriate number beside each item in List 1.
List 1 List 2
A. ATP 1. –COO–
B. Acetyl CoA 2. e– and H+
C. NADPH 3. Glucose
D. Carboxylated biotin 4. –PO43–
E. S-adenosylmethionine 5. –CH3
6. Nucleotide
7. –COCH3
8. Amino acid
3-36 Which of the following processes must be coupled to an energetically favorable reaction in order to occur?
(a) Conversion of protein into amino acids
(b) Polymerization of amino acids into polypeptides (c) Conversion of glucose to carbon dioxide and water (d) Formation of a bilayer from phospholipids in water (e) The hydrolysis of ATP
3-37 The enzymes that catalyze the synthesis of macromolecules do not also catalyze their breakdown by hydrolysis because
(a) enzymes can catalyze reactions in only one direction.
(b) hydrolysis is not an energetically favorable reaction.
(c) the hydrolytic reaction is not the reverse of the reaction pathway that is used for biosynthesis.
(d) enzymes are destroyed immediately after synthesis is completed.
(e) biosynthesis proceeds more rapidly than hydrolysis.
3-38 The energy required for the addition of a C nucleotide subunit (CMP) to a growing polynucleotide chain is originally derived from the hydrolysis of ATP. Explain how this is achieved.
Answers
3-1 No, you will not weigh four pounds more the next morning because only a small portion of the mass of the food will form components of the body. Much of the mass of food is released as CO2 that is breathed out into the atmosphere or is released into the
environment as waste products. Most of the energy contained in the chemical bonds of the food molecules is converted to energy to maintain order among molecules in the body, energy to move and think, and energy for anabolic or biosynthetic reactions to rearrange the atoms from food into useful chemical structures (biological small molecules and macromolecules). As part of the process, a great deal of the bond energy is also converted to heat.
3-2 Choice (c) is the answer. Choice (a) is incorrect as no system, living or otherwise, can defy the laws of thermodynamics. Choice (b) is incorrect as living organisms do not use heat to power biochemical reactions. Heat is produced in the course of biochemical reactions. Choice (d) is incorrect: although living organisms are causing a local decrease in entropy, they cannot cause a decrease in the entropy of the universe as a whole as that would be a thermodynamic impossibility. Choice (e) is incorrect as living organisms are not closed systems.
3-3 (a) By releasing heat to their environment, living things increase the entropy of the environment, thus compensating for the decrease in entropy inside cells. Living things, therefore, satisfy the second law of thermodynamics. They use special pathways for all their reactions that allow them to be energetically favorable.
3-4 Choice (c) is the answer. Catabolic reactions are the reactions in which a cell breaks down food molecules, releasing the energy held within their chemical bonds. Choices (a), (b), and (e) are energy-requiring processes.
3-5 Choice (b) is true. Photosynthesis harvests light energy from the sun and converts it into chemical bond energy. Choice (a) is false because food molecules and oxygen produced by photosynthesis are the sole source of the energy that powers nearly all living non-photosynthetic organisms. Photosynthesis activates carrier molecules as intermediates in the “fixation” of inorganic carbon dioxide into organic sugar molecules (so choices (c) and (d) are false). By consuming carbon dioxide and producing oxygen photosynthesis lessens global warming cause by the greenhouse effect (choice (e) is false).
3-6 A. Sugars + O2 → CO2 + H2O + heat energy + chemical bond energy
B. Both respiration and burning are reactions that use oxygen gas to oxidize complex organic carbon molecules into CO2 + H2O. Burning is an uncontrolled oxidation in which the energy is all dissipated as heat; respiration is a multi-step, controlled oxidation that harnesses the energy in high-energy chemical bonds that are useful for anabolic reactions of cells.
3-7 A—ii; B—ii; C—i; D—ii. “More reduced” means having more electrons; gain of electrons can result in an increased negative charge or a decreased positive charge and can be due to an increase in the number of hydrogen atoms in a molecule.
3-8 A. True. A redox reaction involves the complete or partial transfer of electrons from one molecule or atom to another. The donor is oxidized and the recipient is reduced in the reaction.
B. False. Hydrogenation is a special kind of reduction reaction, involving receipt of an electron from a donor molecule and acquisition of a proton, usually from water. Hydrogenation increases the number of C-H bonds in a molecule.
C. True. The diameter of an atom is influenced by the amount of negative charge, or electron density, surrounding it. The more reduced an atom becomes, the larger will be its electron cloud.
3-9 By definition, catalysis allows a reaction to occur more rapidly. Chemical reactions occur only when there is a loss of free energy. Enzymes act more selectively than other catalysts. A catalyst reduces the activation energy of a reaction.
3-10 (d) 3-11 (b)
3-12 (d) Enzymes change only the activation energy of a reaction, not the free energy difference between reactants and products and thus cannot change the equilibrium concentrations of reactants and products.
3-13 See Figure A3-13.
Figure A3-13 A. Activation energy is (a minus b).
B. Change in free energy for the reaction is (b minus c).
C. An enzyme will make the value of (a) smaller and leave the values for (b) and (c) unchanged.
3-14 (d)
3-15 A. (a) and (c). Only reactions with a negative ∆G can occur spontaneously.
B. Coupling of reaction (d) to either of the reactions (a) or (c) would provide an overall negative ∆G for the coupled reactions, thus enabling them to occur.
3-16 A—2; B—3; C—1; D—4. Graph 4 is the same as the graph for the original reaction in terms of the relative energetic differences between substrates, transition states, and products; the reaction diagram curve is simply positioned higher on the y-axis.
3-17 Choice (a) is correct. The value of ∆G for the reaction A ⇔ B is zero when there is no net tendency for either A → B or B → A, which is the definition of equilibrium. ∆G° is a constant and is thus always the same regardless of whether the reaction has reached equilibrium or not. Thus choices (b) and (d) are incorrect. Choice (c) is an incorrect answer; although a particular reaction might be at equilibrium when the concentration of substrate equals that of product, this is not true for most reactions. Choice (e) is not a definition of equilibrium, but of a reaction that is not occurring at all.
3-18 A. Keq = [Y]/[X] = 5 µM/50 µM = 0.1.
B. The standard free energy change, ∆G°, is positive because Keq is less than 1.
Under standard conditions (equal concentrations of X and Y), the reaction X → Y is unfavorable.
C. ∆G° = –0.616 ln Keq = –0.616 ln 0.1 = (–0.616) (–2.3) = 1.4 kcal/mol.
D. Yes, the conversion is favorable because the value of [Y]/[X] is less than the equilibrium value. However, the speed of the reaction cannot be determined from the free energy difference. For example, combustion of this piece of paper is a highly favorable reaction, yet it will not happen in our lifetime without a catalyst.
E. The cell may directly couple the unfavorable reaction to a second, energetically favorable reaction whose negative ∆G has a value larger than the positive ∆G of the X → Y reaction; the coupled reaction will have a ∆G equal to the sum of the component reactions. Alternatively, more X will be converted to Y if the concentration of Y drops; this may happen if Y is converted to Z in a second reaction or if Y is exported from the cell or compartment where the X → Y reaction occurs.
3-19 (b) The equilibrium constant measures the strength of the interaction between a protein and its ligand and is independent of the concentration of either the protein or the ligand. The strength of the protein-ligand interaction increases as the number of noncovalent bonds between the two increases. The shape of the binding site affects the ability of the protein side chains to interact with portions of the substrate molecule. Both temperature and pH can disrupt noncovalent bonds that not only affect the binding, but are also responsible for keeping the protein folded and thus functional.
3-20 Choice (c) is true. The binding energy is the standard free energy of the binding reaction, and thus is proportional to ln Keq. As the binding energy increases, the equilibrium constant for the association reaction becomes larger. Choices (a) and (b) are false, because although E binds S more tightly than it does I, some E molecules will still be bound to I molecules in most circumstances; indeed, if the number of I molecules far exceeds the number of S molecules, more E molecules will be present in an EI complex than in an ES complex. Choice (d) is false; although not enough information is given to be certain, it is likely that binding is normally strengthened by an ionic interaction between a basic amino acid in I and an acidic amino acid in E—thus, if anything, the binding energy will be reduced by the amino acid change and the free energy change will be less (not more) negative. Choice (e) is false, because although the association of two molecules often does decrease their own entropy, it can increase the entropy of other molecules in the system. For example, heat release by the binding reaction can increase the entropy of the system and its surroundings.
3-21 (c) Reaction 1 can be written as the sum of the three reactions given, since the ATP used in Step 2 is restored in Step 3.
X-X-X... + H2O → X + X-X... ∆G° = –4.5 kcal/mole
X + ATP → X-P + ADP ∆G° = –2.8 kcal/mole
ADP + P → ATP + H2O ∆G° = +7.3 kcal/mole
Since ∆G° values are additive, ∆G°total = 0, and if ∆G° = 0, Keq = 1, meaning that [products]/[reactants] = 1, and the ratio of X-P to P is 1:1.
3-22 (b) The constant removal of CO2 and replenishment of O2 by the blood normally drives the reaction Y → Z. Therefore, when CO2 is allowed to accumulate and O2
drops, Y will accumulate. Because the ∆G° of the first reaction is very negative, Y can accumulate to a very high level without causing significant amounts of X to build up.
3-23 A. See Figure A3-23 for correct labeling of figure.
Figure A3-23 B. Favorable
3-24 A. Graph 1
B. By increasing thermal motion, increasing the temperature increases the rate of diffusion of components and the number of collisions of sufficient energy to overcome the activation energy. An increase in temperature will thus increase the reaction rate initially. However, enzymes are proteins and are held together by noncovalent interactions, so at very high temperatures, the enzyme will begin to denature and the reaction rate will fall.
3-25 A. False. The diffusion rate is almost as fast in the cytoplasm and in water.
B. False. The diffusion coefficient of a molecule decreases with increasing mass (shape is also a factor).
C. False. Although some binding reactions are diffusion-limited, others require an unusually energetic collision to overcome an energy barrier.
D. False. The diffusion rate influences how often an enzyme will encounter (and thus bind) its substrate.
E. False. Diffusing molecules move in a “random walk,” in which they change direction frequently after colliding with other molecules.
3-26 Choices (a), (c), and (d) are correct. The higher the concentration and diffusion rate of substrate, the more frequently a free enzyme will collide with and bind its substrate. The less tightly an enzyme binds its product, in general, the faster the product will dissociate from the enzyme, leaving it free to bind a fresh substrate. Choice (b) is incorrect because a more positive free energy of binding indicates it is less energetically favorable and thus occurs less often. Choice (e) is likely to be false because many enzyme-substrate binding interactions rely on ionic bonds that are weakened by high salt concentrations; in
addition, high salt concentrations can distort protein conformations.
3-27 A. True
Thus, half of the enzyme molecules are free and half are bound to the substrate.
B. Yes. If half of the enzyme molecules are bound to the substrate, it makes intuitive sense that the reaction rate is half of the maximum possible rate or half of the rate observed when all of the enzyme molecules are bound to the substrate.
3-29 (d) Enzymes cannot change the equilibrium of a reaction.
3-30 Barter is analogous to the direct coupling of a favorable to an unfavorable reaction by a single enzyme. Money is analogous to the storage of energy from a favorable reaction in the form of high-energy bonds in an activated carrier molecule. Such activated carrier molecules can drive a huge variety of other unfavorable reactions in the cell, either by being hydrolyzed to provide the needed energy for a reaction or by transferring the activated chemical group to another molecule.
3-31 (d)
3-32 Choice (c) is correct. The activation energy of the arsenate compound is extremely low, as can be seen from the reaction profile, meaning that its high-energy intermediate is very unstable and will be spontaneously hydrolyzed more rapidly than the phosphate
compound. In fact, this hydrolysis occurs rapidly without enzyme catalysis, even in cellular conditions. Thus choices (d) and (e) are false. Choices (a) and (b) are false as more energy is released by the hydrolysis of the arsenoanhydride bond (as inferred by the greater difference in energy level between reactants and products in Figure Q3-32) so, by definition, the arsenoanhydride bond is said to have more energy than the
phosphoanhydride bond.
3-33 (c) An excess of ATP will initially restore the reactions, but as ATP is hydrolyzed, ADP will build up and inhibit the enzymes again. Pyrophosphate does not look like ATP and is therefore unlikely to be used by the enzymes as an alternative energy source. Pyrophosphate + enzyme D will just heat things up. What you need is a high-energy source of phosphate that can convert ADP back to ATP.
Since the ∆G° of the reaction,
ATP + creatine → ADP + creatine phosphate,
catalyzed by enzyme A is greater than zero, the addition of creatine phosphate and enzyme A can be used to form ATP from ADP, regenerating the ATP while also forming creatine as a waste product.
3-34 Choice (e) is correct. NADPH has two electrons and one proton more than NADP+ (like NADH compared to NAD+) and donates both electrons. Protons are always present in solution. So the recipient molecule effectively acquires two hydrogen atoms. Choice (a) is false because oxidation of food molecules produces NADH, not NAD+. Chioce (b) is false because NADH and NADPH can be found in the same parts of the cell, but are used for different functions; this is possible because the enzymes that recognize one do not recognize the other; thus choice (d) is also false. Choice (c) is false because the parts of NADPH and NADH that participate in reduction are identical, and thus they both have essentially the same reducing power.
3-35 A—4 (phosphate group); B—7 (acetyl group); C—2; D—1 (carboxyl group); E—5 (methyl group).
3-36 (b) Polymerization of amino acids into polypeptides lead to the formation of peptide bonds that have higher energy than the free amino acids and also represents an increase in order. Hence, it can only be brought about via an input of energy. The other processes are thermodynamically spontaneous.
3-37 (c) Hydrolysis is not the reverse of the reactions catalyzed by biosynthetic enzymes.
For instance, the reactions involved in RNA biosynthesis are:
polynucleotide(n) + NTP → polynucleotide(n + 1) + PPi PPi + H2O → 2 Pi.
The reverse reactions are:
2 Pi → PPi + H2O
PPi + polynucleotide(n + 1) → polynucleotide(n) + NTP, Not:
polynucleotide(n + 1) + H2O → polynucleotide(n) + NMP (nucleoside
monophosphate), which is the reaction by which RNA is hydrolyzed. (a) and (b) are untrue:
enzymes catalyze both forward and reverse reactions, and hydrolysis is an energetically favorable reaction. (d) is untrue, since enzymes are unchanged by participating in catalysis. Whether (e) is true or not for any particular reaction is irrelevant.
3-38 In order to add the C nucleotide to the polynucleotide chain, it must be in the form of a CTP (cytidine triphosphate). Conversion of CMP to CTP occurs by the sequential
transfer of two terminal phosphate groups from two molecules of ATP. Thus, hydroylysis of ATP is coupled to phosphorylation of CMP and then to phosphorylation of CDP.
Subsequently, the reaction that adds CMP to the polynucleotide chain releases
pyrophosphate (PPi), which is hydrolyzed to inorganic phosphate; this favorable reaction provides the energetic drive for the overall condensation (or polymerization) reaction.
C HAPTER 4