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An Introduction to Metabolism

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1 An Introduction to Metabolism

2 How do living organisms create macromolecules, organelles, cells, tissues, and complex higher-order structures? The laws of thermodynamics do not apply to living organisms. Living organisms create order by recycling and reusing energy from the sun. Living organisms create order locally, but the energy transformations generate waste heat that increases the entropy of the universe. Answer: C

3 How do living organisms create macromolecules, organelles, cells, tissues, and complex higher-order structures? The laws of thermodynamics do not apply to living organisms. Living organisms create order by recycling and reusing energy from the sun. Living organisms create order locally, but the energy transformations generate waste heat that increases the entropy of the universe. 3

4 Entropy can drive a chemical reaction; for example,
A  B  C B  C  A  D A  B  C  D A  B  C  D  E  F A  B Answer: A 4

5 Entropy can drive a chemical reaction; for example,
A  B  C B  C  A  D A  B  C  D A  B  C  D  E  F A  B 5

6 Are most chemical reactions at equilibrium in living cells?
yes no only the exergonic reactions all reactions except those powered by ATP hydrolysis Answer: B At equilibrium, the free-energy change is zero, and no work can be done. A cell at equilibrium is dead! 6

7 Are most chemical reactions at equilibrium in living cells?
yes no only the exergonic reactions all reactions except those powered by ATP hydrolysis 7

8 A reaction has a G of 5. 6 kcal/mol
A reaction has a G of 5.6 kcal/mol. Which of the following would most likely be true? The reaction could be coupled to power an endergonic reaction with a G of 8.8 kcal/mol. The reaction is nonspontaneous. To take place, the reaction would need to couple to ATP hydrolysis. The reaction would result in products with a greater free-energy content than in the initial reactants. The reaction would proceed by itself but might be very slow. Answer: E 8

9 A reaction has a G of 5. 6 kcal/mol
A reaction has a G of 5.6 kcal/mol. Which of the following would most likely be true? The reaction could be coupled to power an endergonic reaction with a G of 8.8 kcal/mol. The reaction is nonspontaneous. To take place, the reaction would need to couple to ATP hydrolysis. The reaction would result in products with a greater free-energy content than in the initial reactants. The reaction would proceed by itself but might be very slow. 9

10 True or false: The breakdown of food molecules in the gut does not require coupling of ATP hydrolysis, but enzymes are required to speed up these spontaneous reactions. true false, because enzymes change the G to a negative value false, because enzymes are not required, as breakdown is spontaneous and spontaneous reactions always occur very rapidly Answer: A 10

11 True or false: The breakdown of food molecules in the gut does not require coupling of ATP hydrolysis, but enzymes are required to speed up these spontaneous reactions. true false, because enzymes change the G to a negative value false, because enzymes are not required, as breakdown is spontaneous and spontaneous reactions always occur very rapidly 11

12 The oxidation of glucose to CO2 and H2O is highly exergonic: G  636 kcal/mole. This is spontaneous, but why is it very slow? Few glucose and oxygen molecules have the activation energy at room temperature. There is too much CO2 in the air. CO2 has higher energy than glucose. The formation of six CO2 molecules from one glucose molecule decreases entropy. The water molecules quench the reaction. Answer: A 12

13 The oxidation of glucose to CO2 and H2O is highly exergonic: G  636 kcal/mole. This is spontaneous, but why is it very slow? Few glucose and oxygen molecules have the activation energy at room temperature. There is too much CO2 in the air. CO2 has higher energy than glucose. The formation of six CO2 molecules from one glucose molecule decreases entropy. The water molecules quench the reaction. 13

14 Luciferase makes the G of the reaction more negative.
Firefly luciferase catalyzes the following reaction: luciferin  ATP  adenyl-luciferin  pyrophosphate Then the next reaction occurs spontaneously: adenyl-luciferin  O2  oxyluciferin  H2O  CO2  AMP  light What is the role of luciferase? Luciferase makes the G of the reaction more negative. Luciferase lowers the energy of the transition state of the reaction. Luciferase alters the equilibrium point of the reaction. Luciferase makes the reaction irreversible. Luciferase creates a phosphorylated intermediate. Answer: B Important question: enzymes do not affect the G of a reaction, just speed it up by lowering the energy of the transition state. 14

15 Luciferase makes the G of the reaction more negative.
Firefly luciferase catalyzes the following reaction: luciferin  ATP  adenyl-luciferin  pyrophosphate Then the next reaction occurs spontaneously: adenyl-luciferin  O2  oxyluciferin  H2O  CO2  AMP  light What is the role of luciferase? Luciferase makes the G of the reaction more negative. Luciferase lowers the energy of the transition state of the reaction. Luciferase alters the equilibrium point of the reaction. Luciferase makes the reaction irreversible. Luciferase creates a phosphorylated intermediate. 15

16 In the energy diagram below, which of the energy changes would be the same in both the enzyme-catalyzed and uncatalyzed reactions? a b c d e Answer: C 16

17 In the energy diagram below, which of the energy changes would be the same in both the enzyme-catalyzed and uncatalyzed reactions? a b c d e 17

18 If this is an enzyme-catalyzed reaction, how can the rate of this reaction be increased beyond the maximum velocity in this figure? Increase the substrate concentration. Increase the amount of enzyme. Raise the temperature to be more optimal. B is the best choice, but A and C are also possible. There is no way to increase the rate of the reaction any further. Answer: D 18

19 If this is an enzyme-catalyzed reaction, how can the rate of this reaction be increased beyond the maximum velocity in this figure? Increase the substrate concentration. Increase the amount of enzyme. Raise the temperature to be more optimal. B is the best choice, but A and C are also possible. There is no way to increase the rate of the reaction any further. 19

20 Vioxx and other prescription nonsteroidal anti-inflammatory drugs (NSAIDs) are potent inhibitors of the cyclooxygenase-2 (COX-2) enzyme. High substrate concentrations reduce the efficacy of inhibition by these drugs. These drugs are competitive inhibitors. noncompetitive inhibitors. allosteric regulators. prosthetic groups. feedback inhibitors. Answer: A Sources Chan et al. Rofecoxib [Vioxx, MK-0966; 4-(4'-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: A potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles, Pharmacology 290:551–560 (1999). Copeland et al. Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase, Proceedings of the National Academy of Sciences 91:11202–11206 (1994). 20

21 Vioxx and other prescription nonsteroidal anti-inflammatory drugs (NSAIDs) are potent inhibitors of the cyclooxygenase-2 (COX-2) enzyme. High substrate concentrations reduce the efficacy of inhibition by these drugs. These drugs are competitive inhibitors. noncompetitive inhibitors. allosteric regulators. prosthetic groups. feedback inhibitors. 21

22 How does the flow of energy through life differ from the flow of matter through life?
Matter can be recycled, while some energy is always converted to unusable forms like heat. Matter is brought into life from outside, while energy is generated from within life. Life is able to convert energy into matter, through photosynthesis. Matter is conserved, while life causes energy to be lost over time. Life uses the flow of matter to keep its energy state unbalanced. Answer: A

23 How does the flow of energy through life differ from the flow of matter through life?
Matter can be recycled, while some energy is always converted to unusable forms like heat. Matter is brought into life from outside, while energy is generated from within life. Life is able to convert energy into matter, through photosynthesis. Matter is conserved, while life causes energy to be lost over time. Life uses the flow of matter to keep its energy state unbalanced.

24 The form of energy that is typically LEAST useful to life is energy in
concentration gradients. electrical gradients. differences between distinct forms of molecules. the form of heat. electromagnetic radiation. Answer: D

25 The form of energy that is typically LEAST useful to life is energy in
concentration gradients. electrical gradients. differences between distinct forms of molecules. the form of heat. electromagnetic radiation.

26 Which choice best describes what the H ATPase (see figure on next slide) does in terms of flow of energy in many cells? It converts light energy into energy in a concentration gradient. It converts matter into energy in the form of an electrochemical gradient. It pumps protons up their pressure gradient. It converts chemical energy to energy in an electrochemical gradient and heat. It converts energy in a concentration gradient to energy in an electrical gradient. Answer: d (Image modified from fig )

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28 Which choice best describes what the H ATPase (see figure on next slide) does in terms of flow of energy in many cells? It converts light energy into energy in a concentration gradient. It converts matter into energy in the form of an electrochemical gradient. It pumps protons up their pressure gradient. It converts chemical energy to energy in an electrochemical gradient and heat. It converts energy in a concentration gradient to energy in an electrical gradient.

29 In the reaction shown on the next slide, which of the following statements is true?
The greater the activation energy barrier, the slower the reaction rate. The less energy released when products form, the slower the reaction rate. The more types of reactants involved in the reaction, the faster the reaction. The higher the net G of the reaction, the faster the reaction rate. The more bonds altered by the reaction, the faster the reaction rate. Answer: a (Image from fig )

30 The reactants AB and CD must absorb enough energy from the surroundings to reach the unstable transition state, where bonds can break. After bonds have broken, new bonds form, releasing energy to the surroundings.

31 In the reaction shown on the next slide, which of the following is true?
The greater the activation energy barrier, the slower the reaction rate. The less energy released when products form, the slower the reaction rate. The more types of reactants involved in the reaction, the faster the reaction. The higher the net G of the reaction, the faster the reaction rate. The more bonds altered by the reaction, the faster the reaction rate.

32 Some enzymes can couple the hydrolysis of ATP to ion transport by having
energy from ATP hydrolysis alter the free energy changes of another reaction. cofactors that act to transfer energy and matter from one reaction to another. phosphate groups from the ATP temporarily donated to the ions. the coupled processes both be exergonic. changes during ATP hydrolysis alter the enzyme’s shape, forcing ionic transport to occur. Answer: E (Image from fig. 8.15a)

33 Some enzymes can couple the hydrolysis of ATP to ion transport by having
energy from ATP hydrolysis alter the free energy changes of another reaction. cofactors that act to transfer energy and matter from one reaction to another. phosphate groups from the ATP temporarily donated to the ions. the coupled processes both be exergonic. changes during ATP hydrolysis alter the enzyme’s shape, forcing ionic transport to occur.

34 The combination of ATP with water, leading to the formation of ADP and free inorganic phosphate ion,
has a very large G compared to other reactions occurring in life. is an exergonic reaction due to the energy stored in the bonds of the water molecule. has neither the smallest nor the largest G seen in reactions in life. will occur rapidly even in the absence of a specific enzyme. has a very small G compared to other reactions occurring in life. Answer: C (Image from figure 8.9a)

35 The combination of ATP with water, leading to the formation of ADP and free inorganic phosphate ion,
has a very large G compared to other reactions occurring in life. is an exergonic reaction due to the energy stored in the bonds of the water molecule. has neither the smallest nor the largest G seen in reactions in life. will occur rapidly even in the absence of a specific enzyme. has a very small G compared to other reactions occurring in life.

36 The lower data set was done using a suboptimal pH for this enzyme.
In their work, Commerford et al. (2002) isolated the glucose-6-phosphatase enzyme from rat liver tissue. Enzyme reaction rates were assayed twice at various concentrations of the substrate (see figure on next slide). Which choice is LEAST likely to account for the differences between these two sets of data? The lower data set was done using a suboptimal pH for this enzyme. The upper data set was taken nearer to this enzyme’s temperature optimum. The upper curve’s assay was done using a higher enzyme concentration. The lower data set was taken while a competitive inhibitor was present. Answer: D

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38 In their work, Commerford et al
In their work, Commerford et al. (2002) isolated the glucose-6-phosphatase enzyme from rat liver tissue. Enzyme reaction rates were assayed twice at various concentrations of the substrate. Which choice is LEAST likely to account for the differences between these two sets of data? The lower data set was done using a suboptimal pH for this enzyme. The upper data set was taken nearer to this enzyme’s temperature optimum. The upper curve’s assay was done using a higher enzyme concentration. The lower data set was taken while a competitive inhibitor was present.

39 The relative free energies for progress through the reaction A + B ÷ C + D under standard conditions (1 M concentrations and standard temperature and pressure) are shown on the next slide. Changes in the conditions resulted in the altered plots shown below. Which choice matches the proper plot in the correct order for the reaction run with? An enzyme being present. At a higher temperature. With lower concentrations of A + B. At a colder temperature. 1 A, 2 D, 3 B, 4 C d) 1 B, 2 A, 3 D, 4 C 1 B, 2 C, 3 D, 4 A e) 1 D, 2 B, 3 C, 4 D 1 C, 2 D, 3 A, 4 B Answer: B

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41 The relative free energies for progress through the reaction A + B ÷ C + D under standard conditions (1 M concentrations and standard temperature and pressure) are shown on the next slide. Changes in the conditions resulted in the altered plots shown below. Which choice matches the proper plot in the correct order for the reaction run with? An enzyme being present. At a higher temperature. With lower concentrations of A + B. At a colder temperature. 1 A, 2 D, 3 B, 4 C d) 1 B, 2 A, 3 D, 4 C 1 B, 2 C, 3 D, 4 A e) 1 D, 2 B, 3 C, 4 D 1 C, 2 D, 3 A, 4 B

42 How are the effects of negative feedback and allosteric factors similar to how enzymes often couple reactions? All can drive an endergonic reaction forward by their exergonic energy changes. These all often involve inducing structural changes in the enzyme, influencing its activities. Permanent changes are made to the item(s) bound by the enzyme in each case. Each leads to the formation of new covalent bonds in the enzyme. All three can lower the activation energy barrier and speed the rate of a reaction. Answer: B

43 How are the effects of negative feedback and allosteric factors similar to how enzymes often couple reactions? All can drive an endergonic reaction forward by their exergonic energy changes. These all often involve inducing structural changes in the enzyme, influencing its activities. Permanent changes are made to the item(s) bound by the enzyme in each case. Each leads to the formation of new covalent bonds in the enzyme. All three can lower the activation energy barrier and speed the rate of a reaction.

44 A change in the coding region of a gene can lead to a new allele for that gene. Which property of the protein, coded for by this new allele, could be changed as a result? its affinity for its substrate the amino acid sequence in it its ability to be affected by allosteric factors the pH that is optimal for its activity All of the above could be altered by mutations. Answer: E

45 A change in the coding region of a gene can lead to a new allele for that gene. Which property of the protein, coded for by this new allele, could be changed as a result? its affinity for its substrate the amino acid sequence in it its ability to be affected by allosteric factors the pH that is optimal for its activity All of the above could be altered by mutations.


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