1.  Complex patterns. What is meant by intermediary metabolism?

2.  Opposites. Differentiate between anabolism and catabolism.

3.  Graffiti. While walking to biochemistry class with a friend, you see the following graffiti spray painted on the wall of the science building: “When a system is in equilibrium, the Gibbs free energy is maximum.” You are disgusted, not only at the vandalism, but at the ignorance of the vandal. Your friend asks you to explain. How do you respond?

4.  Why bother to eat? What are the three primary uses for cellular energy?

5.  Like Antony and Cleopatra. Match the terms in the two columns.

6.  Energy to burn. What factors account for the high phosphoryl-transfer potential of nucleoside triphosphates? ✓ 3

7.  Currency matters. Why does it make good sense to have a single nucleotide, ATP, function as the cellular energy currency? ✓ 3

8.  Close, personal friends. Why is ATP usually associated with magnesium or manganese ions? ✓ 3

9.  Environmental conditions. The standard free energy of hydrolysis for ATP is −30.5 kJ mol⁻¹ (−7.3 kcal mol⁻¹):

What conditions might be changed to alter the free energy of hydrolysis? ✓ 3

10.  Energy flow. What is the direction of each of the following reactions when the reactants are initially present in equimolar amounts? Use the data given in Table 15.1. ✓ 4

(a) ATP + H₂O ⇌ ADP + P_i

(b) ATP + glycerol ⇌ glycerol 3−phosphate + ADP

(c) ATP + pyruvate ⇌ phosphoenolpyruvate + ADP

(d) ATP + glucose ⇌ glucose 6−phosphate + ADP

11.  A proper inference. What information do the ΔG°′ data given in Table 15.1 provide about the relative rates of hydrolysis of pyrophosphate and acetyl phosphate?

12.  A potent donor. Consider the following reaction. ✓ 4



(a) Calculate ΔG°′ and K′_eq at 25°C for this reaction by using the data given in Table 15.1.

(b) What is the equilibrium ratio of pyruvate to phosphoenolpyruvate if the ratio of ATP to ADP is 10?

13.  Isomeric equilibrium. Calculate ΔG°′ for the isomerization of glucose 6-phosphate to glucose 1-phosphate. What is the equilibrium ratio of glucose 6-phosphate to glucose 1-phosphate at 25°C?

14.  Activated acetate. The formation of acetyl CoA from acetate is an ATP-driven reaction:



(a) Calculate ΔG°′ for this reaction by using data given in this chapter.

(b) The PP_i formed in the preceding reaction is rapidly hydrolyzed in vivo because of the ubiquity of inorganic pyrophosphatase. The ΔG°′ for the hydrolysis of PP_i is −19.2 kJ mol⁻¹ (−4.6 kcal mol⁻¹). Calculate the ΔG°′ for the overall reaction, including pyrophosphate hydrolysis. What effect does the hydrolysis of PP_i have on the formation of acetyl CoA?

15.  Brute force? Metabolic pathways frequently contain reactions with positive standard free-energy values, yet the reactions still take place. How is it possible? ✓ 4

16.  Recurring motif. What is the structural feature common to ATP, FAD, NAD⁺, and CoA? ✓ 5

17.  Outsourcing. Outsourcing, a common business practice, is contracting with another business to perform a particular function. Higher organisms were the original outsourcers, frequently depending on lower organisms to perform key biochemical functions. Give an example from this chapter of biochemical outsourcing.

18.  High-energy electrons. What are the activated electron carriers for catabolism? For anabolism?

19.  Less reverberation. Thioesters, common in biochemistry, are more unstable (energy rich) than oxygen esters. Explain.

20.  Staying in control. What are the three principal means of controlling metabolic reactions?

21.  Running downhill. Glycolysis is a series of 10 linked reactions that convert one molecule of glucose into two molecules of pyruvate with the concomitant synthesis of two molecules of ATP (Chapter 16). The ΔG°′ for this set of reactions is −35.6 kJ mol⁻¹ (−8.5 kcal mol⁻¹), whereas the ΔG° is −90 kJ mol⁻¹ (−22 kcal mol⁻¹). Explain why the free-energy release is so much greater under intracellular conditions than under standard conditions.

22.  Oxidation matters. Examine the pairs of molecules, and identify the more reduced molecule in each pair. ✓ 5

23.  Breakdown products. Digestion is the first stage in the extraction of energy from food, but no useful energy is acquired in this stage. Why is digestion considered a stage in energy extraction?

24.  Kinetic versus thermodynamic. The reaction of NADH with oxygen to produce NAD⁺ and H₂O is very exergonic, yet the reaction of NADH and oxygen takes place very slowly. Why does a thermodynamically favorable reaction not take place rapidly?

25.  Acid strength. The pK_a of an acid is a measure of its proton-group-transfer potential.

(a) Derive a relation between ΔG°′ and pK_a.

(b) What is the ΔG°′ for the ionization of acetic acid, which has a pK_a of 4.8?

26.  Activated sulfate. Fibrinogen, a precursor to the blood-clot protein fibrin, contains tyrosine-O-sulfate. Propose an activated form of sulfate that could react in vivo with the aromatic hydroxyl group of a tyrosine residue in a protein to form tyrosine-O-sulfate.

27.  Opposites attract. The graph below shows how the ΔG for the hydrolysis of ATP varies as a function of the Mg²⁺ concentration (pMg = −log[Mg²⁺]). ✓ 3



(a) How does decreasing [Mg²⁺] affect the ΔG of hydrolysis for ATP?

(b) Explain this effect.

28.  Raison d’être. The muscles of some invertebrates are rich in arginine phosphate (phosphoarginine). Propose a function for this amino acid derivative.

29.  Ergogenic help or hindrance? Creatine is a popular, but untested, dietary supplement.

(a) What is the biochemical rationale for the use of creatine?

(b) What type of exercise would most benefit from creatine supplementation?

30.  Standard conditions versus real life 1. The enzyme aldolase catalyzes the following reaction in the glycolytic pathway:



The ΔG°′ for the reaction is +23.8 kJ mol⁻¹ (+5.7 kcal mol⁻¹), whereas the ΔG° in the cell is −1.3 kJ mol⁻¹ (−0.3 kcal mol⁻¹). Calculate the ratio of reactants to products under equilibrium and intracellular conditions. Using your results, explain how the reaction can be endergonic under standard conditions and exergonic under intracellular conditions.

31.  Standard conditions versus real life 2. In "ATP Hydrolysis Drives Metabolism by Shifting the Equilibrium of Coupled Reactions" (Section 15.3), a reaction, A ⇌ B, with a ΔG°′ = +16.7 kJ mol⁻¹ (+4.0 kcal mol⁻¹) is shown to have a K_eq of 1.15 × 10⁻³. The K_eq is increased to 2.67 × 10² if the reaction is coupled to ATP hydrolysis under standard conditions. The ATP-generating system of cells maintains the [ATP]/[ADP][P_i] ratio at a high level, typically of the order of 500 M⁻¹. Calculate the ratio of B/A under cellular conditions. ✓ 4