1.  Just right. Suggest some possible reasons why glucose is fuel used by all organisms.

2.  Like the owl and the pussycat. Match each term with its description.

3.  Who takes? Who gives? Lactic acid fermentation and alcoholic fermentation are oxidation–reduction reactions. Identify the ultimate electron donor and electron acceptor.

4.  ATP yield. Each of the following molecules is processed by glycolysis to lactate. How much ATP is generated from each molecule?

(a) Glucose 6-phosphate

(b) Dihydroxyacetone phosphate

(c) Glyceraldehyde 3-phosphate

(d) Fructose

(e) Sucrose

5.  Enzyme redundancy? Why is it advantageous for the liver to have both hexokinase and glucokinase to phosphorylate glucose?

6.  Enzyme properties. In the liver and the pancreas, hexokinase and glucokinase phosphorylate glucose. Glucokinase is active only when the blood concentration of glucose is high. How might glucokinase differ kinetically from hexokinase so as to function only at high glucose levels?

7.  Required isomerization. Why is the isomerization of glucose 6-phosphate to fructose 6-phosphate an important step in glycolysis? How is the conversion of the fructose isomer back into the glucose isomer prevented?

8.  Magic? The interconverison of DHAP and GAP greatly favors the formation of DHAP at equilibrium. Yet the conversion of DHAP by triose phosphate isomerase proceeds readily. Why? ✓ 1

9.  Between two extremes. What is the role of a thioester in the formation of ATP in glycolysis?

10.  Corporate sponsors. Some of the early research on glycolysis was supported by the brewing industry. Why would the brewing industry be interested in glycolysis? ✓ 2

11.  Recommended daily allowance. The recommended daily allowance for the vitamin niacin is 15 mg per day. How would glycolysis be affected by niacin deficiency? ✓ 2

12.  Who’s on first? Although both hexokinase and phosphofructokinase catalyze irreversible steps in glycolysis and the hexokinase-catalyzed step is first, phosphofructokinase is nonetheless the pacemaker of glycolysis. What does this information tell you about the fate of the glucose 6-phosphate formed by hexokinase?

13.  The tortoise and the hare. Why is the regulation of phosphofructokinase by energy charge not as important in the liver as it is in muscle? ✓ 1

14.  Running in reverse. Why can’t the reactions of the glycolytic pathway simply be run in reverse to synthesize glucose?

15.  Destiny. What are the principle fates of pyruvate generated in glycolysis?

16.  Road blocks. What reactions of glycolysis are irreversible under intracellular conditions?

17.  No pickling. Why is it in the muscle’s best interest to export lactic acid into the blood during intense exercise?

18.  Proper preparation. Describe the pathways by which fructose is prepared for entry into glycolysis.

19.  Trouble ahead. Suppose that an obligate anaerobe suffered a mutation that resulted in the loss of triose phosphate isomerase activity. How would this loss affect the ATP yield of fermentation? Could such an organism survive?

20.  High potential. What is the equilibrium ratio of phosphoenolpyruvate to pyruvate under standard conditions when [ATP]/[ADP] = 10?

21.  Hexose-triose equilibrium. What are the equilibrium concentrations of fructose 1,6-bisphosphate, dihydroxyacetone phosphate, and glyceraldehyde 3-phosphate when 1 mM fructose 1,6-bisphosphate is incubated with aldolase under standard conditions?

22.  Distinctive sugars. The intravenous infusion of fructose into healthy volunteers leads to a two- to fivefold increase in the level of lactate in the blood, a far greater increase than that observed after the infusion of the same amount of glucose.

(a) Why is glycolysis more rapid after the infusion of fructose?

(b) Fructose has been used in place of glucose for intravenous feeding. Why is this use of fructose unwise?

23.  Arsenate poisoning. Arsenate (AsO₄³⁻) closely resembles P_i in structure and reactivity. In the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase, arsenate can replace phosphate in attacking the energy-rich thioester intermediate. The product of this reaction, 1-arseno-3-phosphoglycerate, is unstable. It and other acyl arsenates are rapidly and spontaneously hydrolyzed. What is the effect of arsenate on energy generation in a cell?

24.  Reduce, reuse, recycle. In the conversion of glucose into two molecules of lactate, the NADH generated earlier in the pathway is oxidized to NAD⁺. Why is it not to the cell’s advantage to simply make more NAD⁺ so that the regeneration would not be necessary? After all, the cell would save much energy because it would no longer need to synthesize lactic acid dehydrogenase. ✓ 2

25.  Diverted resources. Phosphofructokinase converts fructose 6-phosphate to fructose 1,6-bisphosphate, the committed step on the pathway that synthesizes ATP. However, some fructose 6-phosphate is converted into fructose 2,6-bisphosphate. Explain why depleting the substrate of PFK to form fructose 2,6-bisphosphate is not a wasteful use of substrate.

26.  Like Batman and Robin. Match parts a through j with parts 1 through 10.

27.  State function. Fructose 2,6-bisphosphate is a potent stimulator of phosphofructokinase. Explain how fructose 2,6-bisphosphate might function in the concerted model for allosteric enzymes.

28.  Not just for energy. People with galactosemia display central nervous system abnormalities even if galactose is eliminated from the diet. The precise reason for this is not known. Suggest a plausible explanation.

29.  Not MTV. A ligand-gated ion channel and a voltage-gated ion channel play keys roles in the secretion of insulin by the pancreas. What are the channels, and what is their function in insulin secretion? ✓ 2

30.  Power to the rbc! Hexokinase in red blood cells has a K_M of approximately 50 μM. Because life is hard enough as it is, let’s assume that the hexokinase displays Michaelis–Menten kinetics. What concentration of blood glucose would yield v_o equal to 90% V_max? What does this result tell you if normal blood-glucose levels range between approximately 3.6 and 6.1 mM?

31.  Now that’s unusual. Phosphofructokinase has been isolated from the hyperthermophilic archaeon Pyrococcus furiosus. The kinase was subjected to standard biochemical analysis to determine basic catalytic parameters. The processes under study were of the form



The assay measured the increase in fructose 1,6-bisphosphate. Selected results are shown in the adjoining graph.



(a) How does the P. furiosus phosphofructokinase differ from the phosphofructokinase considered in this chapter?

(b) What effects do AMP and ATP have on the reaction with ADP?

32.  Confused? The adjoining graph shows muscle phosphofructokinase activity as a function of ATP concentration in the presence of a constant concentration of fructose 6-phosphate. Explain these results, and discuss how they relate to the role of phosphofructokinase in glycolysis. ✓ 1

33.  Brewing. The adjoining graph shows results of experiments on the alcoholic fermentation of glucose with the use of yeast extracts. The graph shows the volume of carbon dioxide released (y axis) as a function of time (x axis). ✓ 2



(a) Is measuring the rate of carbon dioxide release a reliable means to measure alcoholic fermentation? Explain.

(b) Why is glucose fermentation dependent on phosphate?

(c) Why is more carbon dioxide generated if the extract is supplemented with phosphate?

(d) During the fermentation, what would the ratio of carbon dioxide generated to phosphate consumed be expected to be?

(e) When fermentation slowed, a hexose bisphosphate accumulated. What is this compound, and why would it accumulate?

34.  Kitchen chemistry. Sucrose is commonly used to preserve fruits. Why is glucose not suitable for preserving foods? ✓ 1

35.  Tracing carbon atoms. Glucose labeled with ¹⁴C at C-1 is incubated with the glycolytic enzymes and necessary cofactors.

(a) What is the location of ¹⁴C in the pyruvate that is formed? (Assume that the interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate is very rapid compared with the subsequent step.)

(b) If the specific activity of the glucose substrate is 10 mCi mmol⁻¹, what is the specific activity of the pyruvate that is formed?

36.  Lactic acid fermentation. ✓ 2

(a) Write a balanced equation for the conversion of glucose into lactate.

(b) Calculate the standard free-energy change of the formation of lactate from glucose by using the data given in Table 16.1 and the fact that ΔG°′ is −25 kJ mol⁻¹ (−6 kcal mol⁻¹) for the following reaction:



(c) What is the free-energy change (ΔG, not ΔG°′) of this reaction when the concentrations of reactants are glucose, 5 mM; lactate, 0.05 mM; ATP, 2 mM; ADP, 0.2 mM; and P_i, 1 mM?

37.  Après vous. Why is it physiologically advantageous for the pancreas to use GLUT2, with a high K_M value, as the transporter that allows glucose entry into ß cells?

38.  Bypass. In the liver, fructose can be converted into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate without passing through the phosphofructokinase-regulated reaction. Show the reactions that make this conversion possible. Why might ingesting high levels of fructose have deleterious physiological effects? ✓ 1

39.  An informative analog. Xylose has the same structure as that of glucose except that xylose has a hydrogen atom at C-5 in place of a hydroxymethyl group. The rate of ATP hydrolysis by hexokinase is markedly enhanced by the addition of xylose. Why? ✓ 1

40.  Quick-change artist. Adenylate kinase is responsible for interconverting the adenylate nucleotide pool:



The equilibrium constant for this reaction is close to 1, inasmuch as the number of phosphoanhydride bonds is the same on each side of the equation. Use the equation for the equilibrium constant for this reaction to show why changes in [AMP] are a more effective indicator of the adenylate pool than those in [ATP]. ✓ 1