1.  It is not hard to meet expenses. They are everywhere. What energetic barrier prevents glycolysis from simply running in reverse to synthesize glucose? What is the energetic cost of overcoming this barrier? ✓ 3

2.  Like Minneapolis and St. Paul. Match each term with its description.

3.  Road blocks. What reactions of glycolysis are not reversible under intracellular conditions? How are these reactions bypassed in gluconeogenesis? ✓ 3

4.  Biotin snatcher. Avidin, a 70-kDa protein in egg white, has very high affinity for biotin. In fact, it is a highly specific inhibitor of biotin enzymes. Which of the following conversions would be blocked by the addition of avidin to a cell homogenate?

(a) Glucose → pyruvate

(b) Pyruvate → glucose

(c) Oxaloacetate → glucose

(d) Malate → oxaloacetate

(e) Pyruvate → oxaloacetate

(f) Glyceraldehyde 3-phosphate → fructose 1,6-bisphosphate

5.  Working at cross-purposes? Gluconeogenesis takes place during intense exercise, which seems counterintuitive. Why would an organism synthesize glucose and, at the same time, use glucose to generate energy? ✓ 3

6.  Different needs. Liver is primarily a gluconeogenic tissue, whereas muscle is primarily glycolytic. Why does this division of labor make good physiological sense? ✓ 3

7.  Metabolic mutants. What would be the effect on an organism’s ability to use glucose as an energy source if a mutation inactivated glucose 6-phosphatase in the liver?

8.  Never let me go. Why does the lack of glucose 6-phosphatase activity in the brain and muscle make good physiological sense?

9.  Which way to go? Compare the roles of lactate dehydrogenase in gluconeogenesis and in lactic acid fermentation. ✓ 3

10.  Match ’em 1. The following sequence is a part of the sequence of reactions in gluconeogenesis:



Match the items on the left with the capital letters representing the reaction in the gluconeogenic pathway.

11.  Salvaging resources. In starvation, protein degradation takes place in muscle. Explain how this degradation might affect gluconeogenesis in the liver.

12.  Counting high-energy compounds 1. How many NTP molecules are required for the synthesis of one molecule of glucose from two molecules of pyruvate? How many NADH molecules? ✓ 3

13.  Counting high-energy compounds 2. How many NTP molecules are required to synthesize glucose from each of the following compounds? ✓ 3

(a) Glucose 6-phosphate

(b) Fructose 1,6-bisphosphate

(c) Two molecules of oxaloacetate

(d) Two molecules of dihydroxyacetone phosphate

14.  Two cycles. What are the two potential substrate cycles in the glycolytic and gluconeogenic pathways? ✓ 4

15.  Useful cycles. What is the regulatory role for the substrate cycles in glycolysis and gluconeogenesis? ✓ 4

16.  Not running at cross-purposes. Describe the reciprocal regulation of gluconeogenesis and glycolysis. ✓ 4

17.  Match ’em 2. Indicate which of the conditions listed in the right-hand column increase the activity of the glycolytic and gluconeogenic pathways. ✓ 4

18.  Lending a hand. How might enzymes that remove amino groups from alanine and aspartate contribute to gluconeogenesis?

19.  Even more metabolic mutants. Predict the effect of each of the following mutations on the pace of glycolysis in liver cells. ✓ 4

(a) Loss of the allosteric site for ATP in phosphofructokinase

(b) Loss of the binding site for citrate in phosphofructokinase

(c) Loss of the phosphatase domain of the bifunctional enzyme that controls the level of fructose 2,6-bisphosphate

(d) Loss of the binding site for fructose 1,6-bisphosphate in pyruvate kinase

20.  A salvage operation. Glycerol is released when lipids are used as a fuel. The released glycerol can be salvaged and can be used in glycolysis or gluconeogenesis in the liver. Show the reactions that are required for this conversion.

21.  Hungry yeast. Yeast are facultative anaerobes—they can grow in the absence of oxygen (anaerobically) using alcoholic fermentation or in the presence of oxygen (aerobically) using cellular respiration. Interestingly, yeast cannot live anaerobically using glycerol as their only fuel source. Explain why yeast cannot survive metabolizing glycerol anaerobically.

22.  Cool bees. In principle, a futile cycle that includes phosphofructokinase and fructose 2,6-bisphosphatase could be used to generate heat. The heat could be used to warm tissues. For instance, certain bumblebees have been reported to use such a futile cycle to warm their flight muscles on cool mornings.

Scientists undertook a series of experiments to determine if a number of species of bumblebee use this futile cycle. Their approach was to measure the activity of PFK and F-1,6-BPase in flight muscle. ✓ 3

(a) What was the rationale for comparing the activities of these two enzymes?

(b) The following data show the activities of both enzymes for a variety of bumblebee species (genera Bombus and Psithyrus). Do these results support the notion that bumblebees use futile cycles to generate heat? Explain.



(c) In which species might futile cycling take place? Explain your reasoning.

(d) Do these results prove that futile cycling does not participate in heat generation?

23.  Waste not, want not. Why is the conversion of lactic acid from the blood into glucose in the liver in an organism’s best interest?

24.  More metabolic mutants. What are the likely consequences of a genetic disorder rendering fructose 1,6-bisphosphatase in the liver less sensitive to regulation by fructose 2,6-bisphosphate? ✓ 4

25.  Tracing carbon atoms. If cells synthesizing glucose from lactate are exposed to CO₂ labeled with ¹⁴C, what will be the distribution of label in the newly synthesized glucose?

26.  Powering pathways. Compare the stoichiometries of glycolysis and gluconeogenesis. Recall that the input of one ATP equivalent changes the equilibrium constant of a reaction by a factor of about 10⁸. By what factor do the additional high-phosphoryl-transfer compounds alter the equilibrium constant of gluconeogenesis? ✓ 3