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Chapter 15 Principles of Metabolic Regulation
Multiple Choice Questions
1. Which of the following does not contribute to the regulation of enzymatic activity?
A) Protein phosphorylation
B) Allosteric regulation
C) Protein stability
D) mRNA stability
E) DNA stability
Regulation of metabolic pathways
2. For an enzyme to effectively change its activity in response to a change in substrate
concentration, it is most favorable for:
A) Km to be less than cellular substrate concentrations.
B) Km to be equal to cellular substrate concentrations.
C) Km to be greater than cellular substrate concentrations.
D) Vmax to be at the diffusion limit.
E) The substrate to also be an allosteric effector.
Regulation of metabolic pathways
3. Reaction steps that are far from equilibrium are good control points in metabolic pathways
because
A) the net flux through those steps is easily reversed.
B) the rate differences between the forward and reverse steps are often small.
C) these reactions occur most frequently in the cell.
D) these reactions are highly endergonic.
E) these reactions are highly exergonic.
Regulation of metabolic pathways
4. Aside from maintaining the integrity of its hereditary material, the most important general
metabolic concern of a cell is:
A) keeping its glucose levels high.
B) maintaining a constant supply and concentration of ATP.
C) preserving its ability to carry out oxidative phosphorylation.
D) protecting its enzymes from rapid degradation.
E) running all its major metabolic pathways at maximum efficiency.
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Regulation of metabolic pathways
5. The most sensitive indicator of the energetic status of the cell is the concentration of
A) AMP.
B) ADP.
C) ATP.
D) cAMP.
E) glucose.
Regulation of metabolic pathways
6. If the mass action ratio, Q, for a reaction under cellular conditions is larger than the equilibrium
constant, Keq, then:
A) the reaction will be at equilibrium.
B) the reaction will go backward and be endergonic.
C) the reaction will go backward and be exergonic.
D) the reaction will go forward and be endergonic.
E) the reaction will go forward and be exergonic.
Regulation of metabolic pathways
7. Which one of the following types of mechanisms is not known to play a role in the reversible
alteration of enzyme activity?
A) Activation by cleavage of an inactive zymogen
B) Allosteric response to a regulatory molecule
C) Alteration of the synthesis or degradation rate of an enzyme
D) Covalent modification of the enzyme
E) Interactions between catalytic and regulatory subunits
Regulation of metabolic pathways
8. The flux control coefficient for an enzyme in a multistep pathway depends on:
A) the concentration of the enzyme itself.
B) the concentration of other enzymes in the pathway.
C) the levels of regulatory molecules.
D) the amounts of substrate molecules present at each step.
E) All of the above
Analysis of metabolic control
9. The elasticity coefficient for an enzyme in a multistep pathway depends on:
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178
A) the concentration of the enzyme itself.
B) the levels of regulatory molecules.
C) the amounts of substrate molecules present at each step.
D) both A and C.
E) both B and C.
Analysis of metabolic control
10. Which of the following is an example of flux regulation, not flux control upon an increase in
blood glucose levels?
A) Induction of insulin
B) Increased glucose transport into cells
C) Induction of the synthesis of hexokinase
D) Induction of the synthesis of phosphofructokinase-1
E) Activation of glycogen synthase
Analysis of metabolic control
11. Gluconeogenesis must use “bypass reactions” to circumvent three reactions in the
glycolytic pathway that are highly exergonic and essentially irreversible. Reactions
carried out by which three of the enzymes listed must be bypassed in the gluconeogenic
pathway?
1) Hexokinase
2) Phosphoglycerate kinase
3) Phosphofructokinase-1
4) Pyruvate kinase
5) Triosephosphate isomerase
A) 1, 2, 3
B) 1, 2, 4
C) 1, 4, 5
D) 1, 3, 4
E) 2, 3, 4
Coordinated regulation of glycolysis and gluconeogenesis
12. There is reciprocal regulation of glycolytic and gluconeogenic reactions interconverting fructose-
6-phosphate and fructose-1,6-bisphosphate. Which one of the following statements about this
regulation is not correct?
A) Fructose-2,6-bisphosphate activates phosphofructokinase-1.
B) Fructose-2,6-bisphosphate inhibits fructose-1,6-bisphosphatase.
C) The fructose-1,6-bisphosphatase reaction is exergonic.
D) The phosphofructokinase-1 reaction is endergonic.
E) This regulation allows control of the direction of net metabolite flow through the pathway.
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179
Coordinated regulation of glycolysis and gluconeogenesis
13. An increase in which of these compounds leads to the dephosphorylation and activation
of phosphofructokinase–2?
A) Glucagon
B) Xyulose-5-phosphate
C) Pyruvate
D) Citrate
E) ADP
Coordinated regulation of glycolysis and gluconeogenesis
14. Cellular isozymes of pyruvate kinase are allosterically inhibited by:
A) high concentrations of AMP.
B) high concentrations of ATP.
C) high concentrations of citrate.
D) low concentrations of acetyl-CoA.
E) low concentrations of ATP.
Coordinated regulation of glycolysis and gluconeogenesis
15. Which of the following statements about gluconeogenesis in animal cells is true?
A) A rise in the cellular level of fructose-2,6-bisphosphate stimulates the rate of
gluconeogenesis.
B) An animal fed a large excess of fat in the diet will convert any fat not needed for energy
production into glycogen to be stored for later use.
C) The conversion of fructose 1,6-bisphosphate to fructose 6-phosphate is not catalyzed by
phosphofructokinase-1, the enzyme involved in glycolysis.
D) The conversion of glucose 6-phosphate to glucose is catalyzed by hexokinase, the same
enzyme involved in glycolysis.
E) The conversion of phosphoenol pyruvate to 2-phosphoglycerate occurs in two steps,
including a carboxylation.
Coordinated regulation of glycolysis and gluconeogenesis
16. Which of the following is not involved in up-regulating the transcription of glycolytic or
gluconeogenic enzymes?
A) Phosphofructokinase-2
B) Carbohydrate response element binding protein
C) Sterol response element binding protein
D) cAMP response element binding protein
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180
E) FOXO1
Coordinated regulation of glycolysis and gluconeogenesis
17. The enzyme glycogen phosphorylase:
A) catalyzes a cleavage of
(1 → 4) bonds.
B) catalyzes a hydrolytic cleavage of
(1 → 4) bonds.
C) is a substrate for a kinase.
D) uses glucose 6-phosphate as a substrate.
E) uses glucose as a substrate.
The metabolism of glycogen in animals
18. Glycogen is converted to monosaccharide units by:
A) glucokinase.
B) glucose-6-phosphatase
C) glycogen phosphorylase.
D) glycogen synthase.
E) glycogenase.
The metabolism of glycogen in animals
19. Which one of the following statements about mammalian glycogen synthase is not correct?
A) It is especially predominant in liver and muscle.
B) The donor molecule is a sugar nucleotide.
C) The phosphorylated form of this enzyme is inactive.
D) This enzyme adds glucose units to the nonreducing end of glycogen branches.
E) This enzyme adds the initial glucose unit to a tyrosine residue in glycogenin.
The metabolism of glycogen in animals
20. The glycogen-branching enzyme catalyzes:
A) degradation of (
1 → 4) linkages in glycogen
B) formation of (
1 → 4) linkages in glycogen.
C) formation of (
1 → 6) linkages during glycogen synthesis.
D) glycogen degradation in tree branches.
E) removal of unneeded glucose residues at the ends of branches.
The metabolism of glycogen in animals
21. Glycogenin:
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181
A) catalyzes the conversion of starch into glycogen.
B) is the enzyme responsible for forming branches in glycogen.
C) is the gene that encodes glycogen synthase.
D) is the primer on which new glycogen chains are initiated.
E) regulates the synthesis of glycogen.
The metabolism of glycogen in animals
22. Which of the following is true of glycogen synthase?
A) Activation of the enzyme involves a phosphorylation.
B) It catalyzes addition of glucose residues to the nonreducing end of a glycogen chain by
formation of (
1 → 4) bonds.
C) It uses glucose-6-phosphate as donor of glucose units
D) It catalyzes addition of glucose residues at branch points by formation of (
1 → 6) bonds.
E) The enzyme has measurable activity only in liver.
The metabolism of glycogen in animals
23. Which of the following statements is true of muscle glycogen phosphorylase?
A) It catalyzes phosphorolysis of the (
1 → 6) bonds at the branch points of glycogen.
B) It catalyzes the degradation of glycogen by hydrolysis of glycosidic bonds.
C) It degrades glycogen to form glucose 6-phosphate.
D) It exists in an active (a) form and an inactive (b) form that is allosterically regulated by
AMP.
E) It removes glucose residues from the reducing ends of the glycogen chains.
Coordinated regulation of glycogen synthesis and breakdown
24. Which of the following is true of glycogen synthesis and breakdown?
A) Phosphorylation activates the enzyme responsible for breakdown, and inactivates the
synthetic enzyme.
B) Synthesis is catalyzed by the same enzyme that catalyzes breakdown.
C) The glycogen molecule “grows” at its reducing end.
D) The immediate product of glycogen breakdown is free glucose.
E) Under normal circumstances, glycogen synthesis and glycogen breakdown occur
simultaneously and at high rates.
Coordinated regulation of glycogen synthesis and breakdown
25. Glycogen phosphorylase a can be inhibited at an allosteric site by:
A) AMP.
B) calcium.
Chapter 15 Principles of Metabolic Regulation
182
C) GDP.
D) glucagon.
E) glucose.
Coordinated regulation of glycogen synthesis and breakdown
26. Which one of the following directly results in the activation of glycogen synthase?
A) Binding of glucose-6-phosphate
B) Dephosphorylation of multiple residues by phosphoprotein phosphorylase-1 (PP1)
C) Phosphorylation of specific residues by casein kinase II (CKII)
D) Phosphorylation of specific residues by glycogen synthase kinase-3 (GSK-3)
E) The presence of insulin
Coordinated regulation of glycogen synthesis and breakdown
27. Which one of the following is not a characteristic of phosphoprotein phosphorylase-1
(PP1)?
A) PP1 can be phosphorylated by protein kinase A (PKA).
B) PP1 can dephosphorylate glycogen phosphorylase, glycogen synthase, and phosphorylase
kinase.
C) PP1 is allosterically activated by glucose-6-phosphate.
D) PP1 is inhibited by activated glycogen phosphorylase
E) PP1 is phosphorylated by glycogen synthase kinase-3 (GSK3).
Coordinated regulation of glycogen synthesis and breakdown
Short Answer Questions
28. Why is it important for proper cell function that proteins turn over rather than persisting
indefinitely after being synthesized?
29. Explain the difference between homeostasis and equilibrium.
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183
30. What are the regulatory implications for the cell with regard to ATP and AMP, given that the
former are generally high, and the latter are low?
31. Explain why reactions that are far from equilibrium need to be regulated.
32. Briefly explain the differences between the flux control, elasticity, and response coefficients.
33. Explain the distinction between metabolic “regulation” and metabolic “control” in a multienzyme
pathway.
34. In the glycolytic path from glucose to pyruvate, three steps are practically irreversible. What are
these steps, and how is each bypassed in gluconeogenesis? What advantages does an organism
gain from having separate pathways for anabolic and catabolic metabolism? What are the
disadvantages?
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184
35. What is a “futile cycle”? Give an example of a potential futile cycle in carbohydrate metabolism,
and describe methods used by cells or organisms to avoid the operation of the futile cycle.
36. Why is citrate, in addition to being a metabolic intermediate in aerobic oxidation of fuels, an
important control molecule for a variety of enzymes?
37. Under what circumstances does the bifunctional protein phosphofructokinase-2/fructose 2,6-
bisphosphatase (PFK-2/FBPase-2) become phosphorylated, and what are the consequences of its
phosphorylation to the glycolytic and gluconeogenic pathways?
Chapter 15 Principles of Metabolic Regulation
185
38. Briefly outline the pathway by which glucose activates the synthesis of pyruvate kinase.
39. Name three glycolytic enzymes whose expression is are up-regulated in response to insulin and
two gluconeogenic enzymes whose expression is down-regulated in response to insulin.
40. Describe the process of glycogen breakdown in muscle. Include a description of the structure of
glycogen, the nature of the breakdown reaction and the breakdown product, and the required
enzyme(s).
41. Glycogen synthesis and glycogen breakdown are catalyzed by separate enzymes. Contrast the
reactions in terms of substrate, cofactors (if any), and regulation.
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42. In mammalian liver, glucose-1-phosphate, the product of glycogen phosphorylase, can enter
glycolysis or replenish blood glucose. Describe the reactions by which these two processes are
carried out.
43. Diagram the pathway from glucose to glycogen; show the participation of cofactors and name the
enzymes involved.
44. Show the reaction catalyzed by glycogen synthase.
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45. What is the biological advantage of synthesizing glycogen with many branches?
46. Explain the role of glycogenin.
47. Order the steps leading to glycogen breakdown resulting from the stimulation of liver
cells by glucagon.
1) Activation of protein kinase A (PKA)
2) cAMP levels rise
3) Phosphorylation of phosphorylase b
4) Phosphorylation of phosphorylase b kinase
5) Stimulation of adenyl cyclase
48. Order the steps leading to glycogen synthesis resulting from the stimulation of liver cells by
glucose.
1) Xyulose-5-phosphate is formed
2) Glucose is phosphorylated to glucose-6-phosphate
3) Glycogen synthase is dephosphorylated
4) Protein phosphatase 2A is activated
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49. Many of the steps in the pathways described in this chapter are essentially irreversible (for A →
B G << 0). As a result, if the cell wants to carry out the reverse transformation, it must use a
different pathway to go from B → A. For each of the enzymes on the left, pick the enzyme on
the right that carries out the reverse transformation (not necessarily the reverse reaction).
a) hexokinase 1) glycogen phosphorylase
b) fructose 1,6-bisphosphatase 2) pyruvate carboxylase & PEP carboxylase
c) glycogen synthase 3) phosphofructokinase I
d) pyruvate kinase 4) glucose-6-phosphatase
