Deck 15: Principles of Metabolic Regulation

Question 1

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.

Answer 1

AMP.

Question 2

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.

Answer 2

The phosphofructokinase-1 reaction is endergonic.

Question 3

If the mass action ratio,Q,for a reaction under cellular conditions is larger than the equilibrium constant,K_eq,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.

Answer 3

the reaction will go backward and be exergonic.

Question 4

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

Question 5

The elasticity coefficient for an enzyme in a multistep pathway depends on:

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.

Question 6

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

Question 7

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

Question 8

The glycogen-branching enzyme catalyzes:

A)degradation of ( $\alpha$ 1 $\rightarrow$ 4)linkages in glycogen
B)formation of ( $\alpha$ 1 $\rightarrow$ 4)linkages in glycogen.
C)formation of ( $\alpha$ 1 $\rightarrow$ 6)linkages during glycogen synthesis.
D)glycogen degradation in tree branches.
E)removal of unneeded glucose residues at the ends of branches.

Question 9

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.

Question 10

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.

Question 11

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.

Question 12

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.

Question 13

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
E)FOXO1

Question 14

The enzyme glycogen phosphorylase:

A)catalyzes a cleavage of $\beta$ (1 $\rightarrow$ 4)bonds.
B)catalyzes a hydrolytic cleavage of $\alpha$ (1 $\rightarrow$ 4)bonds.
C)is a substrate for a kinase.
D)uses glucose 6-phosphate as a substrate.
E)uses glucose as a substrate.

Question 15

Glycogen is converted to monosaccharide units by:

A)glucokinase.
B)glucose-6-phosphatase
C)glycogen phosphorylase.
D)glycogen synthase.
E)glycogenase.

Question 16

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.

Question 17

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

Question 18

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

Question 19

For an enzyme to effectively change its activity in response to a change in substrate concentration,it is most favorable for:

A)K_m to be less than cellular substrate concentrations.
B)K_m to be equal to cellular substrate concentrations.
C)K_m to be greater than cellular substrate concentrations.
D)V_max to be at the diffusion limit.
E)The substrate to also be an allosteric effector.

Question 20

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

Question 21

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?

Question 22

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?

Question 23

Explain why reactions that are far from equilibrium need to be regulated.

Question 24

Briefly outline the pathway by which glucose activates the synthesis of pyruvate kinase.

Question 25

Why is citrate,in addition to being a metabolic intermediate in aerobic oxidation of fuels,an important control molecule for a variety of enzymes?

Question 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

Question 27

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 ( $\alpha$ 1 $\rightarrow$ 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 ( $\alpha$ 1 $\rightarrow$ 6)bonds.
E)The enzyme has measurable activity only in liver.

Question 28

Briefly explain the differences between the flux control,elasticity,and response coefficients.

Question 29

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.

Question 30

Explain the distinction between metabolic "regulation" and metabolic "control" in a multienzyme pathway.

Question 31

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?

Question 32

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).

Question 33

Glycogenin:

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.

Question 34

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.

Question 35

Why is it important for proper cell function that proteins turn over rather than persisting indefinitely after being synthesized?

Question 36

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.

Question 37

Which of the following statements is true of muscle glycogen phosphorylase?

A)It catalyzes phosphorolysis of the ( $\alpha$ 1 $\rightarrow$ 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.

Question 38

Explain the difference between homeostasis and equilibrium.

Question 39

Glycogen phosphorylase a can be inhibited at an allosteric site by:

A)AMP.
B)calcium.
C)GDP.
D)glucagon.
E)glucose.

Question 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).

Question 41

What is the biological advantage of synthesizing glycogen with many branches?

Question 42

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

Question 43

Diagram the pathway from glucose to glycogen;show the participation of cofactors and name the enzymes involved.

Question 44

Glycogen synthesis and glycogen breakdown are catalyzed by separate enzymes.Contrast the reactions in terms of substrate,cofactors (if any),and regulation.

Question 45

Explain the role of glycogenin.

Question 46

Show the reaction catalyzed by glycogen synthase.

Question 47

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

Question 48

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.