Glycogen is converted to monosaccharide units by:
A) glucokinase.
B) glucose-6-phosphatase
C) glycogen phosphorylase.
D) glycogen synthase.
E) glycogenase.
C) glycogen phosphorylase.
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 un
C) formation of (?1 ? 6) linkages during glycogen synthesis.
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 sy
D) is the primer on which new glycogen chains are initiated.
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-phosp
B) It catalyzes addition of glucose residues to the nonreducing end of a glycogen chain by formation
of (?1 ? 4) bonds.
Which one of the following statements abour 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
E) This enzyme adds the initial glucose unit to a tyrosine residue in glycogenin.
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.
B) catalyzes a hydrolytic cleavage of (?1 ? 4) bonds.
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 o
B) maintaining a constant supply and concentration of ATP.
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 e
C) the reaction will go backward and be exergonic.
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
A) Activation by cleavage of an inactive zymogen
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 pa
D) 1, 3, 4
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.
B) high concentrations of ATP.
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 n
C) The conversion of fructose 1,6-bisphosphate to fructose 6-phosphate is not catalyzed by
phosphofructokinase-1, the enzyme involved in glycolysis.
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 activate
D) The phosphofructokinase-1 reaction is endergonic.
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 degrade
D) It exists in an active (a) form and an inactive (b) form that is allosterically regulated by AMP.
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 glyc
A) Phosphorylation activates the enzyme responsible for breakdown, and inactivates the synthetic
enzyme.
Glycogen phosphorylase a can be inhibited at an allosteric site by:
A) AMP.
B) calcium.
C) GDP.
D) glucagon.
E) glucose.
E) glucose.
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 kinas
B) Dephosphorylation of multiple residues by phosphoprotein phosphorylase-1 (PP1)
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 a
E) PP1 is phosphorylated by glycogen synthase kinase-3 (GSK3).
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 pre
E) all of the above.
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.
E) both B and C.
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).
Muscle glycogen consists of linear polymers of (?1 ? 4)-linked D-glucose, with many branches formed by (?1 ? 6) glycosidic linkages to D-glucose. Glycogen phosphorylase in muscle
catalyzes phosphorolytic cleavage of the terminal residue at the nonreducing ends, producing glucose 1-phosphate. When phosphorylase approaches (?1 ? 6) branch points, a second enzyme (the
"debranching enzyme") transfers three glucose residues nearest the branch point and reattaches them in (?1 ? 4) linkage at a nonreducing end via transferase activity. Then employs its glucosidase activity to remove the glucose moiety at the (?1 ? 6) branch point. Now phosphorylase can continue to degrade the molecule.
Glycogen synthesis and glycogen breakdown are catalyzed by separate enzymes. Contrast the
reactions in terms of substrate, cofactors (if any), and regulation.
Glycogen synthesis is catalyzed by glycogen synthase and employs UDP-glucose as the
activated precursor:
UDP-glucose + glycogen (glucose)n ? UDP + glycogen (glucose)n+1
Glycogen synthase is inactivated by phosphorylation, catalyzed by cAMP-dependent protein kinase;
it is activated by dephosphorylation, catalyzed by phosphoprotein phosphatase. Glycogen breakdown
is catalyzed by glycogen phosphorylase, which employs pyridoxal phosphate (PLP) as a cofactor.
The reaction is a phosphorolysis; the glycosidic bond is broken by the attack of Pi:
Glycogen (glucose)n + Pi ? glycogen (glucose)n -1 + glucose 1-phosphate.
Glycogen phosphorylase is activated by phosphorylation, catalyzed by phosphorylase kinase, and it is
inactivated by dephosphorylation, catalyzed by phosphorylase a phosphatase.
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.
To enter glycolysis, glucose-1-phosphate must undergo isomerization to glucose-6-phosphate
by phosphoglucomutase. To replenish glucose in the bloodstream, glucose-1-phosphate must be
hydrolyzed to free glucose by glucose-1-phosphatase.
Diagram the pathway from glucose to glycogen; show the participation of cofactors and name the
enzymes involved.
(1) Glucose + ATP ? glucose 6-phosphate + ADP
enzyme: hexokinase
(2) Glucose 6-phosphate ? glucose 1-phosphate
enzyme: phosphoglucomutase
(3) Glucose 1-phosphate + UTP ? UDP-glucose + PPi
enzyme: UDP-glucose pyrophosphorylase
(4) UDP-glucose ? glycogen + UDP
enzyme: glycogen synthase
Show the reaction catalyzed by glycogen synthase.
The reaction is the addition of a glucose moiety from UDP-glucose to the nonreducing end of a
glycogen chain; the linkage formed is (?1 ? 4).
What is the biological advantage of synthesizing glycogen with many branches?
Highly branched glycogen is more soluble than unbranched glycogen. In addition, both
glycogen synthase and glycogen phosphorylase act at the nonreducing ends of glycogen chains.
Branched glycogen has far more ends for these enzymes to work on than would the equivalent
amount of linear glycogen chains. Having more ends effectively increases the concentration of
substrate for the enzymes, thereby increasing the rate of glycogen synthesis and breakdown.
Show all of the reactions that occur in the pathway from galactose to glycogen in an adult human.
You do not need to give structures or name enzymes; just name the intermediates along the path and
show any required cofactors.
(1) Galactose + ATP ? Galactose 1-phosphate + ADP
(2) Galactose 1-phosphate + UDP-glucose ? UDP-galactose + glucose 1-phosphate
(3) UDP-galactose ? UDP-glucose (catalyzed by UDP-glucose epimerase, which requires NAD+)
(4) UDP-glucose + glycogen (glucose)n ? UDP + glycogen (glucose)n +1
Explain the role of glycogenin.
Glycogenin is a protein that acts as the "primer" for the initiation of new glycogen molecules. It catalyzes the transfer of a glucose residue from UDP-glucose to a tyrosine hydroxyl group in glycogenin, then forms a complex with glycogen synthase. As more glucose residues are added, this first glucose residue, still attached to glycogenin, becomes the reducing end of the growing glycogen
chain.
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?
Normally, [ATP] is 5-10 mM, while [AMP] is < 0.1 mM, thus AMP is a much more sensitive indicator of a cell's energetic state. Small changes in ATP concentration are amplified into large changes in AMP concentration (see Table 15-1), hence many regulatory processes hinge on changes in the concentration of AMP.
Describe four major principles of metabolic regulation that have selectively evolved throughout
evolution.
1. Maximize the efficiency of fuel utilization by preventing the simultaneous operation of
opposing pathways (i.e., futile cycles). 2. Partition metabolites appropriately between alternative
pathways. 3. Draw on the fuel best suited for the immediate needs of the organism. 4. Shut down
biosynthetic pathways when their products accumulate.
In the glycolytic path from glucose to phosphoenolpyruvate, two 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 cat
The two irreversible steps in glycolysis are conversion of glucose to glucose 6-phosphate, catalyzed by hexokinase, and conversion of fructose 6-phosphate to fructose 1,6-bisphosphate, catalyzed by phosphofructokinase-1. The first reaction is bypassed during
gluconeogenesis by the reaction catalyzed by glucose 6-phosphatase, an enzyme unique to the liver.
The second is bypassed by fructose 1,6-bisphosphatase-1 (FBPase-1). By having separate pathways that employ different enzymes, an organism is able to control anabolic and catabolic processes
separately, thus avoiding futile cycles. A potential disadvantage is the need to produce separate sets of enzymes for catabolism and anabolism.
Why is citrate, in addition to being a metabolic intermediate in aerobic oxidation of fuels, an
important control molecule for a variety of enzymes?
As the key biochemical intermediate in the citric acid cycle resulting from the condensation of
oxaloacetate and acetyl-CoA, citrate is at a junction of amino acid, fatty acid, and pyruvate oxidation,
serving as an intracellular signal that the cell's current energy needs are being met. In particular, it is
an allosteric regulator of PFK-1, increasing the inhibitory effect of ATP, and further reducing the
flow of glucose through glycolysis.
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?
Glucagon, signaling low blood sugar, stimulates cAMP synthesis, which activates protein
kinase A (PKA) to phosphorylate PFK-2/FBPase-2 (among other proteins). This phosphorylation
enhances FBPase-2 activity and inhibits PFK-2 activity of the enzyme, resulting in lower levels of
fructose 2,6-bisphosphate (F26BP). In the absence of F26BP as an allosteric effector, the activity of
PFK-1 is reduced (inhibiting glycolysis) and the activity of FBPase-1 is enhanced (stimulating
gluconeogenesis), thus enabling the liver to replenish blood glucose.
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.
A futile cycle is a pair of reactions or pathways in one of which A is converted into B, and in the
other, B into A. For example, conversion of fructose 6-phosphate into fructose 1,6-bisphosphate
(catalyzed by phosphofructokinase-1) is effectively reversed by the reaction catalyzed by fructose
1,6-bisphosphatase. The sum of the two reactions is the hydrolysis of ATP and the dissipation of
energy as heat, a wasteful process except when the organism needs to generate heat to maintain body
temperature.
Fructose 6-phosphate + ATP ? fructose 1,6-bisphosphate + ADP
Fructose 1,6-bisphosphate ? fructose 6-phosphate + Pi
Sum: ATP ? ADP + Pi (+ heat)
Cells use reciprocal regulation of the pathways such that when a reaction in the pathway in one
direction is stimulated, the reaction in the reverse pathway is inhibited, and vice versa.
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) Stim
The correct temporal order is 5-2-1-4-3.
Explain the distinction between metabolic "regulation" and metabolic "control" in a multienzyme
pathway.
Regulation refers to rebalancing the levels of metabolites along a pathway in response to a change in flux through the pathway, while control is what determines the total flux through the pathway.