Chapter 17 Gluconeogenesis
Matching Questions
Use the following to answer questions 1-10:
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Choose the correct answer from the list below. Not all of the answers will be used.
a) liver
b) muscle
c) one day
d) endoplasmic reticulum
e) gluconeogenesis
f) phosphoenolpyruvate carboxykinase
g) PFK-2
h) Cori
i) fructose 2,6-bisphosphate
j) magnesium
k) oxaloacetate
l) biotin
m) 2 hours
n) ATP
1 ____________ This is the process by which noncarbohydrate precursor molecules are converted
into glucose.
Ans: e
Section: Introduction
2 The stores of glucose are enough to support metabolism of a person for how long?
____________
Ans: c
Section: Introduction
3 The major tissue in which gluconeogenesis takes place is ____________.
Th
Ans: a
Section: Introduction
4 The conversion of glucose 6-phosphate to glucose takes place where in the cell? __________
sh
Ans: d
Section: 17.1
5 The reaction that uses GTP and not ATP as its high phosphoryl-transfer potential donor is
____________.
Ans: f
Section: 17.1
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Chapter 17 Gluconeogenesis
2
6 Which compound will activate glycolysis and inhibit gluconeogenesis via conversion of fructose
1,6-bisphosphate? ___________
Ans: i
Section: 17.2
7 ____________ controls the synthesis and degradation of fructose 2,6-bisphosphate.
Ans: g
Section: 17.2
8 ____________ This intermediate is decarboxylated and phosphorylated to produce
phosphoenolpyruvate.
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Ans: k
Section: 17.1
9 ____________ This essential nutrient is required for the carboxylation of pyruvate in humans.
Ans: l
Section: 17.1
10 The ____________ cycle is responsible for converting muscle lactate into glucose in the liver.
Ans: h
Section: 17.3
Fill-in-the-Blank Questions
11 The daily glucose requirement for a typical adult brain is
Ans: 120 g Section: Introduction
.
12 The amount of glucose in the bloodstream and other body fluids is
Ans: 20 g Section: Introduction
13 The process of forming glucose from amino acids is called
Ans: gluconeogenesis
Section: 17.1
.
.
Th
14 Glycerol from fats is modified first by glycerol kinase and then by a second enzyme to enter
gluconeogenesis at
intermediate.
Ans: dihydroxyacetone phophate Section: 17.1
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15 The gluconeogenesis step responsible for reversing pyruvate kinase is
Ans: PEPCK
Section: 17.1
16 Gluconeogenesis is the reversal of steps in glycolysis
Ans: false
Section: 17.1
(true or false).
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.
Chapter 17 Gluconeogenesis
3
17 Some amino acids are converted to glucose via conversion to pyruvate and
Ans: oxaloacetate
Section: 17.1
.
18 The enzyme that carboxylates pyruvate is
.
Ans: pyruvate carboxylate
Section: 17.1
19 The first step of gluconeogenesis takes place in
Ans: mitochondria
Section: 17.1
cellular compartment.
20 ATP in the reaction catalyzed by PEPCK is use to fix
Ans: carbon dioxide
Section: 17.1
21 Transport of oxaloacetate produced by PEPCK utilizes
Ans: Malate dehydrogenase Section: 17.1
to biotin.
mitochondrial and cytosolic enzyme.
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22 AMP will have a(an)
on PFK and a(an)
effect on F-1,6-BPase.
Ans: activating / inhibiting Section: 17.2
23 Allosteric activators of gluconeogenesis are going to
Ans: increase Section: 17.2
the flux of carbon to glucose.
24 The
cycle refers to the metabolic reactions by which glucose is converted into lactate in
skeletal muscle, and then lactate converted back into glucose in the liver.
Ans: Cori Section: 17.3
25 The first step in gluconeogenesis is the
Ans: carboxylation Section:17.1
of pyruvate to form oxaloacetate.
Multiple-Choice Questions
26 Biotin provides __________ for the pyruvate carboxylase reaction.
A)
a long flexible arm for active site location of substrate
B)
carboxylation of pyruvate
C)
group transfer from one site of the enzyme to another
D)
All of the above.
E)
None of the above.
Ans: D Section: 17.1
The phosphoryl donor in the formation of phophoenolpyruvate is:
A)
pyruvate.
B)
PEP.
C)
ATP.
D)
GTP.
E)
inorganic phosphate.
Ans: D Section: 17.1
28
The enzymes involved in shuttling carbons in gluconeogenesis from the mitochondria to the
cytosol are called:
A)
malate dehydrogenase.
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27
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Chapter 17 Gluconeogenesis
B)
C)
D)
E)
Ans:
citrate synthase.
oxaloacetate transferase.
oxaloacetate reductase.
None of the above.
A Section: 17.1
Glucose 6-phosphatase takes place in which cellular location?
A)
cytoplasm
B)
endoplasmic reticulum
C)
mitochondria
D)
nucleus
E)
plasma membrane
Ans: B Section: 17.1
30
High levels of ATP and citrate ___________.
A)
indicate a high energy–well fed state
B)
indicate remote gluconeogenesis
C)
inhibit glycolysis
D)
All of the above.
E)
None of the above.
Ans: D Section: 17.2
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29
31 Phosphofructokinase (PFK) is a highly regulated enzyme. Which of the following statements
about PFK are correct?
A)
AMP and ADP both bind to and stabilize the inactive conformation of F6P.
B)
ATP can overcome the inhibition by citrate.
C)
Citrate is an inhibitor of PFK.
D)
Acidic conditions from anaerobic metabolism activate PFK.
E)
None of the above.
Ans: E Section: 17.2
The bifunctional enzyme is also known as __________.
A)
phosphofructokinase I
B)
phosphofructokinase II
C)
fructose 1-6 phosphatase
D)
protein kinase 2
E)
phosphoenolpyruvate carboxy kinase
Ans: B Section: 17.2
Th
32
Hormonal activation of cyclic AMP levels will:
A)
activate protein kinase A phosphorylation of FBPase2.
B)
phosphorylate PFK2 on a tyrosine residue.
C)
lead to the activation of PFK.
D)
activate the PKC phosphorylation of PFK2.
E)
increase the activation of gluconeogenesis.
Ans: E Section: 17.2
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4
Chapter 17 Gluconeogenesis
5
The major site for gluconeogenesis is in which of the following tissues?
A)
brain
B)
liver
C)
striated muscle
D)
adipose
E)
red blood cells
Ans: B Section: Introduction
35
High blood sugar after a meal _______ the level of insulin released by the pancreas
A)
increases
B)
decreases
C)
has no effect on
D)
chronically activates
E)
chronically inhibits
Ans: A Section: 17.2
36
In general the liver_______________.
A)
will not utilize glucose under starvation/low energy conditions.
B)
acts as a glucose buffer for the rest of the body.
C)
is a producer of glucose for the body under low energy conditions.
D)
All of the above.
E)
None of the above.
Ans: D Section: 17.2 – 17.3
37
Insulin resistance is a hallmark of__________.
A)
PEPCK activation
B)
pancreatic disorder
C)
type 1 diabetes
D)
type 2 diabetes
E)
long-term starvation
Ans: D Section: 17.2
38
Lactate produced in muscle tissue is converted to _________ by __________ .
A)
glucose; gluconeogenesis
B)
lactate; the Cori cycle
C)
glucose; the Cori cycle
D)
pyruvate; glycolysis
E)
ATP; the Krebs cycle
Ans: C Section: 17.2
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34
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39 The primary raw materials for gluconeogenesis are:
A)
galactose and sucrose.
D)
B)
pyruvate and oxaloacetate.
E)
C)
lactate and amino acids.
Ans: C Section: 17.1
fructose and glycerol.
lactose and lactate.
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Chapter 17 Gluconeogenesis
40 How many high-energy phosphate bonds are consumed in gluconeogenesis?
A) three B) six C) two D) four E) one
Ans: B Section: 17.1
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41 What are the thermodynamic constraints on the formation of phosphoenolpyruvate from
pyruvate and how are they overcome in gluconeogenesis?
A)
The ΔG°ˊ for the reverse of the glycolytic reaction for pyruvate kinase is +31 kJ/mol,
which is overcome in gluconeogenesis by the carboxylation/decarboxylation reactions.
B)
The ΔG°ˊ for reverse of the glycolytic reactions for pyruvate kinase is –31 kJ/mol, which
is overcome in gluconeogenesis by the futile cycle enzymes.
C)
The ΔG°ˊ for the reverse of the glycolytic reaction for pyruvate kinase is +0.8 kJ/mol,
which is overcome in gluconeogenesis by the actions of pKa.
D)
The ΔG°ˊ for the reverse of the glycolytic reaction for pyruvate kinase is –0.8 kJ/mol,
which is overcome in gluconeogenesis by the futile cycle reactions.
E)
The ΔG°ˊ for the reverse of the glycolytic reaction for pyruvate kinase is –38 kJ/mol,
which is overcome in gluconeogenesis by the carboxylation/decarboxylation reactions.
Ans: A Section: 17.1
Glycerol, lactate, and amino acids contribute carbon precursors in the formation of glucose;
however, the path that glycerol takes is striking different from the other precursors. Explain how
it differs.
A)
Glycerol is decarboxylated to acetyl CoA and enters gluconeogenesis as pyruvate.
B)
Glycerol enters gluconeogenesis as a breakdown product of triacylglycerols in the form
of dihydroxyacetone phosphate.
C)
Glycerol undergoes a reversible reduction/oxidation reaction to form
phosphoenolpyruvate.
D)
Glycerol is first oxidized in a reaction requiring NAD + and then phosphorylated in
reversible reaction of glycolysis.
E)
Glycerol is oxidized and enters gluconeogenesis as glyceraldehyde phosphate.
Ans: B Section: 17.1
43
What strategy does the liver use to maintain adequate levels of glucose in the blood for use by
other tissues?
A)
Glucose 6-phosphatase has a low KM for glucose 6-phosphate so that glycogen is formed
only when glucose is plentiful.
B)
Transporters named T1, T2, and T3 are responsible for transporting glucose 6-phosphate
in and glucose and inorganic phosphate out of the mitochondrion for gluconeogenesis.
C)
Pyruvate is transported out of the mitochondrion via the oxaloacetate shuttle when
glucose levels in the blood are low.
D)
Glucose 6-phosphatase is bound to the lumen side of the ER where the products of this
enzyme reaction are then transported back to the cytoplasm.
E)
None of the above.
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Ans: D Section: 17.1
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6
Chapter 17 Gluconeogenesis
7
44 What can account for the 1000-fold increase in ATP production when a lot of ATP is needed
such as in intense exercise?
A)
substrate cycles
B)
fructose bisphosphatase 2 activity
C)
phosphorylation of a single serine residue in phosphofructokinase 2
D)
activation of PEPCK
E)
activation of glycedrol kinase
Ans:
Section: 17.2
Short-Answer Questions
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45 Explain how fructose 2,6 bisphosphate is created and degraded in the cell, how the metabolism
of fructose 2,6-bisphosphate is regulated and the effect fructose 2,6 bisphosphate has on
glycolysis and gluconeogenesis
Ans: Discuss the activity of the bifuncitonal enzyme and the regulation of both catalytic
functions of the protein. Once F2,6-BP is produced, relate the effect on PFK1 and
FBPase1 in terms of flux of glucose.
Section: 17.2
46 Eating raw eggs will lead to the ingestion of avidin, a compound that tightly binds to the head
group of biotin. What would be the result of this on a person’s blood sugar level?
Ans: The increase in avidin and decrease in functional biotin would inhibit PEPCK activity
and thus in a starvation state, the blood sugar would remain low.
Section: 17.1
47 What are the key glycolytic enzymes and why are they considered key? How are these steps
overcome in gluconeogenesis?
Ans: pyruvate kinase -> pyruvate carboxylase & phosphoenolpyruvate kinase:
phosphofructokinase -> fructose 1,6-bisphosphatase; hexokinase -> glucose 6phosphatase
Section: 17.1
48 What is the role biotin takes in pyruvate carboxylase catalytic mechanism?
Ans: Biotin is the activated one carbon carrier. The flexible arm of biotin allows the carbon
dioxide to move from one active site of the enzyme to the second set of active site amino
acids where pyruvate is carboxylated.
Section: 17.1
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49 Bumble bees are active when cold while other insects are dormant. This is due to a high rate of
ATP hydrolysis. What might help bring this about?
Ans: Futile cycles that involve ATP hydrolysis, when uncontrolled will result in ATP hydrolysis
to ADP. The inefficient trapping of energy of ATP–ADP results in hyperthermia.
Section: 17.2
50 How does liver restore the level of glucose for active muscles?
Ans: the Cori cycle
Section: 17.3
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Chapter 17 Gluconeogenesis
8
51 How are gluconeogenesis and glycolysis coordinated by nucleotides?
Ans: ATP inhibits glycolysis at PFK, while ADP inhibits the flow of carbon from pyruvate to
glucose at pyruvate carboxylase and phosphoenol pyruvate carboxykinase. When ADP
levels are high, adenylate kinase converts ADP to AMP and ATP. The increase in AMP
(only in a low energy state) results in the inhibition of gluconeogenesis and activates
glycolysis in the liver.
Section: 17.2
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52 The mitochondrial inner membrane is very tight. This means that only a few compounds may
permeate the membrane without a transporter. Oxaloacetate and NADH are two such
compounds. In this light, how can gluconeogenesis continue?
Ans: The four carbon compound oxaloacetate is converted to malate by the mitochondrial
enzyme of MDH producing NAD+ form NADH. There is a malate transporter in the
mitochondrial membrane. Once in the cytosol the reverse reaction is catalyzed by the
cytoplasmic isoform of MDH. The balance in carbon transferred and reducing
equivalents are balanced.
Section: 17.2
53 Which metabolic steps differ from glycolysis in gluconeogenesis?
Ans: There are three irreversible steps in glycolysis, which require four different steps in
gluconeogenesis: pyruvate conversion to phosphoenolpyruvate via an oxaloacetate
intermediate, fructose 1,6-bisphosphate hydrolysis, and the hydrolysis of glucose 6phosphate.
Section: 17.1
54 How are gluconeogenesis and glycolysis regulated reciprocally?
Ans: The enzymes involved in two substrate cycles are control points. Figure 17.6 in the text
shows the glycolytic path activation by F-2,6-BP, AMP, and F-1,6-BP; whereas ATP,
alanine, citrate, and protons inhibit glycolysis. Gluconeogenesis is activated by citrate and
acetyl CoA and inhibited by F-2,6-BP, AMP, and ADP.
Section: 17.2
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55 What role do citric acid cycle intermediates play in the regulation of gluconeogenesis and
glycolysis?
Ans: PFK is inhibited by citrate whereas fructose 1,6 bisphosphatase is activated by citrate.
Acetyl CoA, needed for the condensation with oxaloacetate to form citrate, activates
pyruvate carboxylase.
Section: 17.2
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