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Unit 5: Glucose metabolism and glucose homeostasis

Study Questions and Answers

1. Which statement (if any) about facilitated transporters and enzymes is FALSE?
Both transporters and enzymes

A. are characterized by Km and Vmax values.


B. catalyze chemical reactions.
C. have an active site in which a substrate or ligand is bound.
D. may be located in membranes.

Answer B
This question asks you to compare and contrast enzymes with facilitated transporters,
e.g. the GLUT family of glucose transporters. You should know that both are
characterized by Km and Vmax values. Thus A is TRUE. Remembering David
Lawrence’s discussion of enzymes, you can recall that the presence of a Km and a
Vmax value suggests that a binding site exists and that the site is saturable with ligand
or substrate. Thus C is TRUE. GLUTs can be associated with membranes and you
should be able to think of some enzymes that are membrane-associated (e.g. CPTI and
CPTII). Thus D is TRUE. Although enzymes, by definition, catalyze chemical
conversions, facilitated transporters do not. Facilitated transporters bring about the
change in location of a ligand but do not catalyze chemical change in the ligand. Thus B
is FALSE.

2. In glycolysis the synthesis of ATP is catalyzed by

A. glyceraldehyde 3-phosphate dehydrogenase.


B. hexokinase.
C. phosphofructokinase-1 (PFK-1).
D. phosphoglycerate kinase.
E. NONE of the above catalyze a reaction in which ATP is synthesized.

Answer D

This question is likely to elicit the “memorize to survive” G-protein coupled signal
response. If you memorized the reactions of glycolysis, you’d know that D is the correct
answer. Alternatively, you could see the question as a test about enzyme names.
Dehydrogenases are enzymes that engage in changes in oxidation and usually require
flavin or pyridine nucleotide cofactors. Thus, A is unlikely to be correct. Choices B-D are
kinases, enzymes that utilize high energy phosphates as substrates or products. Your
problem is to ascertain (remember) whether the high energy phosphate is the product or
the substrate in the conventional reactions of glycolysis. Choices B and C result in
phosphorylated sugars, indicating that ATP is a substrate. Choice D, although called a
“kinase”, favors synthesis of ATP because the substrate, 1,3-bisphosphoglycerate, is a
compound of group transfer potential higher than ATP and thus is the correct answer.

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3. The occurrence of the pentose phosphate pathway in hepatocytes is significant
for all of the following EXCEPT synthesis of

A. fatty acids from acetyl CoA


B. glucose from pyruvate
C. nucleotides
D. triacylglycerides from glucose

Answer B
To answer this question ask yourself, “What is the metabolic significance of the pentose
phosphate pathway?” Your answer could be “production of NADPH or production of 5-
carbon sugars that are precursors of ribose and ribonucleotides”. Right away you see
that C is related to the PPP and not a correct answer. For the other choices, you need
to know if NADPH is required. Choices A and D involve fatty acid synthesis, either
directly (A) or indirectly (D) through conversion of glucose to acetyl CoA then to fatty
acids. Choice B is gluconeogenesis, which does not require NADPH and is therefore
the correct answer. This question could be answered more easily from Unit 6.

4. Which organ has the highest demand for glucose per gram of tissue?
A. brain
B. cardiac muscle
C. liver
D. pancreas
E. skeletal muscle

Answer A
This is just one of those facts you need to know. The preferred fuel of brain is glucose.
Brain is unable to utilize fatty acids as a fuel to any significant degree. Brain can also
utilize ketone bodies as a fuel but this question doesn’t ask about ketone bodies.

5. The human liver cannot produce glucose from


A. pyruvate.
B. even chain fatty acids.
C. alanine.
D. lactate.
E. Glucose can be made from ALL the above precursors in human liver.

Answer B
This question asks you about production of glucose from non carbohydrate compounds
and thus asks you about gluconeogenesis. You should know that pyruvate, alanine and
lactate are “gluconeogenic precursors”, i.e. are compounds that can enter the pathways
of gluconeogenesis at some point for net production of glucose. Answering the question

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thus hinges on knowing if even chain fatty acids can be converted into glucose, in which
case E is correct, or cannot be converted into glucose, in which case B is correct. Fatty
acids with even numbers of carbon atoms can be converted entirely to acetyl CoA.
Acetyl CoA cannot give net production of glucose. See the last paragraph of “regular
text” on page 561. Odd chain fatty acids can give net production of glucose by
conversion to propionyl CoA and then into succinyl CoA and then into the TCA cycle,
discussed in the next to last paragraph on page 561.

6. A common intermediate in the conversion of glycerol and lactate to glucose is


A. glucose 6-phosphate.
B. glycerol 3-phosphate.
C. malate.
D. oxaloacetate.
E. phosphoenolpyruvate
F. pyruvate.

Answer A
This question also asks about your understanding of gluconeogenesis since it asks
about conversion of glycerol and lactate to glucose. Picture the scheme of
gluconeogenesis. Visualize where glycerol and lactate enter into the scheme of
gluconeogenesis. Then determine what compound occurs after the point where glycerol
and lactate enter. You should remember that lactate enters by conversion to pyruvate.
You then note that C through E are precursors of pyruvate in the scheme of
gluconeogenesis, i.e. precede pyruvate. Thus, C through F are in or precede the
gluconeogenic branch for lactate and cannot be in common with the branch for glycerol.
You need to know that glycerol enters the scheme by conversion to glycerol 3-
phosphate then to dihydroxyacetone phosphate. Thus B is found only in the branch for
glycerol. This leaves A, the penultimate compound before glucose, as common to both
the glycerol and lactate branches of gluconeogenesis.

7. When the ratio of plasma insulin:glucagon decreases, the activity of this hepatic
enzyme decreases.
A. adenylate cyclase
B. fructose 1,6-bisphosphatase
C. hexokinase
D. the kinase activity of phosphofructokinase-2
E. protein kinase A

Answer D
Before answering questions like this you are advised to take a deep breath, then
exhale. First recognize that hexokinase, C, is not a hepatic enzyme and therefore
cannot be an answer. I find it convenient to determine the change in the given enzymes,

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A to E, under a given change in insulin or glucagon that givesthe specified decrease in
the insulin:glucagon ratio.

E.g. you could consider an increase in glucagon then predict


A ↑
B ↑
D ↓
E ↑

This identifiesD as the correct answer.

8. Patients with McArdle’s disease, a glycogen storage disease, have a deficiency


of muscle glycogen phosphorylase yet do not typically suffer hypoglycemia on
fasting. From this information, you would predict that McArdle’s patients
A. do not respond to glucagon in a normal fashion.
B. show defect(s) in the synthesis of muscle glycogen.
C. have defect(s) in one or more tricarboxylic acid cycle enzyme(s) in
muscle.
D. produce less lactic acid during exercise because lactate is more efficiently
converted to pyruvate in muscle.
E. show reduced flow of metabolites through the muscle glycolytic pathway
during exercise.

Answer E
You know immediately that A is incorrect because muscle lacks a receptor for glucagon.
A deficiency in muscle glycogen phosphorylase will produce a defect in degradation of
muscle glycogen. Thus B and C are incorrect because synthesis of muscle glycogen
and muscle TCA enzymes are not expected to be affected. Choice D does not make
metabolic sense. It is difficult to connect a deficiency of glycogen phosphorylase with an
effect on lactate-to-pyruvate conversion. This leaves E. Choice E makes sense. If there
is a deficiency in breakdown of muscle glycogen to glucose 6-phosphate, then you’d
expect less flow of metabolites through the glycolytic pathway in muscle.

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