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BIOCHEMISTRY 460
FOURTH HOUR EXAMINATION
FORM A (YELLOW)
ANSWER KEY
May 5, 2004
A CALCULATOR MAY BE USED ON THIS EXAM. IF YOUR CALCULATOR IS
PROGRAMMABLE, ALL MEMORY BANKS MUST BE CLEARED BEFORE YOU ENTER
THE EXAM, AND WE MAY CHECK & CLEAR CALCULATORS DURING THE EXAM.
SHOW YOUR WORK FOR ALL CALCULATIONS, AND BE SURE TO STATE UNITS OF ANY
NUMERICAL ANSWERS. If the reasoning, calculations, or answer are shown anywhere other
than in the space provided, make a note in the space provided and put answer on back of SAME
PAGE so the grader for that page will have it.
USEFUL CONSTANTS:
R (gas constant) = 8.315 x 10–3 kJ•mol–1•Kelvin–1
F (Faraday constant) = 96.48 kJ•Volt–1•mol–1
If temperature = 25 °C, absolute temperature T = 298 ºK
Biochemistry 460, Exam #4 Form A ANSWERS
May 5, 2004
1.
NAME
4-digit course ID#
(3 pts) What metabolic intermediate is both a product of the glycogen phosphorylase reaction and is
also involved in glycogen synthesis?
Glucose-1-phosphate (glucose-1-P)
2.
(7 pts)
A. (4 pts) The conversion of phosphoenolpyruvate to pyruvate in the cytosol is an exergonic
reaction catalyzed by the enzyme pyruvate kinase (ΔGº' = -31.4 kJ/mol). Since the reverse of this
reaction is highly unfavorable (ΔGº' = +31.4 kJ/mol), explain how it is possible that the conversion of
pyruvate to phosphoenolpyruvate in the gluconeogenic pathway is found to be exergonic (ΔGº' = 22.6 kJ/mol)?
The conversion of pyruvate to phosphoenolpyruvate utilizes two different enzymes (pyruvate
carboxylase and phosphoenolypyruvate carboxykinase), each of which require hydrolysis of a
high energy phosphate bond in a coupled reaction with ATP (GTP).
B. (3 pts) Does this part of the gluconeogenic pathway occur in the mitochondrial matrix or the
cytosol?
One of the reactions takes place in the mitochondria (pyruvate carboxylase) and one occurs in
the cytosol (phosphoenolypyruvate carboxykinase).
3.
(5 pts)
A. (3 pts) Name the gluconeogenic enzyme that catalyzes the bypass reaction in glycolysis
catalyzed by phosphofructokinase (i.e., what gluconeogenic enzyme opposes phosphofructokinase).
Fructose 1,6-bisphosphatase
B. (2 pts) Does AMP activate (+) or inhibit (-) this gluconeogenic enzyme?
AMP inhibits fructose 1,6-bisphosphatase
4.
(5 pts) Von Gierke's disease is due to a deficiency in the enzyme glucose-6-phosphatase. Why do
individuals with this disease release a small amount of glucose into the blood after injection with a
high dose of glucagon?
Glucagon stimulates glycogen breakdown and the product of debranching enzyme is free
glucose which is released into the blood.
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Biochemistry 460, Exam #4 Form A ANSWERS
May 5, 2004
NAME
4-digit course ID#
5. (4 pts) Glycogen phosphorylase b activity is regulated by: (circle the one best answer)
a.
b.
c.
d.
e.
f.
6.
phosphorylation of serine residues in the dimer, shifting the equilibrium to the R state.
low energy charge leading to allosteric activation, shifting the equilibrium to the R state.
dephosphorylation of serine residues in the dimer, shifting the equilibrium to the T state.
high ATP levels leading to allosteric inhibition, shifting the equilibrium to the T state.
All of the above.
None of the above.
(6 pts) Fill in the blanks in the two sentences below with the most correct words:
Epinephrine (hormone) activates a signaling pathway in liver cells controlled by protein kinase A
(enzyme) that results in the phosphorylation of enzymes leading to the stimulation of glycogen
degradation (process).
Insulin (hormone) signaling activates a pathway in liver cells controlled by protein phosphatase 1
that results in dephosphorylation (modification) of enzymes leading to the stimulation of glycogen
synthesis (process).
7.
(5 pts) When the energy charge in liver cells is low, and oxaloacetate levels are limiting, what is the
fate of excess mitochondrial acetyl CoA? Name a physiological condition that causes this.
Excess acetyl CoA is converted to ketone bodies.
Ketone bodies are produced as a result of starvation (or diabetes).
8.
(5 pts) By what general mechanism of enzyme regulation does citrate control acetyl CoA
carboxylase activity? Does citrate activate or inhibit acetyl CoA carboxylase ? Explain your answer
in terms of metabolic needs of the cell.
Citrate activates acetyl CoA carboxylase by the mechanism of allosteric control. This makes
sense because when cytosolic citrate levels are high, it signals that the mitochondrial matrix is
not utilizing excess citrate (or acetyl CoA) and therefore it is time to store energy as fat.
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Biochemistry 460, Exam #4 Form A ANSWERS
May 5, 2004
9.
NAME
4-digit course ID#
(5 pts) As shown in the diagram at the right, Olestra is a fat substitute composed of a sucrose
molecule covalently linked to several fatty acids.
A. (2 pts) Why is this fat substitute considered a zero calorie fat molecule?
Because pancreatic lipase does not recognize Olestra as a substrate and it passes through the
body without giving up its fatty acid components for energy storage.
B. (3 pts) Why does Olestra prevent the dietary
absorption of fat soluble vitamins?
Fat-soluble vitamins associate with the hydrophobic
fatty acids and are excreted.
10. (5 pts) The hump of a camel contains over 10 kilograms of triglycerides, much of which is
metabolized during long journeys across the desert. Explain why the camel's hump permits it to
survive for extended periods of time without drinking water.
Oxidation of fatty acids generates large amounts of H2O.
11. (5 pts) What is the biochemical basis for improved anti-inflammatory action and reduced stomach
bleeding in individuals taking the COX-2 inhibitor Celebrex as compared to aspirin or ibuprofen?
Celebrex has a high affinity for the active site of COX-2, but is too large to bind to COX-1.
Aspirin is a relatively small molecule that binds to and inactivates both COX-1 and COX-2.
COX-1 is an enzyme that protects the stomach lining from damage due to the acidic
environment and therefore aspirin causes stomach bleeding but Celebrex does not.
12. (5 pts) In order to control blood cholesterol levels, would it be better to develop pharmacologic
therapies that up-regulate or down-regulate low density lipoprotein (LDL) receptor levels in liver
cells? Explain your answer.
It would better to up-regulate LDL receptor expression in liver cells because LDL receptors
import lipoprotein particles containing cholesterol into liver cells, and thereby lower blood
cholesterol levels.
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Biochemistry 460, Exam #4 Form A ANSWERS
May 5, 2004
NAME
4-digit course ID#
13. (5 pts) Explain why tyrosine is considered a non-essential amino acid even though humans lack the
enzymes required for de novo tyrosine biosynthesis.
Tyrosine is considered a non-essential amino acid because humans contain an enzyme
(phenylalanine hydroxylase) that converts the essential amino acid phenylalanine to tyrosine.
14. (5 pts) Why does it take up to 7 days before there are any noticeable herbicidal effects of glyphosate?
Because it takes that long before the plant uses up all available phenylalanine and becomes
dependent on the de novo pathway for phenylalanine biosynthesis.
15. (5 pts) Explain how the amino group of alanine can be incorporated into urea without first being
+
converted to NH4 by the enzyme glutamate dehydrogenase. Name the type of enzyme required for
this reaction to occur.
The amino group of alanine is transferred to glutamate by an aminotransferase enzyme
(alanine amino transferase) which in turn donates the amino group to aspartate by a second
aminotransferase (aspartate aminotransferase). The amino group from aspartate is
incorporated into urea by the urea cycle.
16. (5 pts) What is fundamentally different about the metabolic diseases albinism and phenylketonuria
(PKU) with regard to the underlying cause of the disease symptoms in terms of substrates and
products of the affected enzymatic reaction?
Albinism is due to lack of the reaction product (pigments are not produced), whereas, PKU is
due to accumulation of substrate (phenylalanine).
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Biochemistry 460, Exam #4 Form A ANSWERS
May 5, 2004
NAME
4-digit course ID#
17. (10 pts) Identify each of the ten
biomolecules that are missing
from the metabolic map by
writing the name or chemical
abbreviation next to the
corresponding numbers below.
1. ___ lipid(s)__
2. ___ amino acids __
3. ___ glucose _____
4. ___ fatty acids __
5. ___ pyruvate___
6. ___ acetyl CoA _
7. _ CO2 (carbon dioxide) __
8. ____ NADH _____
9. ____ ATP _______
10. ___ H2O (water) ___
18.
(5 pts) What hormonal response explains why it is a bad idea to eat a candy bar with high sugar
content prior to a bicycle race in which the cyclist's metabolic needs will be dependent on stored fats
for energy?
Eating a candy bar will cause an sharp rise in insulin levels and lead to inhibition of fatty acid
oxidation which is needed later in the race to provide energy to muscle cells.
19. (5 pts) Explain why giving an insulin injection to a diabetic individual three hours after the start of a
glucose tolerance test can be used to distinguish between type 1 and type 2 diabetes.
Type 1 diabetes is characterized by lack of insulin production, whereas, Type 2 diabetes is due to
defects in the ability to respond to insulin. Therefore, if the patient's glucose levels dropped after
insulin injection, they most likely have Type 1 diabetes, if the glucose levels do not drop, then they
more likely have Type 2 diabetes.
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