isites Hypotonia

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1. (5 pts) The free-energy change for the formation of Compound C from the Reactants A and B is
   positive and is thus an endergonic reaction. How, then, do cells accomplish the production of
   Compound C?

2. (5pts) The citric acid cycle is frequently described as the major pathway of aerobic catabolism,
which means that it is an oxygen-dependent degradative process. However, none of the reactions of
the cycle directly involves oxygen as a reactant. Why is the pathway oxygen-dependent?

3. (5 pts) What system is necessary to transport fatty acyl-CoA into mitochondria?

4. (5 pts) In the movie Jurassic Park, the scientists “engineer” the dinosaurs with a faulty gene so that
they cannot synthesize lysine and are dependent on tablet supplements. What is the fault with this
5. (15 pts) Your patient is a 2-year-old male infant named Justin N. He is suffering from hypotonia,
weakness and growth failure, and is unable to walk. X-rays indicate that the infant is suffering from
rickets, which is a result of a nutritional deficiency of Vitamin D. But the infant’s mother insists that
her son’s diet is not Vitamin D-deficient. He drinks three glasses of milk a day, and his diet also
includes meat and eggs. You decide to carry out further analysis and take a sample of the infant’s
blood. The laboratory results are shown in Table below.

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A simplified scheme of Vitamin D metabolism is shown in Figure 1. The two main sources of active
Vitamin D are diet and sunlight. Food supplemented with “Vitamin D” usually contains
cholecalciferol (Vitamin D3), or possibly a biologically equivalent analog. In the liver, dietary
cholecalciferol is converted to 25-hydroxycholecalciferol. Next, in the kidney, the 25-
hydroxycholecalciferol is converted to the active Vitamin D (1,25-dihydroxycholecalciferol).

Sunlight is also responsible for producing Vitamin D3. The skin contains a precursor, 7-
dehydrocholesterol. In the presence of ultraviolet light, which acts as a catalyst, a
ring-opening reaction occurs which is followed by the spontaneous conversion of this intermediate to
Vitamin D3. Vitamin D3 is then converted to active Vitamin D via the pathway just described.

A. (10 pts) After obtaining the results from the laboratory, you suspect that your patient might have a
defective enzyme in the Vitamin D synthetic pathway. Which enzyme do you think is defective, and

B. (5 pts) How does a deficiency in Vitamin D result in the development of rickets, a disease
characterized by the softening of bone which can results in deformations and easy breakage?
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Figure 1 – Vitamin D Metabolism.
6. (19 pts ) The Eastern skunk cabbage has the ability to maintain its temperature 15-35 C higher
than ambient temperatures during the months of February and March, which is critical to the survival
of the plant since the flowering tissue is not frost-resistant. The mechanisms of thermogenesis in
plants are not well understood but the recent discovery of a protein uncoupler in the potato along with
observed changes in oxygen consumption during periods of cold suggest a mechanism similar to that
of the uncoupling agents in brown fat in mammals.

A. (10 pts) Explain how uncoupling agents work and how an uncoupling agent acts to bring about an
increase in temperature.

B. (5 pts) In the skunk cabbage, the site of thermogenesis is in the flowering tissues. These tissues do
not store starch but massive starch stores are found in the root systems. Why is starch required for

C. (4 pts) Oxygen consumption by the skunk cabbage increases as temperature decreases. The rate
of oxygen consumption nearly doubles with every 10 •C drop in ambient temperature. Explain the
biochemical mechanism for these observations.
Bonus 2 pts
In the skunk cabbage, thermogenesis occurs because of the action of an uncoupling protein that may
be similar to the newly identified uncoupling protein in the potato. The regulation of this protein is
being studied and the results from one such experiment are shown in the figure below. What do the
data suggest about the regulation the uncoupling protein?

Figure 2: Northern blot analysis of the uncoupling protein
from potatoes at 20•C and 4•C. Northern blots detect levels of
mRNA (based on Laloi, et al., 1997).

Laloi, M., Klein, M., Riesmeier, Müller-Röber, B., Fleury, C, Bouillaud and Ricquier, D. (1997) Nature 389, pp. 135-136.
Knutson, R. M. (1974) Science, 186, pp. 746-747.
Seymour, R. S., and Schultze-Motel, P. (1996) Nature, 383, p. 305.


7. (50 pts) Phenylketonuria (PKU) is an inherited disease that results from the lack of the enzyme
phenylalanine hydroxylase (PAH). PAH catalyzes the first step in the degradation of phenylalanine
(See figure 3 below). In the phenylketonuric patient, the phenylalanine that accumulates is
eventually transaminated to phenylpyruvate, a phenylketone compound. Excess phenylpyruvate
accumulates in the blood and urine resulting in cognitive defects if left untreated. Screening programs
identify PKU babies at birth, and treatment consists of a low phenylalanine diet until maturation of
the brain is completed.

A. (10 pts ) Is phenylalanine glucogenic, ketogenic, or both? Explain.

B. (5 pts) Tyrosine is not typically an essential amino acid but it is essential in persons with PKU.

C. (5 pts) Patients with the disease PKU tend to have blue eyes, fair hair, and very light skin. Why?

D. (5 pts) Why is a PKU patient placed on a low phenylalanine diet instead of a phenylalanine free
E. ( 6 pts) The artificial sweetener Nutrasweet ® contains the compound aspartame, which consists
of a methylated Asp-Phe dipeptide. (The C-terminal carboxyl group is methylated.) Draw the
structure of aspartame. Should a manufacturer place a warning for PKU patients on products
containing aspartame? Why or why not?

F. ( 20 pts) The PAH enzyme has been isolated and its regulation investigated. To determine if
phenylalanine, in addition to serving as a substrate for the enzyme, is playing a role in PAH
regulation the following experiments were performed: A. Polyacrlyamide gel electrophoresis under
denaturing and non-denaturing conditions, B. kinetic studies, and C. activity assays. The results are
shown below.


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                                                                          Preincubation    --   +
                                                Substrate concentration   with Phe

What do the data suggest about the role, if any, of phenylalanine in the regulation of PAH activity.
Be sure to include a description of the data in your answer.
                                                Substrate concentration
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Figure 3 - Phenylalanine and tyrosine metabolism. BH4 tetrahydrobiopterin, an essential
cofactor for phenylalanine hydroxylase.

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