Spring 2017 Molecular Medicine Practice Exam 1

1. A 34-year-old male has just tapped out from a wilderness survival contest/reality TV show. The
contestant spent three weeks subsisting on wild plants and the few fish he was able to catch. His fat
stores are almost completely depleted and his body is currently breaking down muscle to use for energy
generation. Which of the following amino acids derived from muscle would his body use to directly
generate pyruvate?

A. Ala
B. Glu
C. Ile
D. Leu
E. Phe

2. Which of the following enzymes would be active in the liver of an alcoholic who has just ingested 12
alcoholic drinks on an empty stomach?

A. Glucokinase
B. Pyruvate dehydrogenase
C. Isocitrate dehydrogenase
D. 3-hydroxyacyl CoA dehydrogenase
E. HMG CoA synthase

3. A 18-year-old male has been on a protein-restricted diet his entire life. Since beginning college he has
decided to try and bulk up with intense weightlifting and protein power supplementation afterwards.
Within the first week of this new regimen he has been rushed to the emergency room after his
roommate found him unconscious. Blood testing shows elevated blood pH and hyperammonemia
present. Abnormally high levels of orotic acid are found. The enzymatic defect responsible for this
condition means the patient is not producing sufficient amounts of

A. Carbamoyl phosphate
B. Citrulline
C. Arginine
D. Aspartate
E. Fumarate
4. The metabolism of ethanol proceeds at a rate that is independent of the amount ingested because

A. The amount of CYP2E1 in the MEOS of hepatocytes cannot be increased

B. The rate by which ethanol enters a cell is fixed
C. The amount of acetaldehyde dehydrogenase present in hepatocytes does not change
D. The rate at which ethanol is transported in the bloodstream is fixed
E. The rate at which acetate is converted to pyruvate is fixed

5. In addition to using niacin to make NAD+, which amino acid can the body use to make NAD+?

A. Trp
B. Met
C. Lys
D. Ser
E. Cys

6. A 6-year-old girl is brought to the pediatrician by her mother for a rash that will not respond to
hydrocortisone. In addition to the rash, the mother indicates the girl has developed diarrhea and has
also complained of headaches since the rash appeared. A urine test reveals abnormally high levels of
several amino acids and the pediatrician recommends increasing protein intake and supplementation
with

A. Thiamine
B. Riboflavin
C. Niacin
D. Vitamin B12
E. Vitamin B6

7. A 43-year-old female who is a chronic alcoholic is complaining of nausea, dizziness, and a rapid
heartbeat (tachycardia). The patient states that she was having “really bad heartburn” and took three
times the normal dose of Tagamet and also had six alcoholic beverages at the same time. The symptoms
are consistent with an overdose of Tagamet, which is likely because

A. The ethanol is out-competing the Tagamet for the MEOS

B. The ethanol is allosterically inhibiting CYP2E1
C. The ethanol is inducing the production of additional CYP2E1
D. The ethanol is allosterically activating CYP2E1
E. The ethanol is increasing absorption of the Tagamet by hepatocytes

8. Experiments on a cancer cell line that cannot effectively metabolize Ser indicate an amino acid
substitution in serine aminotransferase has reduced the enzyme’s Km. An assay to test the activity of
serine amino transferase would require a mixture of serine, serine aminotransferase, and
 A. Pyruvate
B. Oxaloacetate
C. Malate
D. -ketoglutarate
E. Citrulline

9. There are some nomadic cultures that adhere to a meat and dairy diet almost exclusively. During
times of high cellular ADP or AMP levels, which of the following amino acids could be converted to a
compound found in the TCA using only a 1-step reaction?

A. Glu
B. Gln
C. Thr
D. Ile
E. Ser

10. A patient presents with steatorrhea, abdominal pain, and nausea. A stool sample is tested after the
patient ingests a standardized protein serving. Results indicate normal levels of enteropeptidase and a
large percentage of protein in the stool is intact with only minimal degradation/digestion occurring. The
enzyme which is most likely to be functioning normally in the patient is

A. Pepsin
B. Chymostrypsin
C. Trypsin
D. Elastase
E. Carboxypeptidase A

11. A temporary lack of Gln would limit the production of which non-essential amino acid?

A. Ser
B. Asn
C. Cys
D. Tyr
E. Gly
12. Folic acid (folate) metabolism is an area of interest for cancer research and several anti-folates are
used in chemotherapy. In addition to being effective against cancerous cells, these drugs also harm
normal cells and this causes the side-effects associated with these drugs. When anti-folates are
administered and folic acid is of limited availability, which amino acid would no longer be completely
metabolized?

A. Val
B. Ile
C. Met
D. His
E. Phe

13. Lab results suggest the possibility of a defect in either Phe or Tyr metabolism. A follow up test
involves homogenizing a tissue biopsy and adding a mixture of Phe, Tyr, -ketoglutarate, NADH, and
tetrahydrobiopterin. The result is the production of glutamate and p-hydroxyphenylpyruvate and
nothing else. These results suggest the presence of

A. PKU
B. Tyrosinemia I
C. Tyrosinemia II
D. Tyrosinemia III
E. Alkaptonuria

14. An individual with Hartnup disease has made the decision to adopt a vegan diet and has also
stopped taking their niacin supplement due to concerns that it is not vegan-sourced. This dietary change
will reduce their body’s ability to metabolize

A. Ala
B. Glu
C. His
D. Asp
E. Val

15. When ethanol is being metabolized in hepatocytes, the TCA cycle can be shut down due to

A. The action of NADH on isocitrate dehydrogenase

B. The action of acetate on malate dehydrogenase
C. The action of NADPH on citrate synthase
D. The action of ATP on -ketoglutarate dehydrogenase
E. The action of acetyl-CoA on aconitase
16. Patients with Lesch-Nyhan syndrome have hyperuricemia, indicating an increased synthesis of
purine nucleotides and decreased levels of HGPRT activity. The hyperuricemia can be explained on the
basis of a decrease in which regulator of purine biosynthesis?

A. ATP
B. GDP
C. Glutamine
D. IMP
E. PRPP

17. The anticancer drug 6-mercaptopurine is deactivated by the enzyme xanthine oxidase. A cancer
patient being treated with 6-mercaptopurine develops hyperuricemia and the physician decides to give
the patient allopurinol. What effect will allopurinol have on the activity of 6-mercaptopurine?

A. Enhanced deactivation of 6-mercaptopurine

B. Enhanced elimination of 6-mercaptopurine as uric acid
C. Enhanced retention and potentiation of 6-mercaptopurine activity
D. Decreased inhibition of glutamine:phosphoribosylpyrophosphate amidotransferase

18. Resistance of neoplastic cells to the chemotherapeutic effect of 6-mercaptopurine would most likely
involve loss or inactivation of a gene encoding

A. Thymidylate synthase
B. Hypoxanthine-guanine phosphoribosyltransferase
C. Purine nucleoside pyrophosphorylase
D. Orotate phosphoribosyltransferase
E. Adenosine deaminase

19. A 6-month old boy becomes progressively lethargic and pale and shows delayed motor
development. Lab work reveals normal urea levels and decreased presence of leukocytes. A bone
marrow aspirate shows the presence of megaloblasts which didn’t respond to treatment with folic acid
or vitamin B12. A urine specimen indicates the presence of orotic acid crystals. The underlying defect
causing this child’s symptoms is most likely in which pathway?

A. Homocysteine metabolism
B. Pyrimidine synthesis
C. Urea synthesis
D. Uric acid synthesis
E. Heme synthesis
20. PRPP appears in the biosynthesis of purine and pyrimidine nucleotides. What role does the
pyrophosphate play?

A. Subsequent hydrolysis of the pyrophosphate group provides significant free energy which favors
nucleotide synthesis
B. It activates the C-1’ carbon on ribose for substitution by either a purine or pyrimidine base
C. It forms a bridge between the terminal phosphate and either a purine or pyrimidine base
D. It activates the C-5’ carbon for substitution by either a purine or pyrimidine base
E. It undergoes an oxidation reaction to give a lactone intermediate which is coupled to either a
purine or pyrimidine base

21. A 31-year old male presents to his physician with a “tight sensation” in his calves and thighs, which
is aggravated by exertion. Examination of muscle function reveals normal nerve conduction but a biopsy
of the gastrocnemius muscle shows small crystals are within the muscle. Blood and urinalysis are normal
except for unusually low uric acid levels. Further investigation reveals hypoxanthineuria and xanthinuria.
Which enzyme is most likely defective in this patient?

A. Adenosine deaminase
B. Adenosine phosphoribosyltransferase
C. Guanine deaminase
D. PRPP synthetase
E. Xanthine oxidase

22. Inosine monophosphate can be used for the production of which of the following molecules?

A. CMP
B. UTP
C. AMP
D. Xanthine monophosphate
E. OMP

23. A 56-year old female has been diagnosed with bladder cancer and is being treated with 5-FU. 5-FU is
successful in destroying the tumor cells because it blocks production of which one of the following?

A. THF
B. UMP
C. Methylcobalamin
D. dTMP
E. CTP
 Answers
1) A – Alanine can be directly converted to pyruvate via transamination. The other amino acids may
produce glucogenic fragments which are eventually converted to pyruvate, but the question asks for
“direct” conversion. The single step for Ala is much more direct than the several steps the others may
require.

2) E – HMG CoA synthase will be active because excess acetyl CoA will be converted into fatty
acids/triacylglycerides. Glucokinase will not be active since there has been no ingestion of carbons. The
other enzymes are allosterically modulated (negatively) by NADH and/or ATP (generated by the NADH
from ethanol metabolism).

3) B – citrulline because hyperammonemia indicates the urea cycle is not functioning properly. The
accumulation of orotic acid is due to the accumulation of unreacted carbamoyl phosphate due to
defective ornithine transcarbamoylase. This is an in-born error (hence the protein restricted diet) and is
sex-linked as well (more prevalent in males since they only get 1 copy of the gene on the X-
chromosome). The question asks what is NOT being produced, and that is citrulline.

4) C – the MEOS can add extra capacity to convert ethanol to acetaldehyde in the cytosol, but no matter
how much acetaldehyde accumulates, it must be acted on by ADH in the mitochondria (and thus
becomes the bottleneck) to form acetate. So ADH is what limits etoh metabolism and enforces the
zeroeth order kinetics seen.

5) A – see slide 4 of the special products lecture

6) C – these are symptoms of Hartnup disease and this is confirmed by the high level of “multiple” amino
acids in the urine (cytinuria is mainly Cys). Niacin supplementation is part of the standard treatment
because Trp is lost due to the defective transporter and thus the body cannot make as much NAD+ on its
own. (The symptoms indicated as also consistent with niacin deficiency since they are due to lack of
NAD+)

7) A – Tagamet is metabolized by CYP2E1 – the same one in the MEOS (and located in the same place).
Since there is more etoh present it is being metabolized first and unmetabolized Tagamet is backing up
in the body – causing the symptoms seen.

8) D – -ketoglutarate because ALL aminotransferases remove the amine group from the amino acid
and transfer it to -ketoglutarate to make Glu. See the 1st general amino acid reaction in the urea
cycle/reactions of AA lecture.

9) A – Glu can undergo oxidative deamination (via glutamate dehdydrogenase) to yield -ketoglutarate,
an intermediate of the TCA. Or Glu can swap its amine group to pyruvate to make Ala (via alanine
aminotransferase) to yield -ketoglutarate. The former reaction is favored when cellular ADP or AMP
levels are elevated and the -ketoglutarate produced generates NADH and FADH2 for ATP production.

10) A – pepsin is an endopeptidase so there should be some fragmentation of the protein, but residence
time in the stomach is short and not much digestion can occur. Hence the limited digestion seen in the
lab results. Even though enteropeptidase is present, trypsin is not being activated. This means the other
enzymes listed are not being activated as well since they all depend on trypsin to be converted from the
zymogen to active form. Also, pepsin is secreted by the stomach and activated by H+ but the others are
secreted by the pancreas so pepsin’s distinct source makes it less likely to be affected by whatever is
altering the secretion/activity of the other enzymes.

11) B – Asn is derived from Asp and the amine group for the side chain is donated by Gln.

12) D – His is the only one listed that requires folate (see slide 19 of the amino acid metabolism lecture
and learning objective about which vitamins are needed for metabolism of which AA). Met requires Vit
B6 or Vit B12 to avoid homocysteine buildup.

13) D – The NADH provides and tetrahydrobiopterin and added to see if Phe can pass through the first
step of its metabolism to Tyr. The -ketoglutarate is added to facilitate the deamination of Tyr (via
transamination to form Glu) which produces p-hydroxyphenylpyruvate. The fact that p-
hydroxyphenylpyruvate is formed rules out Tyrosinema II. The lack of homogentisate and accumulation
of p-hydroxypheylpyruvate indicates metabolism has stopped and that p-hydroxyphenylpyruvate
deoxygenase is defective/not being produced and so the condition is tyrosinemia III (see AA metab self
study slides 13-14).

14) E – NAD+ (derived from Niacin) is required for the branched chain -keto dehydrogenase complex to
function properly (see AA metabolism slide 30). The other AA listed all require vitamin B6 for their
respective aminotransferases to work, and His required folic acid, but none utilize NAD+ as part of their
metabolism.

15) A – See slide 30 of the etoh metabolism lecture. NADH acts on -ketoglutarate dehydrogenase but
ATP (as listed in answer D) does not (succinyl CoA does).

16) D – IMP is the initial nucleotide product of purine biosynthesis and when present in elevated levels
will turn off glutamine PRPP amidotransferase. A and B are incorrect because neither of these molecules
are involved in regulating purine biosynthesis. C is incorrect because while glutamine is needed for de
novo purine biosynthesis it does not regulate any of the steps in the pathway. E is incorrect because
decreases in PRPP levels would result in decreased purine biosynthesis.

17) C – you are told that 6-mercaptopurine is deactivated by xanthine oxidase (XO) but we know that
allopurinol binds to XO inhibiting its activity therefor the drug won’t be deactivated and it will be
effective longer. A is incorrect because XO’s activity will be decreased with allopurinol administration so
there would be decreased deactivation of 6-mercaptopurine. B is incorrect because XO won’t be able to
inactivate the drug for elimination. D is incorrect because glutamine PRPP amidotransferase is part of
purine biosynthesis and does not interact with XO.

18) B – base/nucleotide analogs that are used to treat cancer do so by impairing DNA synthesis at some
level. In a non-resistant cancer cell, HGPRT could be used to salvage 6-mercaptopurine causing problems
with DNA synthesis. By losing HGPRT activity, resistant cells would be unaffected by 6-mercaptopurine.
A and D are incorrect because these enzymes are involved in pyrimidine nucleotide synthesis and
wouldn’t be impacted by this drug. C and E are incorrect because they are involved in the degradation of
purines.

19) B – this individual has a defect in UMP synthase activity which is leading to the build-up of orotic
acid. A is incorrect because if there were a problem with homocysteine conversion to methionine
treatment with vitamin B12 would have likely corrected that problem. C is incorrect because you are told
that the individual has normal urea levels therefore the defect is not in CPS I. D is incorrect because uric
acid is produced by metabolism of purine nucleotides. E is incorrect because orotic acid isn’t part of
heme metabolism.

20) A –hydrolysis of pyrophosphate by pyrophosphatase has a negative G making the production of

nucleotides and energetically favorable process. B is incorrect because the purine ring is assembled onto
PRPP unlike the pyrimidine base which could be thought of as substitution. D is incorrect because the
pyrophosphate is on the 1’ position. C and E are made up.

21) E – hypoxanthine and xanthine are degradation products of purine nucleotides. They are converted
to uric acid by xanthine oxidase. A defect in this enzyme would account for the elevated levels of these
bases. D is incorrect because this enzyme is involved in nucleotide synthesis. A and C are incorrect
because those enzymes are further up in the degradative pathway and wouldn’t contribute to elevated
hypoxanthine and xanthine. B is incorrect because that is the enzyme used to salvage adenosine so
there would be fewer purine nucleotides to degrade.

22) C – IMP is the initial nucleotide product in de novo purine nucleotide synthesis and can be used to
produce either AMP or GMP. A, B and E are incorrect because they are pyrimidines nucleotides and
produced by different mechanisms. D is incorrect because the correct intermediate is xanthosine
monophosphate. Xanthine is the free base and it is not phosphorylated.

23) D – 5-fluorouracil is a nucleotide analog that binds irreversibly to thymidylate synthase inhibiting the
activity of this enzyme there by preventing the production of dTMP. See slide 14 in the pyrimidine
lecture. The remaining answers are all incorrect because thymidylate synthase has no role in the
production of any of these compounds.