Deck 32: Nitrogen: Nucleotide Metabolism

Question 1

You are treating a 4-year-old child who has been afflicted with recurrent infections. The child exhibits retarded development, weakness, and weight loss. Physical examination also shows absent tonsils and blood work reveals a lack of lymphocytes. These signs and symptoms are due to which of the following disorders?

A) hyperuricemia
B) Kelley-Seegmiller syndrome
C) Lesch-Nyhan syndrome
D) orotic aciduria
E) severe-combined immunodeficiency (SCID)

Answer 1

severe-combined immunodeficiency (SCID)

Question 2

You are examining a 7-year-old male child who exhibits delayed motor development, overexaggerated reflexes, and spasticity. In addition, the boy has a tendency to chew his lips and fingers often causing tissue damage and bleeding and has painful, swollen, and inflamed joints. The most likely diagnosis in this case is Lesch-Nyhan syndrome. Analysis of blood from this patient would be expected to find elevated levels of which of the following compounds related to the observed findings?

A) citrulline
B) hypoxanthine
C) lactic acid
D) orotic acid
E) uric acid

Answer 2

uric acid

Question 3

You are examining a 5-year-old male child who has been exhibiting a tendency to bite his lower lip to the point of bleeding as well as chewing on his fingertips. Physical examination demonstrates swollen tender joints, and blood workup indicates elevated uric acid levels. These symptoms and lab results are indicative of a deficiency in which of the following enzymes?

A) adenosine deaminase
B) adenosine phosphoribosyltransferase
C) AMP deaminase
D) hypoxanthine-guanine phosphoribosyltransferase
E) thymidylate synthase

Answer 3

hypoxanthine-guanine phosphoribosyltransferase

Question 4

Allopurinol is an inhibitor of xanthine oxidase. Administration of allopurinol to a patient with gout and normal HGPRT levels would be expected to lead to which of the following?

A) decreased levels of PRPP
B) decreased xanthine in the blood
C) increased de novo synthesis of IMP
D) increased hypoxanthine in the urine
E) increased urate in the urine

Question 5

Thioredoxin is involved in which of the following reactions?

A) conversion of a ribonucleotide to a deoxyribonucleotide
B) conversion of AMP to ATP
C) conversion of dUMP to dTMP
D) degradation of nucleoproteins
E) inhibition of xanthine oxidase as a treatment for gout

Question 6

An enzyme system, isolated from the liver, converts deoxyuridine-5′-phosphate (dUMP) to thymidine-5′-phosphate (dTMP). Which of the following participates in this reaction?

A) ATP
B) N₅,N₁₀-methylene tetrahydrofolic acid
C) S-adenosylmethionine
D) thioredoxin
E) vitamin B₁₂

Question 7

5-Fluorouracil is utilized as a chemotherapeutic agent because of its ability to interfere with the function of which of the following enzymes?

A) dihydrobiopterin reductase
B) dihydrofolate reductase
C) dihydropyrimidine dehydrogenase
D) glycine synthase
E) thymidylate synthase

Question 8

Methotrexate is an inhibitor of which of the following enzymes?

A) dihydrofolate reductase
B) 5-methyl-tetrahydrofolate transferase
C) ribonucleotide reductase
D) thymidylate synthase
E) xanthine oxidase

Question 9

The parents of a 1-year-old boy are alarmed at the increasing frequency of their child biting his lips and finger tips. In addition, on several occasions they have noticed what appears to be "orange sand" in their son's diapers. They report to their pediatrician that they believe their child is delayed in acquiring motor skills such as holding up his head and sitting unaided. Clinical tests performed on serum and urine indicate a 3-fold increase in serum uric acid and a 10-fold elevation in the urinary ratio of uric acid to creatinine. These findings are suggestive of which of the following disorders?

A) adenosine deaminase deficiency
B) adenylosuccinate lyase deficiency
C) Lesch-Nyhan disease
D) purine nucleotide phosphorylase deficiency
E) orotic aciduria

Question 10

A 37-year-old man presents with tophaceous deposits within the articular cartilage, synovium, tendons, tendon sheaths, pinnae, and the soft tissue on the extensor surface of the forearms. These clinical observations suggest the patient is suffering from which of the following disorders?

A) ADA deficiency
B) gout
C) Lesch-Nyhan syndrome
D) purine nucleoside phosphorylase (PNP) deficiency
E) von Gierke disease

Question 11

The initial reaction of the de novo synthesis pathway for pyrimidine nucleotides begins with glutamine and CO₂ and is complete with the formation of uridine monophosphate. Which of the following represents the rate-limiting enzyme in this pathway?

A) aspartate transcarbamoylase
B) orotate monophosphate decarboxylase
C) phosphoribosylpyrophosphate amido transferase
D) PRPP synthetase
E) ribonucleotide reductase

Question 12

Severe combined immunodeficiency disease (SCID) is characterized by a complete lack of cellmediated and humoral immunity. This disorder results from a deficiency in which of the following enzymes?

A) adenosine deaminase
B) asparatate transcarbamoylase
C) hypoxanthine-guanine phosphoribosyltransferase
D) orotic acid decarboxylase
E) purine nucleotide phosphorylase

Question 13

Following a relatively normal early developmental period, a 6-month-old boy becomes pale and lethargic and begins to show signs of deteriorating motor skill. The infant has severe megaloblastic anemia; however, serum measurements of iron, folate, vitamins B₁₂, and B₆ demonstrate they are within normal range. Urine samples were clear when fresh, but when left to stand for several hours showed an abundant white precipitate that was composed of fine needle-shaped crystals. Analysis of the crystals identified them as orotic acid. Significant clinical improvement would be expected to be observed in this infant following oral administration of which of the following compounds?

A) adenosine
B) cytidine
C) guanosine
D) thymidine
E) uridine

Question 14

You are attending to a patient who manifests with orotic aciduria. You suspect a defect in pyrimidine nucleotide biosynthesis, but aside from the orotic aciduria there are no other classical symptoms apparent in this patient, such as megaloblastic anemia, and the activity of UMP synthetase is normal. Which of the following enzymes is most likely deficient in this patient leading to the orotic aciduria?

A) aspartate transcarbamoylase
B) ornithine transcarbamoylase
C) thymidine synthase
D) orotate phosphoribosyltransferase
E) orotidine-5′-phosphate carboxylase

Question 15

A nucleoside analogue that is being screened as a potential anticancer agent causes gout in clinical trials. Which of the following actions of this drug may cause gout?

A) inhibits carbamoyl phosphate synthetase
B) inhibits the conversion of dihydrofolate to tetrahydrofolate
C) inhibits xanthine oxidase
D) interferes with feedback control of phosphoribosylpyrophosphate (PRPP) synthesis
E) interferes with feedback control of thymidylate synthase

Question 16

Which of the following groups of amino acids are nitrogen donors in purine ring biosynthesis?

A) arginine, lysine, histidine
B) asparagine, lysine, histidine
C) glutamate, histidine, aspartate
D) glutamine, glycine, aspartate
E) glycine, proline, lysine

Question 17

Ribose-5-phosphate is activated for participation in nucleotide biosynthesis by conversion to which of the following derivatives?

A) ADP ribose
B) CDP ribose
C) GDP ribose
D) UDP ribose
E) 5-phosphoribosyl-1-pyrophosphate

Question 18

In the synthesis of pyrimidines, which of the following molecules is a direct precursor of the pyrimidine ring?

A) aspartate
B) fumarate
C) glutamate
D) glycine
E) 5-phosphoribosyl-1-pyrophosphate

Question 19

A 30-year-old man comes to the ER because he has had constant severe pain in his right ankle over the past 24 hours. His uncle also had episodes of pain in single joints. The ankle is swollen and warm. Serum uric acid concentration is increased. Which of the following enzyme activities is most likely to be decreased in this patient?

A) adenosine deaminase
B) carbamoyl phosphate synthetase
C) hypoxanthine guanine phosphoribosyltransferase
D) ribonucleotide reductase
E) thymidylate synthase

Question 20

A 10-year-old boy who has begun chemotherapy for acute myelogenous leukemia awakens at night with fever and severe pain in the ankles. Treatment with over-the-counter analgesics does not resolve the pain. The next morning, he has pain with urination and blood in the urine. Increased degradation of which of the following compounds most likely caused this patient's symptoms?

A) amino acids
B) fatty acids
C) purines
D) pyrimidines
E) vitamin C

Question 21

A 6-year-old boy with moderate mental retardation is brought to the physician for a follow-up examination. He has had choreoathetoid movements since the age of 16 months. He has been biting his lips and fingers for the past 2 months. His older brother has a similar condition. Physical examination shows spasticity of the lower limbs. Laboratory studies show an increased serum uric acid concentration and an increased urinary excretion of uric acid. His increased serum uric acid concentration is most likely due to which of the following?

A) deficient amidophosphoribosyltransferase activity
B) deficient hypoxanthine guanine phosphoribosyltransferase activity
C) deficient xanthine oxidase activity
D) increased adenosine phosphoribosyltransferase activity
E) increased adenosine deaminase activity

Question 22

The gouty arthritis in patients with Lesch-Nyhan syndrome results from a genetic defect in which of the following enzymes?

A) adenosine phosphoribosyltransferase
B) glutathione reductase
C) hypoxanthine guanine phosphoribosyltransferase
D) phosphoribosylpyrophosphate amidotransferase
E) xanthine oxidase

Question 23

A 7-year-old boy is brought to the physician by his mother for a follow-up examination. He has had choreoathetosis, spasticity, and mental retardation since infancy and self-mutilation for 3 years. Laboratory studies show an increased serum uric acid concentration. The enzyme deficiency causing this disorder increases serum uric acid concentration by which of the following changes in purine metabolism?

A) decreased activity of xanthine oxidase
B) decreased formation of adenosine monophosphate
C) decreased utilization of phosphoribosylpyrophosphate (PRPP) in salvage
D) increased activity of adenosine deaminase
E) increased activity of PRPP synthetase

Question 24

A 63-year-old woman comes to the physician for a follow-up examination. She has metastatic breast cancer treated with cyclophosphamide and fluorouracil. Thymidylate synthase, which is required for deoxynucleotide synthesis, is one target of fluorouracil. Which of the following is a substrate for thymidylate synthase?

A) dCMP
B) dCTP
C) dUDP
D) dUMP
E) dUTP

Question 25

A 4-month-old boy is brought to the physician because of failure to thrive since birth. He is below the 5th percentile for length and at the 100th percentile for weight. Physical examination shows a doll-like face and marked hepatomegaly. After a 4-hour fast, serum studies show a decreased glucose concentration and increased concentrations of lactate, triglycerides, and uric acid. Which of the following is the most likely mechanism for the increased serum uric acid concentration in this patient?

A) decreased hepatic amidophosphoribosyltransferase activity
B) decreased hepatic hypoxanthine-guanine phosphoribosyltransferase activity
C) decreased hepatic phosphoribosylpyrophosphate activity
D) increased degradation of hepatic purine nucleotides
E) increased degradation of hepatic pyrimidine nucleotides

Question 26

A 3-year-old boy develops renal failure from hyperuricemia on the second day of cytosine arabinoside therapy for acute myelogenous leukemia. Which of the following is the most likely cause of his hyperuricemia?

A) increased catabolism of purines that are released from lysed leukemic cells
B) inhibition of orotic acid production via the urea cycle
C) inhibition of renal tubular transport by cytosine arabinoside
D) inhibition of uric acid for renal excretion by ketone bodies
E) overproduction of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) by the leukemic cells