Deck 18: Nucleotide Metabolism

Question 1

Which of the following is synthesized by a complex that requires an electrochemical gradient to function?

A) ATP
B) cAMP
C) GTP
D) ribose

Answer 1

ATP

Question 2

Which of the following is NOT a general role of nucleotides in cells?

A) energy conversion reactions
B) signal transduction pathways
C) genetic information storage
D) proteolysis

Answer 2

proteolysis

Question 3

The nitrogen atoms of a purine originate from all of the following amino acids EXCEPT

A) glycine.
B) aspartate.
C) cysteine.
D) glutamine.

Answer 3

cysteine.

Question 4

Which nitrogen originates from aspartate?

A) A
B) B
C) C
D) D

Question 5

Which of the following is a coenzyme that is derived from ATP?

A) coenzyme Q
B) FAD
C) heme
D) Fe₄-S₄ cluster

Question 6

A mutation in the gene encoding which of the following enzymes would affect the synthesis of both AMP and GMP?

A) adenylosuccinate synthetase
B) PRPP synthetase
C) IMP dehydrogenase
D) GMP synthase

Question 7

Purine biosynthesis takes place in two stages. The first stage begins with ribose-5-phosphate and ends with

A) 5-phosphoriboxylamine.
B) 5-aminoimidazole ribonucleotide.
C) inosine-5 ^' -monophosphate.
D) 5-aminoimidazole-4-carboxamide ribonucleotide.

Question 8

Analysis of AMP and GMP synthesized in E. coli grown in medium containing ^{1 5}N-labeled aspartate would show that

A) AMP contained twice as much ^{1 5}N than GMP.
B) GMP contained twice as much ^{1 5}N than AMP.
C) AMP contained three times as much ^{1 5}N than GMP.
D) they contain the same levels of ^{1 5}N.

Question 9

In analyzing the intermediates formed during the conversion of IMP to GMP and AMP, which molecule would one expect to find in the conversion to GMP but NOT in the conversion to AMP?

A) xanthosine-5 ^' -monophosphate
B) adenylosuccinate
C) 5-phosphoriboxylamine
D) 5-aminoimidazole ribonucleotide

Question 10

To synthesize nucleotide monophosphates from oligonucleotides in a test tube, which enzyme must be included in the reaction mixture?

A) phosphodiesterases
B) nucleotidases
C) kinases
D) phosphopentomutase

Question 11

If HCO₃^- that is radioactively labeled with ¹³C is available, which carbon atom in the molecule below would ultimately be expected to be radioactive?

A) A
B) B
C) C
D) D

Question 12

In purines, __________ nitrogen atoms and __________ carbon atoms originate from glycine.

A) 0; 2
B) 1; 1
C) 2; 1
D) 1; 2

Question 13

The transformation of ribose-5-phosphate to AIR in the first stage of purine biosynthesis in E. coli consumes the equivalent of 5 ATP. The second stage consumes

A) an additional 5 ATP.
B) more than 5 ATP.
C) less than 5 ATP and generates 1 ATP.
D) less than 5 ATP.

Question 14

The conversion of ribose-1-phosphate to ATP via the salvage pathway would require the activity of several enzymes. Choose the answer that lists them in the order that they would act in this pathway.

A) PRPP synthetase; phosphopentomutase; kinase; kinase; phosphoriboxyl transferase
B) PRPP synthetase; phosphoriboxyl transferase; phosphopentomutase; kinase; kinase
C) phosphopentomutase; PRPP synthetase; phosphoriboxyl transferase; kinase; kinase
D) phosphopentomutase; phosphoriboxyl transferase; kinase; PRPP synthetase; kinase

Question 15

The molecule below is a precursor to the formation of which of the following second messengers?

A) ADP
B) cAMP
C) NAD⁺
D) PKA

Question 16

Analysis of enzyme activities in a cell in the absence and presence of AMP and GMP is completed. Which enzyme would show lower activity when AMP is added but not when GMP is added?

A) glutamine-PRPP aminotransferase
B) adenylosuccinate synthase
C) IMP dehydrogenase
D) PRPP synthetase

Question 17

The carbon atoms of a purine originate from glycine and

A) "^N10-formyl-THF."
B) "aspartate."
C) "glycinamide."
D) "glutamate."

Question 18

A person wishes to determine the role of PRPP synthetase in a newly discovered organism. He or she decides that a good way to do this would be to see what happens when PRPP synthetase is inhibited. Which of the following could be added to a cell from this organism to inhibit PRPP synthetase?

A) GDP
B) AMP
C) ATP
D) GTP

Question 19

A product of the first stage of purine biosynthesis is , whereas is a by-product of the second stage.

A) fumarate; glycine
B) glutamine; glutamate
C) fumarate; glutamate
D) glutamate; fumarate

Question 20

Which of the following is a benefit of nucleotide salvage pathways compared with de novo synthesis?

A) increased variety of nucleotides produced
B) increased half-life of mRNA
C) reduced energy expenditure
D) decreased regulation of nucleotide homeostasis

Question 21

Aspartate contains four carbons. If all are radioactively labeled, how many carbons of UMP will be radioactively labeled?

A) 0
B) 2
C) 3
D) 4

Question 22

Which of the following is an intermediate in the conversion of AMP to uric acid but NOT an intermediate in the conversion of GMP to uric acid?

A) A
B) B
C) C
D) D

Question 23

The possibility of ADA-SCID is indicated by than normal activity of .

A) lower; ribonucleotide reductase
B) higher; adenosine deaminase
C) lower; HGPRT
D) higher; xanthine oxidase

Question 24

During the biosynthesis of UMP from carbamoyl phosphate and aspartate, dihydroorotate is converted to which of the following compounds?

A) carbamoyl aspartate
B) orotate
C) orotidine-5 ^' -monophosphate
D) quinone

Question 25

A person is carrying out in vitro synthesis of uric acid from GMP. He or she wants to include all substrates and enzymes necessary. All EXCEPT should be included in the reaction mixture.

A) adenosine deaminase
B) purine nucleoside phosphorylase
C) guanine deaminase
D) xanthine oxidase

Question 26

If GMP radiolabeled at the nitrogen atom indicated by the * were metabolized to uric acid, which of the following molecules along the pathway would also be radioactive?

A) uric acid
B) guanine
C) NH₄⁺
D) xanthine

Question 27

Uric acid is processed to allantoic acid, which is then secreted. In which of the following organisms does this occur?

A) insects
B) bony fish
C) marine invertebrates
D) amphibians

Question 28

Samples from a bird, reptile, amphibian, and primate were analyzed by Western blotting for the expression of allantoinase, the enzyme that converts allantoin to allantoic acid. Unfortunately the researcher forgot the order that the samples were loaded into the gel. Luckily, only a single sample indicated allantoinase. Which sample contained allantoinase?

A) bird
B) reptile
C) amphibian
D) primate

Question 29

How many of the nitrogens in orotidine-5 ^' -monophosphate arise from glutamine?

A) 0
B) 1
C) 2
D) 3

Question 30

Marine invertebrates express enzymes that allow for the conversion of uric acid to NH₄⁺. What is the correct order of the action of enzymes in this pathway? 1. Urate oxidase
2) Allantoicase
3) Urease

A) 2; 3; 4; 1
B) 1; 2; 4; 3
C) 3; 4; 2; 1
D) 1; 4; 2; 3

Question 31

The conversion of adenosine to inosine is catalyzed by , which is deficient in .

A) HGPRT; Lesch-Nyhan syndrome
B) adenosine deaminase; ADA-SCID
C) xanthine oxidase; Lesch-Nyhan syndrome
D) purine nucleoside phosphorylase; ADA-SCID

Question 32

What enzymatic activity is NOT required during the biosynthesis of UMP from carbamoyl phosphate and aspartate?

A) dehydrogenase
B) decarboxylase
C) phosphoribosyl transferase
D) synthetase

Question 33

The conversion of hypoxanthine to IMP is catalyzed by , which is deficient in .

A) HGPRT; Lesch-Nyhan syndrome
B) adenosine deaminase; ADA-SCID
C) xanthine oxidase; Lesch-Nyhan syndrome
D) purine nucleoside phosphorylase; ADA-SCID

Question 34

An enzyme panel analysis of a patient reveals a lack of , which is an indication of Lesch-Nyhan syndrome.

A) PRPP synthetase
B) adenosine deaminase
C) HGPRT
D) xanthine oxidase

Question 35

Which of the following is the precursor of the indicated carbon atom in a pyrimidine ring?

A) aspartate
B) glycine
C) carbamoyl phosphate
D) orotate

Question 36

Place the steps converting GMP to uric acid in the correct order.
A. Conversion to guanine
B. Conversion to guanosine
C. Conversion to xanthine
D. Conversion to uric acid

A) A; C; B; D
B) A; B; C; D
C) B; C; A; D
D) B; A; C; D

Question 37

Which of the following organisms would generate this compound?

A) nonprimate mammals
B) birds
C) cartilaginous fish
D) primates

Question 38

If a mutation of the decarboxylase enzyme that functions in the biosynthetic pathway of UMP caused the pathway to halt at that step, which of the following would no longer occur?

A) reduction of a quinone
B) production of orotidine-5 ^' -monophosphate
C) generation of CO₂
D) generation of glutamate

Question 39

A nitrogen of a pyrimidine ring arises from which amino acid?

A) aspartate
B) asparagine
C) glycine
D) alanine

Question 40

Nonprimate mammals convert uric acid to allantoin. This reaction, catalyzed by urate oxidase, also generates which of the following products?

A) H₂O
B) H₂O₂
C) O₂
D) NH₄⁺

Question 41

Order the following steps involving the regeneration of ribonucleotide reductase that occurs in most animals so that it may carry out the formation of deoxyribonucleotides. (Note that not all steps are shown.) 1. Reduction of thioredoxin
2) Reduction of ribonucleotide reductase
3) Oxidation of thioredoxin reductase
4) Reduction of thioredoxin reductase

A) 3; 4; 1; 2
B) 2; 1; 3; 4
C) 4; 1; 2; 3
D) 4; 3; 1; 2

Question 42

Which answer INCORRECTLY pairs a substrate and subsequent product of dihydropyrimidine dehydrogenase?

A) thymine; dihydrothymine
B) uracil; dihydrouracil
C) adenine; dihydroadenine
D) 5-fluorouracil; fluorodihydrouracil

Question 43

To purify glutathione reductase to carry out a kinetics analysis, which organism would be the best source of the enzyme?

A) cod fish
B) chimpanzee
C) E. coli
D) turtle

Question 44

Complete the following pathway of the degradation of UMP. UMP $\rightarrow$ Uridine $\rightarrow$ __________ $\rightarrow$ Dihydrouracil $\rightarrow$ NH₄⁺ + HCO₃- +
$\beta$ -alanine

A) uracil; N-carbamoyl- $\beta$ -aminoisobutyrate
B) N-carbamoyl-uracil; $\beta$ -alanine CoA
C) uracil; N-carbamoyl- $\beta$ -alanine
D) orotate; uracil

Question 45

Consider a cell that is provided aspartate in which all carbons are radioactively labeled. Compounds in the cell are analyzed after the biosynthesis and subsequent breakdown of pyrimidines. Which of the following compounds would display no radioactivity signal during the analysis?

A) " $\beta$ -alanine"
B) "glutamine"
C) " $\beta$ -aminoisobutyrate"
D) "dihydrouracil"

Question 46

CTP synthetase is inhibited by __________ and activated by _.

A) CTP; GTP
B) CTP; UMP
C) ATP; GTP
D) GTP; UMP

Question 47

The chemotherapy agent 5-fluorouracil is usually degraded by which of the following enzymes, which requires administration of higher doses?

A) " $\beta$ -ureidopropionase"
B) "thymidine phosphorylase"
C) "dihydropyrimidine dehydrogenase"
D) "dihydropyrimidinase"

Question 48

$\beta$ -aminoisobutyrate is a breakdown product of

A) dATP.
B) dUMP.
C) dCMP.
D) dTMP.

Question 49

How many ATP are converted to ADP during the biosynthesis of CTP from UMP?

A) 0
B) 1
C) 2
D) 3

Question 50

What is the name of the compound below, which is an intermediate in the breakdown of some pyrimidines?

A) "N-carbamoyl- $\beta$ -alanine"
B) "N-carbamoyl- $\beta$ -aminoisobutyrate"
C) "dihydrothymine"
D) " $\beta$ -aminoisobutyrate"

Question 51

Dihydropyrimidine dehydrogenase deficiencies exist in approximately of humans and can result in complications when 5-fluorouracil is administered as a therapy.

A) 15%; cancer
B) 5%; cancer
C) 15%; autoimmunity
D) 5%; autoimmunity

Question 52

An oncologist has a patient with dihydropyrimidine dehydrogenase deficiency. Which of the following is a chemotherapy agent that the doctor should be cautious about using with this patient because of serious side effects?

A) "primaquine"
B) " $\beta$ -alanine"
C) "5-dihydrothymine"
D) "5-fluorouracil"

Question 53

Dihydropyrimidine dehydrogenase deficiencies can lead to an intolerance of high doses of 5-fluorouracil because 5-fluorouracil dihydropyrimidine dehydrogenase.

A) is usually metabolized by
B) inhibits
C) allosterically activates
D) denatures

Question 54

Consider the breakdown of the four compounds below. Which would be expected to generate $\beta$ -alanine?

A) dATP
B) dGMP
C) dCMP
D) dTMP

Question 55

To determine the role of glutaredoxin in the generation of deoxyribonucleotides by ribonucleotide reductase, which organisms would be the best to study?

A) bony fish
B) bacteria
C) humans
D) amphibians

Question 56

The biosynthesis of CTP is allosterically regulated at many steps. Which of the following is a major point of regulation?

A) dihydroorotate dehydrogenase
B) UMP kinase
C) nucleoside diphosphate kinase
D) UMP synthase

Question 57

How many PRPP are required to synthesize two UMP and two CTP from carbamoyl aspartate?

A) 0
B) 2
C) 4
D) 8

Question 58

Tyr122 is important in the mechanism of the E. coli ribonucleotide reductase. The function of this amino acid in the mechanism is to

A) carry out a nucleophilic attack on the substrate.
B) coordinate water in the active site.
C) generate the Cys439 radical species.
D) hydrogen-bond to the phosphates of the substrate.

Question 59

A mutation in may alter the rate at which UT is converted to CTP.

A) CTP synthetase
B) UTP dehydrogenase
C) CTP transferase
D) UTP decarboxylase

Question 60

The biosynthesis of deoxynucleosides is important, yet different organisms require different sets of enzymes to carry it out. If 100 different species were analyzed, which enzyme is most likely to be found in all of them?

A) ribonucleotide reductase
B) thioredoxin
C) glutaredoxin
D) glutathione reductase

Question 61

Which enzyme activity would be directly inhibited by the addition of methotrexate?

A) thymidine kinase
B) thymidylate synthase
C) dihydrofolate reductase
D) serine hydroxymethyltransferase

Question 62

Relate the broad substrate specificity of nucleoside diphosphate kinase to its role in the consumption and synthesis of nucleoside triphosphates.

Question 63

In severe combined immunodeficiency disease (SCID), ribonucleotide reductase activity is __________ because of an overabundance of _.

A) activated; dATP
B) activated; cAMP
C) inhibited; dATP
D) inhibited; cAMP

Question 64

Explain how a general inhibitor of endonucleases would alter the homeostasis of mRNA and affect the nucleotide salvage pathway.

Question 65

If an alteration occurred in the activity site of the R1 subunit of E. coli ribonucleotide reductase that allowed dATP to bind but precluded ATP binding to the site, a possible result would be that ribonucleotide reductase

A) would remain active under all conditions.
B) would be decreased when dATP bound both the activity and specificity sites.
C) activity would be increased when ATP bound the specificity site.
D) activity would be decreased when dCDP bound the catalytic site.

Question 66

Reduction in dTMP biosynthesis is NOT dependent upon _.

A) methotrexate
B) aminopterin
C) raltitrexed
D) dihydrofolate

Question 67

Contrast the energy required to drive the synthesis of AMP from IMP with that required to drive the synthesis of GMP from IMP.

Question 68

The importance of stable free radicals in the mechanism of E. coli ribonucleotide reductase was identified in the early 1970s. The existence of stable radicals in a protein had not been previously observed. Which of the following amino acids can exist as a stable radical in ribonucleotide reductase?

A) Cys
B) His
C) Ser
D) Glu

Question 69

An E. coli strain that is unable to synthesize purines because of a mutation in the gene encoding the AIR synthetase is transfected with the human gene coding for hTrifGART. Would this strain would be able to undergo mitosis in purine-depleted media? Explain your answer.

Question 70

The enzymes required to convert PRPP to IMP in animal cells form a large protein complex called a(n) _. Describe the experimental evidence proving the existence of this
complex.

Question 71

When analyzing the production of dTMP by thymidylate synthase in a cell-free system, which of the following compounds would be found as an additional product of this enzyme?

A) 7,8-dihydrofolate
B) NADP⁺
C) N⁵,N^{1 0}-methylenetetrahydrofolate
D) glycine

Question 72

Contrast the binding of nucleotides to the activity site and specificity site on the R1 subunit of E. coli ribonucleotide reductase by choosing the nucleotide that can bind to the specificity site but NOT the activity site.

A) ATP
B) dTTP
C) dATP
D) dCDP

Question 73

Which enzyme activity would be directly reduced if fluorodeoxyuridine-5 ^' -monophosphate is present?

A) thymidine kinase
B) thymidylate synthase
C) dihydrofolate reductase
D) serine hydroxymethyltransferase

Question 74

Contrast the role of kinases and nucleotidases in the nucleotide salvage pathway.

Question 75

Place the following steps in their proper order starting with dUMP and N⁵,N^{1 0}-methylenetetrahydrofolate as substrates. 1. Formation of tetrahydrofolate
2) Formation of N⁵,N^{1 0}-methylenetetrahydrofolate
3) Formation of 7,8-dihydrofolate

A) 2; 1; 3
B) 1; 3; 2
C) 1; 2; 3
D) 3; 1; 2

Question 76

A compound is added to a cell and dihydrofolate reductase activity is reduced. If this compound is , it can be predicted that a similar result would be seen if were added instead.

A) methotrexate; aminopterin
B) methotrexate; raltitrexed
C) aminopterin; raltitrexed
D) aminopterin; fluorodeoxyuridine-5 ^' -monophosphate

Question 77

To study the allosteric regulation of E. coli ribonucleotide reductase in a cell-free in vitro system, which of the following would be a good choice to add to the system?

A) glucose
B) ATP
C) Ca²⁺
D) IP₃

Question 78

Describe how the levels of cAMP would change in a liver cell before and after exposure to glucagon. Compare these with the levels expected if the cell were previously exposed to an inhibitor of adenylate cyclase.

Question 79

Several cysteines play important roles in the mechanism of E. coli ribonucleotide reductase. Which is NOT a role carried out by cysteine in this enzyme?

A) donation of a hydrogen atom to the substrate
B) removal of a hydrogen atom from the substrate
C) donation of a proton to ultimately form water
D) reduction of thioredoxin

Question 80

Identify the carbon atom that is attacked by Cys439 in the first step of the E. coli ribonucleotide reductase mechanism.

A) A
B) B
C) C
D) D