Deck 26: Synthesis and Degradation of Nucleotides

Question 1

The fate of IMP is regulated by relative levels of ____ and ____; and energy to drive AMP synthesis is provided by ____, and energy for GMP synthesis by ____.

A) IMP; PRPP; ATP; GTP
B) PRPP; ATP; ATP; GTP
C) AMP; ATP; GTP; ATP
D) AMP; GMP; GTP; ATP
E) IMP; GMP; ATP; GTP

Answer 1

D

Question 2

Which of the following statements explains why allopurinol is able to prevent gout?

A) it binds to uric acid thus preventing the formation of uric acid crystals
B) it acts as a diuretic to increase the elimination of uric acid
C) it inhibits the production of uric acid and allows for the more highly soluble xanthine and hypoxanthine to be excreted from the body
D) it stimulates the purine salvage pathway, thus eliminating the need for production of uric acid
E) none of the above

Answer 2

C

Question 3

Many ____ and ____ are inhibitors of purine and pyrimidine biosynthesis.

A) eicosanoids; aspirin
B) NSAIDs; antibiotics
C) antibiotics; eicosanoids
D) anticancer drugs; antibiotics
E) anticancer drugs; eicosanoids

Answer 3

D

Question 4

Glutamine phosphoribosyl pyrophosphate amidotransferase catalyzes step 2 in the biosynthesis of purines. Which of the following is a true statement regarding the regulation of this enzyme?

A) It is accelerated by an input of ATP or GTP.
B) It is sensitive to activation by azaserine.
C) It is accelerated by an input of AMP or GMP.
D) The G series of nucleotides as well as the adenine nucleotides act as competitive inhibitors.
E) It is subject to feed-forward activation by ADP.

Question 5

All are substrates of carbamoyl phosphate synthetase II (CPS-II) EXCEPT:

A) H₂O.
B) NH₄⁺.
C) HCO₃−.
D) glutamine.
E) 2ATP.

Question 6

In purine biosynthesis when glycine adds to 5-phosphoribosyl-β-amine, the bond formed is a(n):

A) ester.
B) imine.
C) amine.
D) amide.
E) lactam.

Question 7

All are characteristics of xanthine oxidase EXCEPT:

A) present in large amounts in liver, intestinal mucosa and milk.
B) uses molecular oxygen and produces H₂O₂.
C) involved in production of urea.
D) possesses an electron-transport chain with FAD, Fe−S cluster and molybdenum cofactor.
E) all are true.

Question 8

What is the function of phosphoribosyltransferases?

A) they are involved in the reversible reactions of purine salvage.
B) they mediate the degradation of AMP.
C) they are central to the re-synthesis of nucleotides from bases in salvage reactions.
D) they mediate the degradation of IMP.
E) they are competitive inhibitors employed in the salvage of purine nucleotides.

Question 9

All are characteristics of Lesch-Nyhan Syndrome EXCEPT:

A) gouty arthritis due to excessive uric acid accumulation
B) severe malfunctions of the nervous system
C) complete deficiency in HGPRT activity
D) congenital, recessive, sex-linked trait manifested only in males
E) all are true

Question 10

The reaction, base + PRPP → nucleoside-5-phosphate + PP_i is catalyzed by the enzyme:

A) nucleotide diphosphate kinase.
B) phosphoribosyltransferase.
C) ribose-5-phosphate pyrophosphokinase.
D) adenylate kinase.
E) GMP synthetase.

Question 11

What is the common product of purine catabolism?

A) xanthine
B) uric acid
C) inosine
D) hypoxanthine
E) xanthosine

Question 12

All of the following statements about nucleotides are true EXCEPT:

A) They are produced by nearly all organisms.
B) The rate of proliferation of a cell can determine the amount of DNA and RNA synthesized per unit of time.
C) Uridine nucleotide derivatives of carbohydrates are common intermediates in cellular transformation of carbohydrates.
D) Many coenzymes are derivatives of nucleotides.
E) The nitrogenous bases serve as energy sources.

Question 13

All of the following are true concerning the regulation of the purine biosynthetic pathway EXCEPT:

A) ATP is the energy source for AMP synthesis.
B) ADP and GDP are feedback inhibitors of ribose-5-phosphate pyrophosphokinase.
C) "A" and "C" nucleotides allosterically inhibit glutamine phosphoribosyl pyrophosphate amidotransferase (Gln:PRPP amidotransferase).
D) The rate of IMP formation is dependent on the levels of the adenine and guanine nucleotides produced.
E) PRPP competitively inhibits the enzyme Gln:PRPP amidotransferase.

Question 14

About 30% of severe combined immunodeficiency syndrome (SCIDS) patients suffer from a deficiency in the activity of the enzyme ____ that is a ____-dependent enzyme and ____ deficiency can also lead to reduced immune function.

A) HGPRT; Ca²⁺; Ca²⁺
B) nucleosidase; Ca²⁺; Ca²⁺
C) nucleoside phosphorylase; P_i; P_i
D) adenosine deaminase; Zn²⁺; Zn²⁺
E) none are true

Question 15

What is the importance of the purine nucleoside cycle?

A) It participates in the conversion of purines into pyrimidines.
B) It generates fumarate, which inhibits the formation of AMP from IMP.
C) It provides fumarate as an anaplerotic enhancement of the citric acid cycle.
D) It inhibits the citric acid cycle in skeletal muscles.
E) It is used in energy metabolism in the liver.

Question 16

What is the limiting substance in the biosynthesis of purines?

A) ribose-5-phosphate
B) 5-phosphoribosyl-β amine
C) formylglycinamidine ribonucleotide
D) 5-phosphoribosyl-α-pyrophosphate (PRPP)
E) α-D-ribose-5-phosphate

Question 17

Adenylosuccinase (adenylosuccinate lyase) catalyzes the reaction to remove ____ after ____ has formed an amide with a carbonyl group in purine biosynthesis.

A) succinate; glutamate
B) succinate; aspartate
C) fumarate; alanine
D) fumarate; aspartate
E) α-ketoglutarate; glutamate

Question 18

The coenzyme for two single carbon additions in purine biosynthesis is:

A) THF.
B) biotin.
C) SAM.
D) TPP.
E) none are true.

Question 19

Allopurinol is an analog of ____ that tightly binds to ____ and prevents ____ formation.

A) hypoxanthine; xanthine oxidase; uric acid
B) guanine; guanine deaminase; xanthine
C) inosine; xanthine oxidase; xanthine
D) hypoxanthine; guanine deaminase; xanthine
E) none of the above

Question 20

Which of the following statements explains why methotrexate is effective as a cancer chemotherapeutic?

A) it serves as an analog of p-aminobenzoic acid and block bacterial synthesis of folate
B) acts as an inhibitor of dihydrofolate reductase, thus preventing production of tetrahydrofolate
C) it acts as a suicide substrates for the enzyme dihydropteroate synthetase
D) prevents the conversion of N⁵,N¹⁰-methenyl THF to N¹⁰-formyl THF which is required in 2 steps of the purine synthesis pathway
E) both b and d are correct

Question 21

Which of the following is a true statement regarding pyrimidine biosynthesis in animals?

A) PRPP and ATP are allosteric inhibitors.
B) CTP is a feedback inhibitor.
C) It is allosterically regulated at aspartate transcarbomoylase.
D) UDP and UTP are feedback inhibitors of CPS-II.
E) ACTase catalyzes the committed step in pyrimidine synthesis.

Question 22

Which of the following statements regarding the activity of ribonucleotide reductase is correct?

A) the overall activity of the enzyme is inhibited by high levels of ATP
B) binding of ATP to the specificity site increases the use of GDP as a substrate
C) binding of dGTP to the specificity site increases the use of CDP as a substrate
D) binding of dTTP to the specificity site inhibits the use of UDP as a substrate
E) none of the above

Question 23

Which of the following is the mechanism of action of 5-fluorouracil?

A) competitive inhibitor of dihydrofolate reductase
B) suicide substrate for thymidylate synthase
C) competitive inhibitor of ribonucleotide reductase
D) non-competitive inhibitor of thioredoxin reductase
E) none of the above

Question 24

Which form of the folate coenzyme is directly involved in sythesis of the purine ring?

A) N⁵,N¹⁰-methenyl THF
B) N¹⁰-formyl THF
C) N⁵-formyl THF
D) tetrahydrofolate
E) dihydrofolate

Question 25

Thymidylate synthase synthesizes dTMP from ____ by ____ utilizing the coenzyme ____.

A) dCTP; carboxylation; biotin
B) dUMP; methylation; THF
C) dCMP; methylation; THF
D) dGMP; phosphorylation; ATP
E) dUMP; phosphorylation; ATP

Question 26

Which of the following would cause an increase in the conversion of IMP to GMP?

A) high levels of CMP
B) high levels of dTTP
C) high levels of UMP
D) high levels of AMP
E) none of the above

Question 27

Thymine nucleotides are not synthesized directly by cells but indirectly from other pyrimidine deoxyribonucleotides. All of the following statements regarding thymine nucleotide synthesis are true EXCEPT:

A) dUMP is the immediate precursor for dTMP.
B) The action of dUTPase allows dUTP to serve as a substrate in DNA synthesis.
C) Thymidylate synthase catalyzes the formation of dTMP from dUMP.
D) The methyl donor in the reaction of dTMP is N⁵, N¹⁰-methylene-THF.
E) THF is used as a cofactor.

Question 28

Which of the following is an advantage of metabolic channeling?

A) It allows the product of one reaction to be available for a reaction later in another pathway.
B) It allows the diffusion of substrates.
C) It allows the dilution of substrates.
D) It allows a more diverse interaction of substrates, intermediates, and enzymes.
E) It does not allow for substrate dilution into the milieu and for the accumulation of intermediates.

Question 29

Unlike hydrogen, which is often abstracted from substrates as H⁺, electronegative ____ cannot be readily eliminated as ____, thus enzyme inhibitors can be fashioned in which ____ replaces H at positions where catalysis involves H-removal as H⁺.

A) sodium; Na⁺; Na
B) potassium; K⁺; K
C) deuterium; D⁺; D
D) fluorine; F⁺; F
E) all are true

Question 30

How do cells salvage purines?​

Question 31

Explain the regulation of pyrimidine biosynthesis in bacteria and animals.​

Question 32

The immediate reducing power of ribonucleotide reductase is provided by:

A) thioredoxin.
B) Ferredoxin.
C) NADH.
D) Fe−S complex.
E) Cyt P-450.

Question 33

What type of reaction gives UMP from OMP?

A) reduction
B) decarboxylation
C) oxidation
D) condensation
E) hydrolysis

Question 34

In mammals CPS-II is the regulated step on pyrimidine biosynthesis; however, in bacteria ____ is the regulated step.

A) dihydroorotase
B) aspartate transcarbamoylase (ATCase)
C) OMP decarboxylase
D) dehydroorotate dehydrogenase
E) none are true

Question 35

Discuss the regulation of the purine biosynthetic pathway after the formation of inosine monophosphate (IMP).​

Question 36

Which of the following serves as an activator of CPS-II in mammals?

A) thyrotropin
B) epidermal growth factor
C) cortisol
D) gonadotropin
E) none of the above

Question 37

Enzymatic ribonucleotide reduction is accomplished via a free radical mechanism. Which of the following statements is true regarding this process?

A) The substrate specificity site on the R1 homodimer determines if the enzyme is active or inactive.
B) R2 has a single active site containing two Fe atoms that generate the free radicals required for reduction.
C) R2, but not R1, function in the delivery of reducing equivalents.
D) R2 homodimer carries two regulatory sites.
E) A final decarboxylation forms the deoxyribonucleotide product.

Question 38

Which of the following serves as one of the nitrogen sources for the pyrimidine ring?

A) glutamate
B) carbamoyl phosphate
C) asparagine
D) glycine
E) none of the above

Question 39

​How are nucleotides degraded to uric acid?

Question 40

Which of the following is a source of 2 carbon atoms of the purine ring system?

A) aspartate
B) carbon dioxide
C) glycine
D) glutamine
E) glutamic acid

Question 41

​Discuss the role of thioredoxin in the synthesis of deoxynucleotides.