Deck 20: Purine and Pyrimidine Nucleotide Metabolism

Question 1

A reaction in human tissues which utilizes molecular oxygen directly is the

A) formation of uric acid.
B) production of creatinine.
C) conversion of ribose to deoxyribose.
D) formation of delta-aminolevulinic acid.
E) conversion of orotidine 5-phosphate to UMP.

Answer 1

formation of uric acid.

Question 2

Fluorouracil inhibits DNA synthesis by decreasing the cell's supply of dTMP through which of the following actions?

A) activation of uracil phosphoribosyltransferase
B) inhibition of thymidylate synthase
C) inhibition of ribonucleotide reductase
D) inhibition of thymidine kinase
E) activation of uridine phosphorylase

Answer 2

inhibition of thymidylate synthase

Question 3

Which one of the following compounds is required for biosynthesis of cytidine-5'-triphosphate (CTP) from carbamoyl-phosphate (in humans)?

A) N5-Methyltetrahydrofolate
B) Glycine
C) Glutamine
D) Succinic acid
E) GTP

Answer 3

Glutamine

Question 4

If insufficient quantities of 5-phosphoribosyl 1-pyrophosphate (PRPP) are present, an accumulation of which intermediate in the pyrimidine biosynthetic pathway will occur?

A) Carbamoyl phosphate
B) Carbamoyl aspartate
C) Dihydroorotate
D) Orotidine-5'-monophosphate
E) Orotic acid

Question 5

After a marathon race, a higher than normal plasma uric acid level is observed in the runner, because

A) the renal threshold for uric acid has been reached.
B) of a high ATP turnover.
C) of connective tissue anabolism.
D) of the unusually high turnover of muscle contractile proteins.
E) the catabolism of uric acid is dependent upon its conversion into a glycoconjugate.

Question 6

Transfer of the methyl group from 5-methyl tetrahydrofolate to homocysteine to form methionine requires

A) NADPH.
B) vitamin B₁₂.
C) FAD.
D) pyridoxal phosphate.
E) none of the above.

Question 7

M10621All of the following participate in de novo purine biosynthesis EXCEPT which one?

A) PRPP (5-phosphoribosyl 1-pyrophosphate)
B) ribose 5-phosphate
C) inosine 5'-phosphate
D) ribose 1-phosphate
E) glycine

Question 8

The reaction of hypoxanthine and PRPP (5'-phosphoribosylpyrophosphate) leads directly to the formation of

A) XMP.
B) AMP.
C) GMP.
D) IMP.
E) XDP.

Question 9

In the biosynthesis of purines the first purine derivative formed is

A) inosine.
B) inosine monophosphate.
C) guanosine monophosphate.
D) adenosine monophosphate.
E) xanthosine monophosphate.

Question 10

M12337Each of the following statements concerning de novo purine ribonucleotide synthesis in humans is correct EXCEPT which one?

A) The first step (committed step) utilizes PRPP in the synthesis of phosphoribosylamine.
B) Glutamine is a direct source of carbon atoms for the purine ring.
C) Tetrahydrofolate coenzymes function in the introduction of two carbon atoms.
D) IMP is an intermediate in the synthesis of both AMP and GMP.
E) De novo synthesis of guanylic acid (GMP) involves 3 enzymes which utilize glutamine.

Question 11

The deoxyribose of dCDP is made most directly from

A) ribose 5-phosphate.
B) ribulose 5-phosphate.
C) CDP.
D) PRPP.
E) none of the above.

Question 12

M12320The degradation of pyrimidines in man

A) results in formation of uric acid as end product.
B) results in formation of ammonium ion and carbon dioxide as end products.
C) is inhibited by allopurinol.
D) is blocked in orotic aciduria.

Question 13

All of the following are products of pyrimidine degradation EXCEPT

A) ammonia.
B) carbon dioxide.
C) aspartic acid.
D) beta-alanine.
E) beta-amino-isobutyric acid.

Question 14

In the de novo biosynthesis of uridine monophosphate (UMP), in mammals, each of the following occurs, EXCEPT:

A) C0₂ is incorporated in the formation of the pyrimidine ring.
B) PRPP is incorporated after the pyrimidine ring is formed.
C) A 1-C-THF metabolite is utilized.
D) C0₂ is produced (decarboxylation).
E) UTP is a feedback inhibitor of carbamoyl phosphate synthetase.

Question 15

The synthesis of UMP requires:

A) formate, aspartate and glycine.
B) bicarbonate, formate and glutamine.
C) ribose, glutamine and carbamoyl phosphate.
D) PRPP, aspartate and carbamoyl phosphate.
E) PRPP, aspartate and formate.

Question 16

The de novo biosynthesis of which of the following nucleotides would be the LEAST inhibited by methotrexate?

A) GMP
B) AMP
C) dTMP
D) UMP
E) IMP

Question 17

Adenylic acid is synthesized in a two step reaction sequence involving

A) inosinic acid, NAD+ and glutamine.
B) inosinic acid, ATP and glutamine.
C) inosinic acid, GTP and aspartate.
D) hypoxanthine and ribose-1-phosphate.
E) none of these.

Question 18

The distribution of inosine monophosphate (IMP) conversion to either guanosine monophosphate (GMP) or adenosinemonophosphate (AMP) is regulated by

A) feedback inhibition of phosphoribosylamine formation by GMP and/or AMP.
B) the requirement of GTP for AMP formation, and ATP for GMP formation.
C) availability of phosphoribosyl pyrophosphate (PRPP)
D) feedback inhibition of GMP on AMP formation and AMP on GMP formation.

Question 19

The chemotherapeutic agent, methotrexate, is a direct inhibitor of

A) thymidylate synthase.
B) aspartate transcarbamoylase.
C) dihydrofolate reductase.
D) PRPP synthase.
E) carbamoyl phosphate synthetase.

Question 20

Azaserine inhibits purine biosynthesis at the step

A) PRPP + glutamine -> 5-phosphoribosylamine.
B) 5-phosphoribosylamine + glycine -> 5-phosphoribosylglycineamide.
C) IMP -> AMP.
D) folic acid -> tetrahydrofolic acid (THFA).
E) none of the above.

Question 21

All carbon and nitrogen atoms of which of the following amino acids are incorporated into adenine?

A) Lysine
B) Glutamic acid
C) Alanine
D) Leucine
E) Glycine

Question 22

The last two reactions in uric acid production is catalyzed by

A) nucleoside phosphorylase.
B) an amino acid oxidase.
C) adenosine deaminase.
D) xanthine oxidase.
E) an endonuclease.

Question 23

This enzyme first recognizes allopurinol as a substrate and is then inhibited by the product of enzyme catalysis.

A) PRPP synthase
B) HGPRT (Hypoxanthine-guanine phosphoribosyl transferase)
C) Adenosine deaminase
D) PRPP amidotransferase
E) Xanthine oxidase

Question 24

The rate of synthesis of AMP is dependent on the concentration of all of the following EXCEPT which one?

A) IMP
B) GMP
C) ATP
D) AMP
E) UMP

Question 25

Derivatives of tetrahydrofolic acid participate in the synthesis of each of the following EXCEPT

A) adenosine triphosphate.
B) guanosine triphosphate.
C) thymidine triphosphate.
D) cytidine triphosphate.
E) S-adenosylmethionine.

Question 26

A common intermediate in the biosynthesis of both purine and pyrimidine nucleotides is

A) hypoxanthine.
B) phosphoribosylamine.
C) inosinic acid.
D) orotidine 5-phosphate.
E) phosphoribosyl pyrophosphate (PRPP).

Question 27

Which of the following compounds is parent, in the normal biosynthetic pathway, to the other purines within the cell?

A) Adenylic acid
B) Guanylic acid
C) Orotidylic acid
D) Inosinic acid
E) Xanthine

Question 28

M3069Which one of the following compounds is required for biosynthesis of adenosine-5'-phosphate (AMP) from inosine-5'-phosphate(IMP)?

A) Glutamine
B) Aspartate
C) ATP
D) Glycine
E) NAD

Question 29

Xanthine oxidase contains

A) copper.
B) zinc.
C) selenium.
D) molybdenum.
E) chromium.

Question 30

M16998The action of methotrexate on dihydrofolate reductase is an example of

A) a positive effector.
B) a negative effector.
C) a noncompetitive inhibitor.
D) a competitive inhibitor.
E) an irreversible inhibitor.

Question 31

In purine biosynthesis, which steps require the participation of tetrahydrofolic acid?

A) formation of phosphoribosylamine and glycinamide ribonucleotide
B) formation of alpha-N-formylglycinamide and 5-aminoimidazole-4- carboxamide ribonucleotide
C) carbon dioxide fixation forming 5-aminoimidazole-4-carboxylic acid and inosinic acid
D) formation of N-formylglycinamide ribonucleotide and 5-formamidoimidazole-4-carboxamide ribonucleotide
E) formation of inosinic acid and adenylosuccinic acid

Question 32

The product of the action of guanase (guanine aminohydrolase) on guanine is

A) Uric acid
B) Hypoxanthine
C) Guanosine
D) Xanthine
E) Both B and D

Question 33

Each of the following nucleic acid bases has a keto group EXCEPT which one?

A) uracil
B) thymine
C) cytosine
D) guanine
E) adenine

Question 34

An enzyme which is inhibited by allopurinol ribonucleotide.

A) PRPP synthase
B) HGPRT (Hypoxanthine?guanine phosphoribosyl transferase)
C) Adenosine deaminase
D) PRPP amidotransferase
E) Xanthine oxidase

Question 35

Which enzyme catalyzes the following reaction: allopurinol + PRPP --> allopurinol ribonucleotide + PPi.

A) Adenylate (AMP) deaminase
B) Xanthine Oxidase
C) PRPP amidotransferase
D) Hypoxanthine-Guanine phosphoribosyl transferase (HGPRT)
E) PRPP Synthase

Question 36

M12323Uric acid

A) in the urine reflects the turnover of the uridine nucleotide pool.
B) synthesis should increase on a low protein diet.
C) is an intermediate in the synthesis of purine nucleotides.
D) production produces significant amounts of energy for the cell.
E) is produced from xanthine in the degradation of adenine or guanine nucleotides.

Question 37

The source of carbons for purine synthesis de novo can be

A) glycine, aspartic acid, carbon dioxide, formate.
B) glycine, glutamine, carbon dioxide, formate.
C) glycine, aspartic acid, formate.
D) glycine, carbon dioxide, formate.
E) glycine, fumarate, glutamine, carbon dioxide.

Question 38

Hypoxanthine-guanine phosphoribosyl transferase (HGPRTase)

A) can catalyze the reaction between ribose 5-P and guanine to form GMP.
B) is involved in the de novo biosynthesis of pyrimidine nucleotides.
C) can catalyze the reaction between PRPP and guanine to form GMP.
D) is involved in the degradation of GMP to form guanine and PRPP
E) can catalyze the reaction between ribose and guanine to form GMP.

Question 39

What is contained within a nucleoside?

A) a ribose moiety, a nitrogenous base and a phosphate covalently attached to the ribose 5' carbon
B) a ribose moiety, a purine or pyrimidine, and a phosphate covalently linked to the 3' carbon of the ribose
C) a ribose moiety and a nitrogenous base
D) a deoxyribose, a purine or pyrimidine, and a phosphate linked to the ribose 5' carbon by a hydrogen bond

Question 40

In pyrimidine biosynthesis, the carbon atoms in the pyrimidine ring are supplied by

A) carbon dioxide and aspartic acid.
B) formyl tetrahydrofolate and aspartate acid.
C) carbon dioxide and succinate.
D) methylene tetrahydrofolate and succinate.
E) formyl tetrahydrofolate and succinic acid.

Question 41

Provides the number 3 nitrogen of the pyrimidine ring in the de novo biosynthesis of pyrimidine nucleotides (UMP).

A) Allopurinol
B) Carbamoyl phosphate
C) Theophylline
D) Serine
E) HCO₃ ^-

Question 42

Sources of the single carbons carried by tetrahydrofolic acid and used in purine biosynthesis include ________ and _________ .

A) alanine, glycine
B) serine, alanine
C) formate, serine
D) acetate, glycine
E) formate, acetate

Question 43

The inhibition of the synthesis of DNA by methotrexate results from direct inhibition of

A) a reaction in the pathway of purine biosynthesis.
B) thymidylate synthase.
C) the reduction of ribonucleotides to deoxyribonucleotides.
D) synthesis of S-adenosylmethionine.
E) the reduction of dihydrofolate to tetrahydrofolate.

Question 44

Which of the following is involved in formation of deoxyribonucleotides from ribonucleotides?

A) Thioredoxin
B) Dihydrofolate reductase
C) Hypoxanthine phosphoribosyl transferase
D) 5-Phosphoribosyl-1-pyrophosphate
E) Glutamine

Question 45

The action of methotrexate in inhibiting cell growth is based on its structural similarity to

A) xanthine oxidase.
B) dihydrofolate.
C) PABA.
D) S-adenosylmethionine.
E) tetrahydrobiopterin.

Question 46

The committed step in purine biosynthesis is

A) the formation of carbamoyl phosphate.
B) the formation of phosphoribosylamine pyrophosphate.
C) the formation of inosinic acid.
D) the formation of carbamoyl aspartate.

Question 47

All of the following enzymes play a role in the production of dTTP EXCEPT which one?

A) Thymidylate synthase
B) Deoxyuridine triphosphate phosphohydrolase
C) Deoxycytidylic acid aminohydrolase
D) Thymidine kinase
E) Cytosine deaminase

Question 48

M12321Absence or inhibition of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT) results in increased production of

A) uric acid.
B) creatinine.
C) adenine.
D) guanine.
E) hypoxanthine.

Question 49

All of the statements concerning Vitamin B₁₂ are CORRECT EXCEPT:

A) B₁₂ is primarily transported in the blood by binding to albumin.
B) The Schilling test helps confirm a B₁₂ deficiency.
C) Absorption of B₁₂ occurs in the terminal ileum.
D) In B₁₂ deficiency, urinary methyl malonate excretion increases.
E) Removal of the stomach could lead to a deficiency of B₁₂.

Question 50

M12332The formation of purine deoxyribonucleotides from the corresponding ribonucleotides

A) does not involve UDP because there is no need for dUDP in DNA synthesis.
B) requires an enzyme that utilizes tetrahydrofolic acid to reduce a disulfide protein.
C) results from the deoxygenation of the sugar at the nucleoside diphosphate level.
D) is controlled by the level of the ribonucleoside monophosphates in the cell.
E) is unimportant in the overall regulation of DNA replication.

Question 51

Which of the following enzymes is not subject to feedback inhibition by purine nucleotides?

A) glutamine PRPP amidotransferase
B) PRPP synthase
C) inosinate dehydrogenase
D) xanthine oxidase
E) adenylosuccinate synthetase

Question 52

M12234Which of the following is an inhibitor of the committed step in pyrimidine biosynthesis in mammals?

A) UTP
B) carbamoyl phosphate
C) PRPP
D) N-carbamoyl aspartate
E) orotic acid

Question 53

All of the following are important for the regulation of plasma urate concentrations EXCEPT

A) the allosteric regulation of PRPP synthase.
B) the proper balance between secretion and reabsorption of uric acid by the kidney.
C) the efficient conversion of hypoxanthine and guanine to nucleotides.
D) the feedback inhibition of amidophosphoribosyl transferase.
E) the induction of intestinal xanthine oxidase.

Question 54

In the biosynthesis of the nucleotide coenzyme NAD⁺:

A) The major part of an ATP molecule is structurally incorporated into the NAD+ molecule.
B) The major part of a PRPP molecule is structurally incorporated into the NAD+ molecule.
C) Both
D) Neither

Question 55

Which of the following characterizes a DIFFERENCE involved in the de novo biosynthesis of purines and pyrimidines?

A) Pentose phosphate is added before completion of a heterocyclic ring system in one case, and not the other.
B) One heterocyclic ring system is synthesized from low molecular weight precursors, the other is not.
C) The synthesis of one ring system involves the use of ATP as an energy source, the other does not.
D) Asparagine is a precursor in one case, and not the other.
E) The amino group of glutamate is an immediate precursor in the synthesis of one ring system, and not the other.

Question 56

Which compound is an inhibitor of dihydrofolate reductase?

A) azaserine
B) fluorouracil
C) folic acid
D) methotrexate
E) 3-azido-2,3-dideoxythymidine

Question 57

In mammalian cells the nitrogen atoms of the purine ring are derived from

A) aspartate, glutamine and glycine.
B) ammonia, glutamine and aspartate.
C) urea and ammonia.
D) glycine, ammonia and glutamate.
E) glycine and aspartate.

Question 58

The possible connection between Vitamin B12 and folic acid in metabolism occurs in

A) glycolysis.
B) the conversion of methylmalonyl CoA to succinyl CoA.
C) the conversion of homocysteine to methionine.
D) the methylation of pyrimidine bases.
E) the synthesis of proteins.

Question 59

In de novo pyrimidine biosynthesis, which of the following compounds is an IMMEDIATE precursor in the reaction in which a cytosine nucleotide is produced?

A) UTP
B) UDP
C) UMP
D) Orotidine 5'-phosphate
E) None of the above.

Question 60

The de novo biosynthesis of AMP in human tissues has a specific requirement for each of the following EXCEPT

A) glycine.
B) ATP.
C) xanthine.
D) PRPP (5-phosphoribosyl-1-pyrophosphate).
E) aspartic acid.

Question 61

Conversion of a ribose residue to a 2-deoxyribose residue can occur in mammalian tissues in a reaction which may be described as a(n)

A) reduction of UMP.
B) oxidation of UMP.
C) reduction of UDP.
D) oxidation of UDP.
E) reduction of UTP.

Question 62

Purine biosynthesis is subject to allosteric feedback inhibition by

A) CDP.
B) UDP.
C) TMP.
D) CMP.
E) AMP.

Question 63

Which one of the following reactions is inhibited by high levels of AMP?

A) Xanthosine-5'-monophosphate + glutamine + ATP ==> Guanosine-5'- monophosphate + Glutamate + ADP + Pi
B) Inosine-5'-monophosphate + Aspartate + GTP ==> Adenylosuccinate + GDP + Pi
C) Adenylosuccinate ==> Adenosine-5'-monophosphate + Fumarate
D) Inosine-5'-monophosphate + NAD⁺ +H20 ==> Xanthosine -5'-monophosphate + NADH + H⁺

Question 64

A nucleotide intermediate common to the synthesis of all the pyrimidine mononucleotides is

A) CMP.
B) UMP.
C) TMP.
D) UTP.
E) UDP.

Question 65

Negative control of ribonucleotide reductase involves mainly

A) dUMP.
B) UTP.
C) dATP.
D) ATP.
E) CDP.

Question 66

The enzyme, hypoxanthine-guanine phosphoribosyl transferase

A) is defective in most cases of clinical gout.
B) allows free purines to be reutilized for incorporation into DNA.
C) forms nucleosides as one product.
D) runs out of control in Lesch-Nyhan syndrome.
E) makes a product which stimulates the de novo biosynthesis of purine nucleotides.

Question 67

The main catabolic product (i.e., urinary excretion product) of purine metabolism in man is

A) urea.
B) ammonia.
C) creatinine.
D) uric acid.
E) inosinic acid.

Question 68

Which of the following is an anti-folate chemotherapeutic agent?

A) Methotrexate
B) Azaserine
C) Cytosine arabinoside
D) 5-Fluorouracil
E) 5-Azacytidine

Question 69

C

A) folic acid.
B) dihydrofolic acid.
C) tetrahydrofolic acid.
D) 5-methyl-tetrahydrofolic acid.
E) none of the above.

Question 70

Tetrahydrofolic acid is essential for DNA synthesis because it is required for the conversion of

A) UDP -> dUDP.
B) dCMP -> dUMP.
C) thioredoxin disulfide -> thioredoxin sulfhydryls.
D) dUMP -> dTMP.
E) none of the above.

Question 71

The formation of deoxyribonucleotides involves which of the following processes?

A) reduction of ribose in monophosphates
B) reduction of ribose in diphosphates
C) reduction of ribose in triphosphates
D) reduction of ribose in 5-phosphoribosyl pyrophosphate (PRPP) and subsequent reaction with a purine or pyrimidine.
E) oxidation of ribose in diphosphates

Question 72

A compound which contributes both carbon and nitrogen atoms to pyrimidine ring biosynthesis is

A) glycine.
B) glutamine.
C) serine.
D) aspartic acid.

Question 73

M12326Xanthine is

A) a purine base.
B) the precursor of uric acid in a reaction catalyzed by xanthine oxidase.
C) an intermediate in the degradation of adenine and guanine nucleotides.
D) in nucleotide form, a precursor of GMP.
E) all of the above.

Question 74

M12233The enzyme which catalyzes the committed step in the biosynthesis of pyrimidine nucleotides in humans is

A) mitochondrial carbamoyl phosphate synthetase I.
B) dihydroorotatase.
C) aspartate transcarbamoylase.
D) orotidylate decarboxylase.
E) cytoplasmic carbamoyl phosphate synthetase II.

Question 75

Which one of the following statements relating to the thymidylate (dTMP) synthase reaction is FALSE?

A) dUMP is a substrate for this enzymatic reaction.
B) A 1-carbon THF is a substrate for this enzymatic reaction.
C) NADPH is a substrate for this enzymatic reaction.
D) F-dUMP directly inhibits this enzymatic reaction.
E) Dihydrofolate (DHF) is produced by this enzymatic reaction.

Question 76

M11007Which statement regarding the biosynthesis of thymine incorporated into DNA is correct?

A) A methyl group is transferred to deoxyuridine monophosphate from methionine.
B) A methyl group is transferred to deoxycytidine monophosphate from 5-methyl tetrahydrofolate (THF).
C) A one-carbon unit is transferred to deoxyuridine monophosphate from 5,10-methylene THF accompanied by oxidation of the THF.
D) A methyl group is transferred to deoxyuridine monophosphate from 5-methyl THF and the THF is oxidized.
E) The enzyme which forms (d)TMP is the primary target of the anti- cancer drug, Methotrexate.