Metabolism of Nucleotides Flashcards
The two pathways that lead to nucleotides
De novo and salvage
What is the difference between the two pathways of nucleotides?
De novo pathways get precursors from metabolism of other macromolecules, salvage pathways recycle free bases and nucleotides from nucleic acid breakdown
Which product of the urea cycle is required in pyrimidine synthesis?
Carbamoyl phosphate
What is the difference between carbamoyl phosphate of the urea cycle and carbamoyl phosphate of the pyrimidine synthesis in terms of synthesis?
That of pyrimidine synthesis is formed by the cytosolic enzyme carbamoyl phosphate synthetase II, while that of the urea cycle is formed by the mitochondrial enzyme carbamoyl phosphate synthetase I
In the purine de novo pathway, which is the first intermediate with a complete purine ring>
Inosinate (IMP)
What is the first committed intermediate to purine de novo pathway?
5’-Phosphorybosylamine
What is the first committed intermediate of pyrimidine de novo pathway?
N-carbamoylaspartate
Which amino acids contribute atoms for purine de novo pathway?
Asp, Gly, Gln
Which three enzyme of the pyrimidine de novo pathway are part of a single trifunctional protein?
The first three: carbamoyl phosphate synthetase II, aspartate transcarbamoylase, and dihydroorotase
Which nucleotide pathway needs carbamoyl phosphate?
Pyrimidine de novo pathway
How is pyrimidine nucleotide biosynthesis regulated?
By feedback inhibition of product CTP to aspartate transcarbamoylase
Which of the following will differentiate GDP from dGDP?
A. dGDP has an extra amino group attached to carbon 6 in
the purine ring
B. dGDP has an extra phosphate attached to the 2’-carbon of the ribose
C. dGDP is reduced at the 2’-carbon of the ribose
D. dGDP is a purine nucleotide while GDP is a pyrimidine nucleotide
C
What is the common nitrogen containing metabolite needed for the biosynthesis of NAD+, FAD and Coenzyme A?
A. AMP
B. CMP
C. GTP
D. CTP
A
In which of the following pathways is Phosphoribosyl pyrophosphate (PRPP) NOT a direct, activated reactant?
A. de novo synthesis of purine nucleotides
B. thymidylate synthesis
C. de novo synthesis of pyrimidine nucleotides
D. salvage of purine bases
B
Carbon atoms from tetrahydrofolate derivatives are incorporated by de novo synthesis into which of the following nucleotides?
A. The purine but not the pyrimidine nucleotides found in RNA
B. The pyrimidine but not the purine nucleotides found in RNA
C. All deoxyribonucleotides but no ribonucleotides
D. All ribonucleotides but no deoxyribonucleotides
A
Which of the following will differentiate de novo purine nucleotide biosynthesis from pyrimidine nucleotide synthesis?
A. ATP hydrolysis B. Incorporation of glycine C. One-carbon transfer from activated derivatives of tetrahydrofolate (THF) D. Regulation by feedback inhibition E. PRPP as a source of ribose
B
Which of the following statements regarding regulation of purine synthesis is CORRECT?
A. GMP and AMP activate PRPP synthetase, which catalyzes the activation step
B. IMP inhibits PRPP synthetase
C. Low levels of GTP activates ATP synthesis
D. Low levels of ATP activates GTP synthesis
E. PRPP amidotransferase, which catalyzes the committed step, is inhibited by both GMP and AMP
E
Which of the following is TRUE about pyrimidine synthesis?
A. assembly of the 6-membered ring directly on the PRPP backbone
B. involves carbamoyl phosphate synthetase II (CPS II)
C. PRPP amidotransferase
D. IMP as the first pyrimidine monophosphate formed
B
An 18-month old boy was brought to the clinic because of severe repeated lip chewing and aggressive tongue biting. A diagnosis of Lesch-Nyhan syndrome was made on the basis of biochemical analysis. Which of the following reactions is most likely to be deficient in this boy?
A. attachment of 5-phosphoribosyl-1-pyrophosphate (PRPP) to guanine
B. condensation of ornithine with carbamoyl phosphate
C. deamination of Adenosine
D. hydroxylation of phenylalanine
A
Which of the following is a product of the major purine salvage pathway?
A. Cytidylate B. Guanosine monophosphate C. Inosine D. Uric acid E. Hypoxanthine
B
Which of the following is the main urinary excretion product of purine nucleotide metabolism in humans?
A. Ammonia B. Bilirubin C. Uric acid D. Glutamine E. Urea
C
Which enzyme catalyzes the reduction of ribonucleotides?
Ribonucleotide reductase
Ribonucleotides are the precursors of deoxyribonucleotides. T/F
T
The pair of H atoms needed to reduce ribose is donated by which molecule?
NADPH
The catabolism of thymine produces an intermediate that can enter the catabolism of an amino acid. What is this intermediate?
Methylmalonyl-semialdehyde
The end product of the catabolism of thymine is an intermediate of the catabolism of which amino acid?
Val
The catabolism of pyrimidines lead to the production of which excretory product?
Urea
The catabolism of purines lead to the production of which excretory product?
Uric acid
Which of the following conditions would contribute to hyperuricemia and gout?
A. reduced activity of PRPP synthetase
B. reduced feedback inhibition of the committed step in purine biosynthesis
C. reduced activity of xanthine oxidase
D. hyperactive hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
D
Which of the following will be affected by the use of allopurinol?
A. Hypoglycemia by inducing gluconeogensis
B. Hyperammonemia by inhibiting synthesis of urea
C. Hyperlipidemia by stimulating beta oxidation
D. Hyperuricemia by inhibiting purine nucleotide degradation
D
Which of the following is not common for the catabolic pathways of purines and pyrimidines?
A. Removal of phosphate
B. Removal of sugar
C. Deamination
D. Hydrolysis to open ring structure
D
Methotrexate and 5-fluorouracil are both used for cancer chemotherapy. Which of the following will result if both drugs were used simultaneously?
A. The drugs would directly block synthesis of all deoxyribonucleotides.
B. Both drugs would directly inhibit purine nucleotide biosynthesis.
C. Both drugs would directly inhibit pyrimidine nucleotide biosynthesis.
D The effects of the two drugs will cancel each other out.
E. The combined effect will be to dramatically inhibit thymidylate synthase.
E
What is the 1st nucleotide formed in the de novo purine synthesis?
A. Inosine monophosphate
B. Carbamoyl phophate
C. Cytidine monophosphate
D. Orotidine monophosphate
A
Which of the following is likely to occur in human cells deficient for HGPT?
A. Salvage pyrimidine decreases
B. Salvage purine increases
C. Uric acid increases
D. Decrease in deoxyribose
C
A patient is undergoing a chemotherapy treatment for a tumor. The effect of the therapy is damage to the tumor cells. Days after the chemo session, the patient is complaining of inflamed big toe. What mechanism explains the inflammation of the big toe?
A. Salvage pathway of Purine
B. De novo synthesis of purine
C. Purine Catabolism
D. Pyrimidine synthesis
C
The following are included in determining nitrogen content in the body?
A. Uric Acid B. NH3 C. Creatinine D. A and B Only E. All of the above.
E
Uric acid as waste product: purine or pyrimidine?
Purine
Not excreted as waste product: purine or pyrimidine?
Pyrimidine
Of the three main components of a nucleotide, which is formed last in purine de novo synthesis?
Nitrogenous base
Which part of the purine ring is first formed during de novo synthesis?
N-9
The first part of the purine ring formed during de novo synthesis is donated by which molecule?
Gln
C-8 and C-2 of the purine ring is donated by which molecule in de novo synthesis?
N10-formyltetrahydrofolate (formate)
N-3 of the purine ring is donated by which molecule in de novo synthesis?
Gln
N-1 of the purine ring is donated by which molecule in de novo synthesis?
Asp
How many ATP is required for purine de novo synthesis?
6
XMP is an intermediate in the synthesis of which purine: GMP or AMP?
GMP
Of the three components of a nucleotide, which is synthesized first in pyrimidine de novo pathway?
Nitrogenous base
A 42-year-old male cancer patient undergoing radiation therapy develops severe pain in his right big toe.
Laboratory analyses indicate an elevated serum uric
acid level and urate crystals in his urine. This
patient’s pain is caused by the overproduction of the
end product of which of the following metabolic pathways?
A. De novo pyrimidine biosynthesis B. Pyrimidine degradation C. De novo purine biosynthesis D. Purine salvage E. Purine degradation
E
The patient’s paincaused by gout, resulting from the crystallization of excess uric acid n his joints. The cel death caused by radiation therapy leads to the degradationof
nucleic acids from those cells.
The degradation of purines from these nucleic acids results in excess production of uric relatively insoluble
compound that can cause kidney stones, as well as gout.
The end products of pyrimidine degradation do not cause these problems, because they are all soluble compounds
that can be more easily excreted n the urine.
A one-year-old female patient is lethargic, weak, and
anemic. Her height and weight are both low for her
age. Her urine contains an elevated level of orotic
acid. The administration of which of the following
compounds is most likely to alleviate her symptoms?
A. Thymidine B. Uridine C. Hypoxanthine D. Guanine E. Adenin
B
The elevated excretion of orotic acid indicates that the patient has orotic aciduria, a genetic disorder affecting the de novo pyrimidine biosynthetic pathway.
Deficiencies n the enzyme activities OMP decarboxylase and/or orotate phosphoribosyltransferase (both of which are
domains of the enzyme synthase) leave the patient unable
to synthesize any pyrimidines.
Uridine, a pyrimidine nucleoside, is useful in treating this disorder because it bypasses the missing enzymes, and can be converted to all the other pyrimidines.
Although thymidine is a pyrimidine nucleoside, cannot be converted to other pyrimidines. Hypoxanthine, guanine, and adenine are all purine bases that have no value helping to replace the missing pyrimidines.
The rate of DNA synthesis in a culture of cells could
be most accurately determined by measuring the
incorporation of which of the following radioactive
compounds?
A. Phosphate B. Adenine C. Guanine D. Thymidine E. Uridine
D
Because thymidine is essentially found only in DNA, its incorporation would most accurately reflect the rate of DNA synthesis. Uridine is found only in RNA and could be used to measure the rate of RNA synthesis. Phosphate,
adenine, and guanine are present in both DNA and RNA, and could not be used to specifically measure synthesis of either one.
After several weeks of chemotherapy in the form of
methotrexate, a cancer patient’s tumor begins to
show signs of resistance to treatment. Which of the
following mechanisms is most likely to explain the
tumor’s methotrexate resistance?
A. Overproduction of dihydrofolate reductase B. Overproduction of xanthine oxidase C. Deficiency of PRPP synthase D. Deficiency of thymidine kinase E. Deficiency of synthase
A
Methotrexate interferes with folate metabolism by acting as a competitive inhibitor of the enzyme dihydrofolate reductase. This starves cells for tetrahydrofolate, and
makes them unable to synthesize purines and dTMP. This s especially toxic to rapidly-growing cancer cells. Overproduction of dihydrofolate reductase, usually caused by amplification of its gene, can overcome the inhibition of the enzyme at the methotrexate concentrations used for
chemotherapy, and can result n resistance of the tumor to treatment by this drug.
Similarities between carbamoyl phosphate synthetase I and carbamoyl phosphate synthetase II include which ONE of the following?
(A) Carbon source (B) Intracellular location (C) Nitrogen source (D) Regulation by N-acetylglutamate (E) Regulation by UMP
A
Lesch-Nyhan syndrome is due to an inability to catalyze which of the following reactions?
(A) Adenine to AMP (B) Adenosine to AMP (C) Guanine to GMP (D) Guanosine to GMP (E) Thymine to TMP (F) Thymidine to TMP
C
Allopurinol can be used to treat gout because of its ability to inhibit which one of the following reactions?
(A) AMP to XMP (B) Xanthine to uric acid (C) Inosine to hypoxanthine (D) IMP to XMP (E) XMP to GMP
B
Which of the following statements regarding regulation of purine synthesis is CORRECT?
A. GMP and AMP activate PRPP synthetase, which catalyzes the activation step
B. IMP inhibits PRPP synthetase
C. Low levels of GTP activates ATP synthesis
D. Low levels of ATP activates GTP synthesis
E. PRPP amidotransferase, which catalyzes the committed step, is inhibited by both GMP and AMP
E
Which is/are true of dietary nucleic acids?
a. Ingested with associated proteins
b. Digested to free bases, deoxyribose/ribose and phosphate in GIT
c. Used for the synthesis of endogenous nucleotide
d. AOTA
e. A and B
e
Which is true of purine and pyrimidine nucleotide?
a. Synthesized from simple metabolic precursor
b. Salvaged from preformed nucleosides and free bases
c. Can be acquired from proteins in the diet
d. AOTA
e. A and B
e
Which molecule donates both carbon and nitrogen atoms to be purine ring?
a. Aspartate
b. Glycine
c. Glutamate
d. Cysteine
e. Lysine
B
Which pair contributes both C atoms to pyrimidine synthesis?
a. Tyrosine and Ribulose-5-phosphate
b. Carbamoyl phosphate and Aspartate
c. Tryptophan and Carbamoyl Phosphate
d. Aspartate and THF
b
Which of the following is NOT a negative feedback effector/regulator for pyrimidine biosynthesis?
a. IMP
b. AMP
c. GMP
d. UMP
d
Involved in the salvage of pyrimidine
a. Cystidine and Uridine
b. Nucleotide kinase
c. ATP
d. AOTA
d
What ncharacteristic cannot be used to differentiate CPS I and CPS II?
a. Cellular location
b. Source of nitrogenous base
c. Type of reaction
d. Reulation in the metabolic pathway
c
Which is true of thymidine monophosphate synthesis?
a. Catalyzed by thymidylate synthase
b. Involves transfer of one-carbon group from THF
c. Inhibited by F-deoxyUMP coming from the drug 5-Fluoroacil
d. AOTA
d
Which of the following is/are products in the catabolism of purine and pyrimidine nucleotides?
a. Uric acid
b. CO2 and ammonia
c. Beta-alanine
d. AOTA
e. A nd B only
d
Site of action of allopurinol:
a. Conversion of hypoxanthine to IMP
b. Degradation of hypoxanthine to xanthine and uric acid
c. Synthesis of PRPP from ATP and ribose-5-phosphate
d. Phosphoribosylation of guanine
b
