nucleotides

Question 1

Which of the following is NOT a nucleoside?
A. Adenosine
B. Uridine
C. Cytosine
D. Guanosine
E. Inosine

Answer 1

C. cytosine

Question 2

nucleoside?

Answer 2

ribose+nucleobase

Question 3

nucleotide

Answer 3

nucleoside+phosphate

Question 4

De novo synthesis of purine bases

Answer 4

-makes purine bases from scratch
-utilizes amino acids as carbon and nitrogen donors
-costly in terms of energy: uses ATP in many steps
-PRPP is key starting material

Question 5

The first step in synthesis of purine base is the _____ and is ________ regulated

Answer 5

-commitment step
-highly regulated

Question 6

What is a common intermediate for both AMP and GMP synthesis

Answer 6

IMP

Question 7

The commitment step for de novo purine synthesis is ______ by AMP and GMP as well as IMP

Answer 7

supresses

Question 8

PRPP _____ the commitment step.

Answer 8

stimulates

Question 9

____ and _____ suppress their synthesis from IMP

Answer 9

AMP and GMP

Question 10

GDP and GTP are produced from GMP using
ATP as a _____

Answer 10

phosphate donor.

Question 11

Salvage pathway

Answer 11

-Hypoxanthine-guanine phosphoribosyl transferase (HGPRTase)
-Adenine phosphoryl transferase (APRTase)
-Pyrimidine phosphoryl transferase

Question 12

De novo synthesis of pyrimidine bases

Answer 12

-Orotate is synthesized from amino acids and HCO 3-.
-OMP is synthesized from orotate and PRPP, which is
analogous to the salvage pathway.
-UDP and UTP are produced from UMP using ATP as a
phosphate donor.
-CTP is produced from UTP.

Question 13

Hypoxanthine-guanine phosphoribosyl transferase (HGPRTase)

Answer 13

-hypoxanthine + PRPP ⇄ IMP + PP i
-guanine + PRPP ⇄ GMP + PPi

Question 14

Adenine phosphoryl transferase (APRTase)

Answer 14

adenine + PRPP ⇄ AMP + PP i

Question 15

adding phosphate groups

Answer 15

-Both de novo synthesis and salvage pathways generate nucleoside monophosphate
(NMP).
-Nucleotide kinases add phosphate groups to NMP and NDP.
-ATP is the major phosphate donor.

Question 16

degradation of purine bases

Answer 16

-Purine nucleoside phosphorylase
removes nucleobases from nucleosides.
-The end product of purine nucleobases is
uric acid.

Question 16

uric acid

Answer 16

-Uric acid is not so soluble.
-May form needle-like sodium urate crystals
-Deposition of sodium urate crystals in joints
causes gout

Question 17

gout

Answer 17

-Patients show elevated levels of uric acids (hyperuricemia).
-Causes
(Overproduction of purine bases by de novo synthesis, Decreased excretion of uric acid, Alcohol and high-fructose diet)

Question 18

gout and allopurinol

Answer 18

-Structural isomer of hypoxanthine
-Xanthine oxidase inhibitor
-Reduces the production of uric acid.
-Increases the utilization of hypoxanthine through the
salvage pathway, which reduces de novo purine
synthesis

Question 19

synthesis of depxyribose nucleotides

Answer 19

-dNTP is necessary for DNA replication and repair.
-Ribonucleotide reductase converts NDP to dNDP, which is the rate-limiting
step for dNTP synthesis.
-Ribonucleotide reductase is allosterically regulated by many NTPs and dNTPs.
-NADPH is used as a reducing cofactor.

Question 20

synthesis of thymine

Answer 20

-DNA contains thymine instead of uracil.
-Thymidylate synthase converts dUMP to dTMP.
-N 5,N 10-methylene tetrahydrofolate (THF) acts as the methyl donor.

Question 21

synthesis of NAD+

Answer 21

-Nicotinamide adenine dinucleotide
-Nicotinamide is a vitamin (niacin; vitamin B 3).
-The first step is analogous to the salvage pathway in which PRPP acts as a ribose 5-phosphate donor.

Question 22

6-mercaptopurine (6-MP)

Answer 22

-antitumor drug
-converted to a mononucleotide through the salvage pathway
-The mononucleotide is a potent negative regulator of PRPP-amidotransferase, the
enzyme catalyzing the commitment step of de novo purine synthesis.
-Metabolized to 6-thiouric acid by xanthine oxidase

Question 23

_____ and ____ are used together to potentiate the drug activity by inhibiting degradation.

Answer 23

allopurinol and 6-mercaptopurine (6-MP)

Question 23

5-fluorouracil

Answer 23

-Antitumor drug
-Analog of uracil
-Converted to FUMP and FdUMP in cells
-FUMP is incorporated into RNA and interferes with RNA processing.

Question 24

FdUMP inhibits _________ irreversibly by forming a covalent bond.

Answer 24

thymidylate synthase

Question 25

Without dTTP, cells undergo ________, whose mechanism is not well known yet.

Answer 25

“thymineless death”

Question 26

acyclovir

Answer 26

-Antiviral drug used to treat herpes simplex virus
(HSV) infections
-Converted to the monophosphate by a HSV-
thymidine kinase, which exists only in the infected
cells.
-The triphosphate is used as a substrate for the
HSV DNA polymerase, causing chain
termination

Question 27

______an esterifed version of acyclovir with valine, is a prodrug with a greater oral
bioavailability.

Answer 27

valacyclovir

Question 28

sofosbuvir (sovaldi)

Answer 28

-Antiviral drug used to treat hepatitis C
-Prodrug; rapidly converted to the active agent in vivo.
-Activation of the corresponding nucleoside is much slower.
-The active agent is a potent inhibitor of NS5B, which is a RNA-dependent RNA
polymerase