Review 9: Purine and Pyrimidine Metabolism

Question 1

What makes up a nucleotide? a nucleoside?

Answer 1

base (purine or pyrimidine), pentose (ribose or deoxyribose), and a phosphoryl group

Nucleoside is everything but the phosphate

Question 2

What are the purines?

Answer 2

adenine and guanine

Question 3

What are the pyrimidines?

Answer 3

thymine and cytosine (and uracil)

Question 4

True or False: both purines and pyrimidines are nonessential

Answer 4

TRUE (both are synthesized by essential precursors)

Question 5

Purine can be synthesized from _____________, ___________________, and ___.

Answer 5

amino acids, tetrahydrofolate derivative, and CO2

Question 6

Pyrminidines can be synthesized from __________ and ___.

Answer 6

aspartate and glutamine and CO2

Question 7

What is the first formal step of purine synthesis?

Answer 7

activation of ribose 5-phosphate to give PRPP

Question 8

Why are drugs that target purine biosynthesis so effective in cancers?

Answer 8

tumors rely on purine biosynthesis whereas normal cells recycle their bases

Question 9

The sources of the atoms in the pyrimidine ring are _________, _______, and ____.

Answer 9

glutamine, aspartate, and CO2.

Question 10

The regulated first step in pyrimidine synthesis is catalyze by which enzyme?

Answer 10

carbomoyl phosphate synthetase II

Question 11

What is the precursor for other pyrimidines?

Answer 11

UMP

Question 12

dUMP goes on to synthesize ______ and __ __ ________

Answer 12

dTMP and N5, N10 methylene tetrahydrofolate

via thymidylate synthase

Question 13

How does the antitumor drug 5-fluorouracil work?

Answer 13

gets converted to f-dUMP which acts as a pseudosubstrate and covalently binds to and inhibits thymidylate synthase

SUICIDE INHIBITOR

Question 14

How does Methotrexate work?

Answer 14

competitive inhibitor of dihydrofolate reductase and increases dihydrofolate causing a tetrahydrofolate deficiency

Question 15

What enzyme converts dUMP to dTMP?

Answer 15

thymidylate synthase and N,N methylene tetrahydrofolate

Question 16

What enzyme catalyzes the formation of deoxyribose from ribose?

Answer 16

ribonucleotide reductase (2’ hydroxyl group of ribose is replaced with hydrogen)

thioredoxin is a cofactor

Question 17

DNA synthesis takes place during the ___ phase of the cell cycle

Answer 17

S

Question 18

What 2 enzymes increase dramatically during the S phase?

Answer 18

1) ribonucleotide reductase

2) thymidylate synthase

Question 19

What is the enzyme of the Salvage Pathway?

Answer 19

HGPRTase (hypoxanthine-guanine phosphoribosyltransferase)

Question 20

What is the salvage pathway?

Answer 20

the recycling of purines

Question 21

What disease is caused by a deficiency of HGPRTase?

Answer 21

Lesch-Nyhan syndrome

Question 22

What is the final product of purine degradation?

Answer 22

uric acid

Question 23

What enzyme catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid?

Answer 23

xanthine oxidase

Question 24

What are the 2 tautomeric forms of uric acid?

Answer 24

1) uric acid (dominates at urine pH)

2) urate (dominates at blood pH)

Question 25

What causes gout?

Answer 25

excessive production or underexcretion of uric acid

Question 26

What is hyperuricemia?

Answer 26

elevated urate in blood - leads to deposition of sodium urate crystals in joints

Question 27

What is hyperuricosuria?

Answer 27

elevated uric acid in urine - can lead to uric acid stones in the kidney

Question 28

How do you treat gout?

Answer 28

inhibit xanthine oxidase (with drug allopurinol)