Review 9: Purine and Pyrimidine Metabolism Flashcards
What makes up a nucleotide? a nucleoside?
base (purine or pyrimidine), pentose (ribose or deoxyribose), and a phosphoryl group
Nucleoside is everything but the phosphate
What are the purines?
adenine and guanine
What are the pyrimidines?
thymine and cytosine (and uracil)
True or False: both purines and pyrimidines are nonessential
TRUE (both are synthesized by essential precursors)
Purine can be synthesized from _____________, ___________________, and ___.
amino acids, tetrahydrofolate derivative, and CO2
Pyrminidines can be synthesized from __________ and ___.
aspartate and glutamine and CO2
What is the first formal step of purine synthesis?
activation of ribose 5-phosphate to give PRPP
Why are drugs that target purine biosynthesis so effective in cancers?
tumors rely on purine biosynthesis whereas normal cells recycle their bases
The sources of the atoms in the pyrimidine ring are _________, _______, and ____.
glutamine, aspartate, and CO2.
The regulated first step in pyrimidine synthesis is catalyze by which enzyme?
carbomoyl phosphate synthetase II
What is the precursor for other pyrimidines?
UMP
dUMP goes on to synthesize ______ and __ __ ________
dTMP and N5, N10 methylene tetrahydrofolate
via thymidylate synthase
How does the antitumor drug 5-fluorouracil work?
gets converted to f-dUMP which acts as a pseudosubstrate and covalently binds to and inhibits thymidylate synthase
SUICIDE INHIBITOR
How does Methotrexate work?
competitive inhibitor of dihydrofolate reductase and increases dihydrofolate causing a tetrahydrofolate deficiency
What enzyme converts dUMP to dTMP?
thymidylate synthase and N,N methylene tetrahydrofolate
What enzyme catalyzes the formation of deoxyribose from ribose?
ribonucleotide reductase (2’ hydroxyl group of ribose is replaced with hydrogen)
thioredoxin is a cofactor
DNA synthesis takes place during the ___ phase of the cell cycle
S
What 2 enzymes increase dramatically during the S phase?
1) ribonucleotide reductase
2) thymidylate synthase
What is the enzyme of the Salvage Pathway?
HGPRTase (hypoxanthine-guanine phosphoribosyltransferase)
What is the salvage pathway?
the recycling of purines
What disease is caused by a deficiency of HGPRTase?
Lesch-Nyhan syndrome
What is the final product of purine degradation?
uric acid
What enzyme catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid?
xanthine oxidase
What are the 2 tautomeric forms of uric acid?
1) uric acid (dominates at urine pH)
2) urate (dominates at blood pH)
