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21 Cards in this Set

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  • Back
What are the major differences between purine and pyrimidine pathways? What are the similarities?
similarities: start with R-5-P from HMP shunt, PRPP synthetase catalyzes rate limiting step, most active during DNA replication
differences: pyrimidine pathway is a straight chain whereas purines branch, pyrimidines use carbomoyl phosphate synthetase II (CPSII) for the first committed step whereas purines use glutamine-PRPP-amidotransferase, pyrimidine pathway is 4 steps whereas purines is 11
What is the significance of using multifunctional enzymes to produce UMP from glutamine?
minimizes degradation of intermediates, maintains reaction specificity, conserves energy, increases speed and efficiency
What enzyme catalyzes the rate limiting step and the first committed step in pyrimidine synthesis?
PRPP synthetase is rate limiting, carbamoyl phosphate synthetase II (CPS II) is first committed
What is the first pyrimidine and first pyrimidine nucleotide formed in pyrimidine synthesis?
orotate is first pyrimidine, OMP is first pyrimidine nucleotide
How is CPS II regulated?
positive allosteric effectors: PRPP, ATP
negative allosteric effector: UTP
From OMP, what is the process that leads to the formation of UTP, CTP?
OMP → UMP (nucleoside monophosphate kinase) → UDP (nucleoside diphosphate kinase) → UTP (CTP synthetase) → CTP
From OMP, what is the process that leads to the formation of TMP?
OMP → UMP (nucleoside monophosphate kinase) → UDP (ribonucleotide reductase) → dUDP → dUMP (thymidylate synthase) → dTMP
What is the rate limiting enzyme in the formation of deoxyribonucleotides and what is the required coenzyme?
rate limiting enzyme is ribonucleotide reductase, thioredoxin(reduced) is the coenzyme
How is ribonucleotide reductase regulated?
allosteric activator: ATP
allosteric inhibitor: dATP
(also has a substrate specific site)
What is adenosine deaminase (ADA) deficiency?
autosomal recessive disorder that leads to immunodeficiency, results in accumulation of adenosine (leads to production of excess dATP and deficiency of other dNTPs)
What does thymidylate synthase do, when is it most active, and what does it require to work?
rate limiting enzyme (during S-phase) in the formation of dTMP from dUMP, requires methylene tetrahydrofolate
Which purines and/or pyrimidines do not require tetrahydrofolate?
pyrimidines UTP and CTP
What enzyme regenerates tetrahydrofolate, and how does it do this?
dihydrofolate reductase, converts folic acid into tetrahydrofolate using NADPH
Why do we have to use thymidine nucleotides for DNA synthesis, rather than uracil?
Cytosine is unstable and undergoes spontaneous deamination to uracil. If uracil were in DNA, DNA repair mechanisms would be unable to distinguish between naturally occurring uracil and uracil arising
from the spontaneous deamination of cytosine. Hence, thymidine nucleotides are used in DNA
rather than uracil nucleotides.
What percentage of pyrimidines are recycled, and how does this compare to purines?
30% of pyrimidines are recycled compared to 90% in purines
At what level are pyrimidines recycled and how does this differ from purines?
pyrimidines are recycled at the level of nucleosides while purines are recycled as free bases
Do pyrimidine degradation products cause any pathologies? Why?
no, degradation products are highly water soluble and excreted in urine
How much energy is generated by pyrimidine catabolism?
none
Which nucleotide is an important target in cancer treatment?
thymidine (it is only found in DNA, its inhibition will inhibit replication)
What is AZT and what does it do?
a nucleoside, converted to AZT triphosphate in the body, inhibits DNA replication by competing with dTTP, also used in HIV treatment
What is 8-Azaguanine and what does it do?
in the purine salvage pathway, HGPRT catalyzes reaction that converts 8-Azaguanine into 8-Azaguanine triphosphate, which is incorporated into RNA and inhibits translation.