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27 Cards in this Set

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What are the three steps in Nucleotide triphosphate formation?
1. Formation of ATP
2. Formation of NDP
3. Formation of NTP
What is the enzyme responsible for ATP formation?
Adenylate kinase
What is the enzyme responsible for NDP formation?
NMP kinase
What is the enzyme responsible for NTP formation?
NDP kinase
What are the specificities associated with NDP kinases?
Bases specific. Non-specific for sugar.

e.g. - UMP kinase catalyzes UMP + ATP --> UDP + ADP
What are the specificities associated with UDP kinase?
Nonspecific for phosphate donor, base, and suar.

Very promiscuous.
What type of nucleotides are required for DNA synthesis?
deoxyribonucleotides
Purines and pyrimidines are synthesized as what?
ribonucleotides
What enzyme catalyzes the reduction of ribose to deoxyribose?
Ribonucleotide reductase
T/F - Ribonucleotide reductase acts on both nucleoside di- and triphosphates.
True
What are the subunits of ribonuceotide reductase?
R1 and R2
What are the two ways in which ribonucleotide reductase can be regulated?
1. Overall activity
2. Substrate specificity
What are the two regulatory sites of R1 in ribonucleotide reductase?
1. Primary regulation site controlling overall activity
2. Allosteric site controlling relative levels of each dNTP
In terms of ribonucleotide reductase overall activity, where does ATP bind and what effects does it have?
ATP binds at the primary regulation site on R1.

ATP activates formation of dADP, dCDP, dGDP, and dUDP
In terms of ribonucleotide reductase, where does dATP bind and what effects does it have?
dATP binds at the primary regulation site on R1.

dATP inhibits formation of dADP, dCDP, dGDP, and dUDP
In terms of ribonucleotide reductase overall activity, what two molecules are the activators/inhibitors?
ATP and dATP
In terms of ribonucleotide reductase substrate specificity, what does ATP do?
Increase UDP and CDP usage.
In terms of ribonucleotide reductase substrate specificity, what does dTTP do?
Increase GDP usage
In terms of ribonucleotide reductase substrate specificity, what does dGTP do?
Increase ADP usage.

Decrease GDP, UDP, and CDP usage.
T/F - Ribonucleotide reductase uses TDP.
False. Uses UDP instead.
What is an inhibitor of Ribonucleotide reductase?
Hydroxyurea
Which regulatory mechanism is responsible for ensuring equivalent levels of each dNTP made?
Substrate specificity site of ribonucleotide reductase
dTMP is synthesized from what two dNTP's?
dCTP or dUTP (after conversion to dUMP)
What prevents incorporation of uracil into DNA?
dUTPase
Describe the actions of thymidylate synthase to form dTMP.
Adds methyl group from THF to dUMP to form dTMP.
What is an inhibitor of thymidylate synthetase?
Fluorouracil
Thymidylate synthesis is also inhibited by what inhibitors of DHFR?
Methotrexate and sulfa drugs.