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39 Cards in this Set

  • Front
  • Back
Purines?
adenine
guanine
hypoxanthine
xanthine
Pyrimidines?
cytosine
uracil
thymine
orotic acid
What is hypoxanthine's nucleoside?
inosine
Functions of nucleotides?
DNA and RNA polymer precursors
structural moieties of coenzymes
energy metabolism
ingredients of active metabolic precursors
physiological mediators
allosteric effectors of many metabolic enzymes
Four coenzymes that use a nucleotide as a structural moiety?
NADH
FAD
CoA
tetrahydrobiopterin
How are dietary nucleotides converted to nucleosides?
alkaline phosphatase
How many ATPs are used in the synthesis of purine and pyrimidine?
each use 6 ATP but purine does it in 11 steps while pyrimidine gets it done in 9
What is defective in gout?
de novo purine synthesis (g like guanine is a purine)
What is defective in Lesch-Nyhan syndrome?
purine salvage
Defect in orotic aciduria?
de novo pyrimidine synthesis
Where does ribose 5-phosphate come from?
glucose 6-phosphate via pentose phosphate pathway
or ribose 1-phosphate by nucleoside phosphorolysis
How is PRPP synthesized?
ribose 5-phosphate + ATP with PRPP synthetase
Which reactions and pathways require PRPP?
de novo synthesis and salvage purine AND pyrimidine pathways
NAD synthesis
What is the first committed step in purine synthesis?
Glutamine phosphoribosyl amidotransferase catalyzed conversion of PRPP + glutamine ->phosphoribosylamine
Which enzyme is defective in Lesch-Nyhan?
HGPRTase
What does allopurinol inhibit?
xanthine oxidase conversion of hypoxanthine to xanthine and xanthine to uric acid
Where are all the enzymes for purine de novo synthesis found within the cell?
cytosol
How are deoxyribonucleotides formed?
reduction of ribonucleoside 5'-diphosphates by ribonucleotide reductase
What acts as a cofactor in the synthesis of deoxyribonucleotides?
thioredoxin or glutaredoxin cofactors that help reduce ribose to deoxyribose
What role does NADPH play in deoxyribonucleotide synthesis?
reduces ribonucleotide reductase back to active form since it is oxidized in synthesis reaction
What are the different classes of chemotherapeutic agents?
antimetabolites
antifolates
glutamine antagonists
other compounds
antiviral agents
How do antimetabolites act?
structural analogs of bases or nucleosides so they interfere with specific sites of metabolism
What are three antimetabolites?
6-mercaptopurine
5-fluorouracil
cytosine arabinoside (araC)
6-mercaptopurine?
leukemia antitumor drug
purine analog that negatively effects PRPP amidotransferase of purine synthesis and neg effect on enzymes that make AMP and GMP from IMP
5-fluorouracil?
antitumor drug - pyrimidine analog
FUTP incorporates into RNA and stops maturation of 28S and 18S rRNA; and stops splicing of pre-mRNA
FdUMP inhibits thymidylate synthase
cytosine arabinose?
anti-leukemia cytidine analog
araCTP competes with dCTP in DNA polymerase reaction and when placed in DNA inhibits growth of strand
What are antifolates?
methotrexate (mtx)
inhibit formation of tetrahydrofolate by inhibiting dihydrofolate reductase
Methotrexate?
antitumor leukemia treatment; folate analog
inhibits dihydrofolate reductase thus depleting thymidine and purine nucleotides
Which reactions do glutamine antagonists effect?
amidation reactions using glutamine:
-de novo purine synthesis (N3 & N9)
-GMP synthesis from IMP
-cytosolic carbamoyl phosphate formation for pyrimidine synthesis
-CTP syntheis from UTP
-NAD synthesis
Azaserine and 6-diazo-5-oxo-norleucine (DON)?
antitumor glutamine analogs
inhibit enzymes that use glutamine as substrate
too toxic for clinical use
cytosine arabinose?
anti-leukemia cytidine analog
araCTP competes with dCTP in DNA polymerase reaction and when placed in DNA inhibits growth of strand
What are antifolates?
methotrexate (mtx)
inhibit formation of tetrahydrofolate by inhibiting dihydrofolate reductase
Methotrexate?
antitumor leukemia treatment; folate analog
inhibits dihydrofolate reductase thus depleting thymidine and purine nucleotides
Which reactions do glutamine antagonists effect?
amidation reactions using glutamine:
-de novo purine synthesis (N3 & N9)
-GMP synthesis from IMP
-cytosolic carbamoyl phosphate formation for pyrimidine synthesis
-CTP syntheis from UTP
-NAD synthesis
Azaserine and 6-diazo-5-oxo-norleucine (DON)?
antitumor glutamine analogs
inhibit enzymes that use glutamine as substrate
too toxic for clinical use
Hydroxyurea?
not an analog but inhibits ribonucleotide reductase to inhibit DNA synthesis but not RNA
Tiazofurin?
not an analog, has a ribose unit
inhibits IMP dehydrogenase, the limiting step in GTP synthesis
Acyclovir (acycloguanosine)?
antiviral against Herpes HSV
a purine base coupled with sugar analog
its triphosphate form is substrate for HSV-specific DNA polymerase so it stops DNA chain growth
3'-azido-2'-deoxythymidine (AZT)?
thymidine analog used against HIV
inhibits HIV-DNA polymerase which is RNA dependent
the host DNA polymerase is DNA dependent so much less sensitive