Tornheim NTs Flashcards
Nucleotide combination
Base + Ribose + Phosphates
Uracil
Base, Nucleoside, NT?
Uracil, Uridine, Uridylate (-ic acid)
Cytosine
Base, Nucleoside, NT?
Cytosine, Cytidine, Cytidylate
Hypoxanthine
Base, Nucleoside, NT?
Hypoxanthine, Inosine, Inosinate
Xanthine
Base, Nucleoside, NT?
Xanthine, Xanthosine, Xanthylate
PRPP Synthetase Inhibitors
4 products: IMP, AMP, GMP, GDP
and ADP
- basically inhibited by products
PRPP Aminotransferase Inhibitors
4 products: IMP, AMP, GMP, GDP
and ADP, ATP, GTP
- basically inhibited by products
Adenylosuccinate Synthetase Inhibitor
AMP
IMP DH Inhibitor
GMP
Describe the purine salvage pathways
1) Hypoxanthine or Guanine to IMP or GMP
2) Adenine to AMP
What does Ribonucleotide Reductase do?
rDNP to dDNP
What does the first site of ribonucleotide reductase do?
Binding of dATP inhibits the enzyme
What does the second site of ribonucleotide reductase do?
- Binding of dATP/ATP causes reduction of UDP and GDP
- dTTP reduction of GDP, inhibits UDP, CDP
- dGTP reduction of ADP
Dihydrofolate Reductase Inhibitors
Aminopterin, Amethopterin (Methotrexate)
- these are folate analogs
What is special about dTMP
It is only used in DNA, so its a good target for chemotherapy
Absence of HGPRT causes
Lesch-Nyhan Syndrome
- symptoms: gout, self-mutilation, intellectual disability
3 ways that chemotherapy works
1) Blocks NT biosynthesis
2) Kills proliferating cells
3) Blocks DNA replication (NT analogues)
Folate antagonists (Methotrexate) mechanism
Kill proliferating cells
Fluorouracil, Fluorodeoxyuridine mechanism
Block NT biosynthesis
AraC, AraA, 5-iododeoxyuridine mechanism
Inhibit chain elongation as NT analogues
- arabinose analogue of deoxycytosine and deoxyadenine
- araA is a more potent inhibitor of viral polymerase vs the host polymerase
Acyclovir, Gancyclovir, AZT mechanism of action
Nucleoside analogues which act as chain terminators
- lack 3’ OH group
Why can Acyclovir, Gancylovir and 5-iododeoxyuridine be used to treat HPV?
They are activated via phosphorylation by the viral kinase, providing for selectivity
Which drugs are used to treat viral encephalitis?
araA
- more potent inhibitor of viral polymerase vs host polymerase
Which drugs are used to treat AIDS
AZT, dideoxy C and I