Overview Diagram Flashcards
How does IMP become DNA?
IMP is converted into AMP via adenylo-succinate synthetase + Adenylosuccinate lyase.
AMP is then converted into dATP and then DNA. (Fludarabine inhibits here).
IMP is also converted into XMP via IMP dehydrogenase (IMPDH).
XMP is converted into GMP via XMP-Gln-amino-transferase.
GMP into dGTP. Thio-GTP/Thio-dGTP inhibit here.
What does the enzyme IMP dehydrogenase (IMPDH) do?
What inhibits it? [3]
IMPDH converts IMP into XMP.
TAD, from Tiazofurin inhibits this via NAD-binding site.
Thio-IMP, from 6-MP, inhibits this (as well as adenylosuccinate).
Thio-GMP, from 6-TG, inhibits this.
Both Thio-IMP and Thio-GMP inhibit it via the purine binding site.
What does the enzyme Adenylosuccinate synthetase do?
What inhibits this? [1]
It, alongside adenylo-succinate lyase, converts IMP into AMP.
It is inhibited by Thio-IMP, from 6-MP. (this also inhibits IMPDH, which normally converts IMP into XMP)
What does HPRT do?
It converts both 6-MP into Thio-IMP and also
6-TG into Thio- GMP.
Thio-IMP and Thio-GMP then go on to inhibit IMPDH preventing the formation of XMP from IMP.
What does XMP-Gln-amino-transferase do?
XMP into GMP for DNA synthesis.
What is the enzyme CTP synthase?
What inhibits it? [1]
UTP is converted into CTP via CTP synthase.
CTP synthase in inhibited by F2dCDP.
F2dCDP also inhibits ribonuclease reductase.
What does the enzyme ribonuclease reductase do?
What inhibits it? [1]
It converts CTP into dCTP.
It is inhibited by F2dCDP - covalent binding to active site.
What does the enzyme dCK do?
What inhibits this?
dCK is responsible for converting Gemcitabine (F2dC) into f2dCMP.
dCK is inhibited by dCTP.
This is how gemcitabine self-potentiates itself, it inhibits dCTP.
What is the purpose of UMP/CMP kinase?
What does its conversion product inhibit? [2]
Converts f2dCMP into F2dCDP.
F2dCDP can then inhibit both CTP synthase (preventing UTP -> CTP) and ribnuclease reductase (preventing CTP -> dCTP).
What is NDP kinase?
What does its conversion product inhibit?
Converts F2dCDP into F2dCTP.
F2dCTP inhibits, competitively, the incorporation of dCTP into DNA via DNA pol.
What does TS do?
What inhibits it? [6]
TS converts dUMP into dTMP via 5,10-tetra hydrofolate into dihydrofolate as part of the folate cycle.
TS is inhibited by:
F2dUMP from F2dCMP from Gemcitabine.
FdUMP from 5-FU
Pemetrexed, raltitrexed, plevitrexed, nolatrexed.
What is DHFR?
What inhibits it? [5]
DHFR converts dihydrofolate into tetrahydrofolate using NADPH -> NADP+.
DHFR is inhibited by:
Methotrexate
Lipophillic antifolates: pyrimethamine, methylbenzoprim, piritexim, nolatrexed.
What is SHMT?
Converts serine to glycine and tetra-hydrofolate to 5,10-tetra hydrofolate.
What is the purpose of deoxycytidine deaminase?
Converts F2dCMP into F2dUMP to inhibit TS.
