Nucleotide Metabolism Flashcards
what is the effect of imbalance in nucleotides?
affects nucleic acid synthesis and can cause genome instability
energy from — drives many biochemical reactions
hydrolysis of NTPs (like ATP and GTP)
NTP amounts are needed…
relatively (not necessaeily equal amounts
what are NTPs targetted for? why?
anti-cancer therapies; cancer cells require a lot of NTPs -> disrupt nucleotide metabolism -> slow cell growth
NTPs –>
dNTPs –>
RNA
DNA
how does RNA (NTP) purine synthesis occur?
- ribose-5-phosphate (from PPP)
- add pyrophosphate into PRPP
- make phosphoribosyl-B-1-amine
- (many steps) makes Inosine Monophosphate
4.IMP makes either adenylosuccinate (ends up with ATP) or XMP (ends up with GTP)
an important step of ATP making is
the use of ATP synthase in mitochondria in OxPhos
how is purine (RNA) synthesis regulated?
ATP is made with GTP-> GDP hydrolysis
GTP is made with ATP-> ADP-> AMP hydrolysis
how is pyrimidine (RNA, NTP) synthesis occur?
Energy from?
orotate (ring) made first then added to PRPP
-> OMP -> UMP -> UDP -> UTP -> CTP
Uses ATP for energy
how is orotate made?
HCO3- + glutamine + H2O + ATP -> carbamoyl phosphate
carbamoyl phosphate + asparate -> orotate
look at diagram
RNA
What inhibits pyrimidine synthesis? What activates pyrimidine synthesis?
IN RNA (NTPS)
inhibits: UDP and UTP
activates: ATP and PRPP
what enzyme makes dNTPs?
how does it do it?
ribonucleotide reductase (RNR)
reduce any NDP to dNPs
how does RNR work?
- electrons come from NADPH
- NTP -> NDP -> dNDP
- dNDPs are then phosphorylated to dNTPs
removes OH to H (H- -> OH-)
what are the components of RNR?
2 regulatory sites
- activity site: balance NDPs vs dNDPs (where ATP or dATP binds)
- specificity site: balances dNTPs relative to each other (where dNDPs bind)
active site (where NDPs bind)
What is an important step of dTTP synthesis?
- nonspecific nucleotide kinase phosphorylates dUDP to dUTP but this is quickly dephosed to dUMP
- DNAP doesn’t distinguish between dUTP and dTTP
