Nucleotide Metabolism

Question 1

what is the effect of imbalance in nucleotides?

Answer 1

hampers nucleic acid synthesis and can cause genome instability

Question 2

energy from — drives many biochemical reactions

Answer 2

hydrolysis of NTPs (like ATP and GTP)

Question 3

NTP amounts are needed…

Answer 3

relatively (not necessaeily equal amounts

Question 4

what are NTPs targetted for? why?

Answer 4

anti-cancer therapies; cancer cells require a lot of NTPs -> disrupt nucleotide metabolism -> slow cell growth

Question 5

NTPs –>
dNTPs –>

Answer 5

RNA
DNA

Question 6

how does purine synthesis occur?

Answer 6

1. ribose-5-phosphate (from PPP)
2. phosphorylated into PRPP
3. then make phosphoribosyl-B-1-amine
4. (many steps) makes Inosine Monophosphate
   4.IMP makes either adenylosuccinate (ends up with ATP) or XMP (ends up with GTP)

Question 7

an important step of ATp making is

Answer 7

the use of ATP synthase in mitochondria in OxPhos

Question 8

how is purine synthesis regulated?

Answer 8

look at diagram

Question 9

how is pyrimidine synthesis occur?

Answer 9

orotate made first then added to PRPP

Question 10

how is orotate made?

Answer 10

HCO3- + glutamine + H2O + ATP -> carbamoyl phosphate

carbamoyl phosphate + asparate -> orotate

look at diagram

Question 11

what enzyme makes dNTPs?

Answer 11

ribonucleotide reductase (RNR)

Question 12

how does RNR work?

Answer 12

• electrons come from NADPH
• reduces any NDP to dNDP
• NTP -> NDP -> dNDP
• dNDPs are then phosphorylated to dNTPs

removes OH to H (H- -> OH-)

Question 13

what are the components of RNR?

Answer 13

• activity site: balance NDPs vs dNDPs (where ATP binds)
• specificity site: balaces dDNPs relative to each other (where dNDPs bind)