Intro + Purine Synthesis Flashcards
What are the roles of nucleotides in the cell?
- DNA & RNA precursors.
- Secondary Messenger (cAMP, cGMP)
- Energy source (ATP, GTP)
- Components of Coenzymes.
- Component of biosynthetic intermediates
Why am I studying these pathways?
Because you can target key steps in those pathways to design drugs for cancer and viral infections.
What are the two pathways to synthesize nucleotides?
De novo & Salvage.
What are the precursors of de novo synthesis?
Ammonia (NH3) and CO2.
Amino-acids and ribose-5-phosphate.
What are the precursors in the Salvage pathway?
Nucleosides and bases from the break down of Nucleic Acids!
What is the main difference between Pyrimidine and Purine de novo synthesis?
The precursor aminoacids.
What do pyrimidine and purine de novo have in common?
PRPP=
Phosphoribosyl pyrophosphate
What do I need to remember?
The structure and numbers of each atom + which amino acid was the precursor.
What amino-acid gives its whole backbone in purine denovo synthesis?
Glycine: C4-C5-N7
What amino acids give their amine in Purine denovo synthesis.
Aspartate: N1
Glutamine N3, N9
How is PRPP made?
Ribose 5 Phosphate + ATP = Phosphoribosyl Pyrophosphate + AMP
How does purine and pyrimidine de novo differ in the way they use PRPP?
The purine rings are assembled on PRPP. In Pyrimidines it is used later.
What do important cancer therapies target in purine synthesis?
N10 formyl- tetra hydro folate.
What is the first nucleotide synthesized in purine denovo?
IMP = Inosinate
Draw a purine structure with the source of each atom and its number
What is the order of reactions in Denovo synthesis of purines?
- Ribose 5 Phosphate + ATP = PRPP + AMP
- add N9 from glutamine (Transamidation)
- Add Glycine backbone C4-C5-N7
- Add C8 from 10N Formyl H4 Folate (Transformylation)
- Add glutamine N3 (Amine Transfer)
- ATP to close the first ring.
- We’re adding CO2 for C6 ( Might be below first if you’re a lower organism).
- Add aspartate for N1 (full backbone first)
- C2 is given by Formate.
- The second ring is closed by condensation and a water molecule is released!
How is IMP (Inosinate) transformed into AMP?
2 steps. we add Aspartate to C6 and then remove the rest of it’s backbone (Fumarate) leaving only the NH2. We use GTP.
Amine transfer
How is IMP Transformed into GMP?
Using NADH + H2O to put a ==O on C2. Then Glutamine and ATP. to put an NH2
Summary of the differences between GMP and AMP synthesis:
GMP: we are using ATP + Glutamine.
AMP: we are using GTP + Aspartate
