Intro + Purine Synthesis

Question 1

What are the roles of nucleotides in the cell?

Answer 1

1. DNA & RNA precursors.
2. Secondary Messenger (cAMP, cGMP)
3. Energy source (ATP, GTP)
4. Components of Coenzymes.
5. Component of biosynthetic intermediates

Question 2

Why am I studying these pathways?

Answer 2

Because you can target key steps in those pathways to design drugs for cancer and viral infections.

Question 3

What are the two pathways to synthesize nucleotides?

Answer 3

De novo & Salvage.

Question 4

What are the precursors of de novo synthesis?

Answer 4

Ammonia (NH3) and CO2.
Amino-acids and ribose-5-phosphate.

Question 5

What are the precursors in the Salvage pathway?

Answer 5

Nucleosides and bases from the break down of Nucleic Acids!

Question 6

What is the main difference between Pyrimidine and Purine de novo synthesis?

Answer 6

The precursor aminoacids.

Question 7

What do pyrimidine and purine de novo have in common?

Answer 7

PRPP=
Phosphoribosyl pyrophosphate

Question 8

What do I need to remember?

Answer 8

The structure and numbers of each atom + which amino acid was the precursor.

Question 9

What amino-acid gives its whole backbone in purine denovo synthesis?

Answer 9

Glycine: C4-C5-N7

Question 10

What amino acids give their amine in Purine denovo synthesis.

Answer 10

Aspartate: N1
Glutamine N3, N9

Question 11

How is PRPP made?

Answer 11

Ribose 5 Phosphate + ATP = Phosphoribosyl Pyrophosphate + AMP

Question 12

How does purine and pyrimidine de novo differ in the way they use PRPP?

Answer 12

The purine rings are assembled on PRPP. In Pyrimidines it is used later.

Question 13

What do important cancer therapies target in purine synthesis?

Answer 13

N10 formyl- tetra hydro folate.

Question 14

What is the first nucleotide synthesized in purine denovo?

Answer 14

IMP = Inosinate

Question 15

Draw a purine structure with the source of each atom and its number

Question 16

What is the order of reactions in Denovo synthesis of purines?

Answer 16

1. Ribose 5 Phosphate + ATP = PRPP + AMP
2. add N9 from glutamine (Transamidation)
3. Add Glycine backbone C4-C5-N7
4. Add C8 from 10N Formyl H4 Folate (Transformylation)
5. Add glutamine N3 (Amine Transfer)
6. ATP to close the first ring.
7. We’re adding CO2 for C6 ( Might be below first if you’re a lower organism).
8. Add aspartate for N1 (full backbone first)
9. C2 is given by Formate.
10. The second ring is closed by condensation and a water molecule is released!

Question 17

How is IMP (Inosinate) transformed into AMP?

Answer 17

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

Question 18

How is IMP Transformed into GMP?

Answer 18

Using NADH + H2O to put a ==O on C2. Then Glutamine and ATP. to put an NH2

Question 19

Summary of the differences between GMP and AMP synthesis:

Answer 19

GMP: we are using ATP + Glutamine.

AMP: we are using GTP + Aspartate