Purine Nucleotide Synthesis

Question 1

What are the 2 different ways that purines can be synthesized?

Answer 1

• De novo pathway
• Salvaged pathway

Question 2

When is the de novo pathway utilized to synthesize purines?

Answer 2

During high nucleotide demand

Question 3

What is PRPP?

Answer 3

A pentos sugar that is the precursor (foundation) for both the salvage and de novo pathways

Question 4

BRIEFLY describe the de novo pathway?

Answer 4

• 11 steps
• Roughly the same in all organisms
• Synthesizes new nitrogenous bases on top of PRPP (from scratch)
• Energy consuming process (ATP = use)

Question 5

What are the building blocks for the de novo pathway?

Answer 5

• Glycine
• Aspartate
• Glutamine
• Carbon atoms from CO2 or formate

Question 6

What is the rate limiting step in the de novo pathway?

Answer 6

Step 1: PRPP reacts with Gln
Catalyzed by glutamine PRPP amidotransferase

Question 7

Describe the synthesis of AMP and GMP from IMP (de novo pathway)

Answer 7

• IMP –> AMP = consumes GTP (nitrogen comes from aspartate)
• IMP —> GMP = consumes ATP (nitrogen comes from glutamine)

Question 8

How does the salvage pathway form AMP, GMP, and IMP?

Answer 8

-AMP:
Adenine + PRPP —> AMP
- GMP:
Guanine + PRPP —> GMP
- IMP:
Hypoxanthine —> IMP

Question 9

How is purine synthesis regulated?

Answer 9

• Rate limiting step = catalyzed by glutamine-PRPP amidotransferase
• This enzyme is inhibited by products that form downstream from the reaction (ex: IMP)
• This slows down the rate of the reaction preventing the formation of de novo synthesis of nucleotides

Question 10

How are purines catabolized (broken down)?

Answer 10

The final product of purine catabolism is uric acid that gets secreted from our bodies