Purine Nucleotide Synthesis

Question 1

What are the 2 purines?

Answer 1

• Adenine
• Guanine

Question 2

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

Answer 2

• De novo pathway
• Salvaged pathway

Question 3

When does the de novo pathway synthesize purines?

Answer 3

During high nucleotide demand

Question 4

What is PRPP?

Answer 4

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

Question 5

BRIEFLY describe the de novo pathway?

Answer 5

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

Question 6

What are the building blocks for the de novo pathway?

Answer 6

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

Question 7

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

Answer 7

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

Question 8

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

Answer 8

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

Question 9

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

Answer 9

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

Question 10

How is purine synthesis regulated?

Answer 10

• 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 11

How are purines catabolized (broken down)?

Answer 11

• The final product of purine catabolism is uric acid that gets secreted from our bodies
• Hypoxanthine is oxidized to xanthine and then uric acid by xanthine oxidase

Question 12

Describe the catabolism of GMP to uric acid?

Answer 12

• Nucleotidase removes a phosphate from GMP to form Guanosine
• Nucleosidase removes ribose to form Guanine
• The amino group from guanine is removed to form xanthine which is then converted to uric acid by xanthine oxidase

Question 13

Describe gout

Answer 13

• Caused by elevated levels of uric acids
• Joints become inflamed and arthritic
• Occurs predominantly in males
• Treated by allopurinol which inhibits xanthine oxidase (resulting in the accumulation of xanthine)