Purine Synthesis

Question 1

How does the de novo purine nucleotide synthesis pathway work?

Answer 1

Ribose 5 phosphate is converted to PRPP

Inosine-5-monophosphate (IMP) is generated by building a purine ring attached to the C-1 position of PRPP

IMP is the precursor for AMP and GMP

Question 2

How is AMP formed?

Answer 2

AMP differs from IMP by 1 functional group
Need nitrogen to convert IMP to AMP–source is aspartate
GTP is required

Question 3

How is GMP formed?

Answer 3

IMP differs from GMP by 1 functional group
Takes 2 reactions

1) IMP is oxidized to xanthosine monophosphate
2) XMP is converted to GMP using nitrogen from glutamine

ATP is required

Notice..ATP is required to make GMP and GTP is required to make AMP–provides a mechanism to balance synthesis of both

Question 4

How are NDP and NTP synthesized form NMP?

Answer 4

AMP + ATP -> 2 ADP

NMP + ATP -> NDP + ADP

Question 5

When does de novo synthesis occur?

Answer 5

When pools of products are low–feedback mechanism

Takes a lot of energy to produce de novo!

Question 6

What enzymes are involved in the salvage pathways?

Answer 6

Hypoxanthine-guanine phosphoribosyltransferase – HGPRT
- converts hypoxanthine and PRPP to IMP

and

Adenine phosphoribosyltransferase – APRT

Question 7

What is Lesch-Nyhan syndrome?

Answer 7

X linked
Symptoms–self mutilation, involuntary movements, mental retardation
Cause–excessive production of uric acid (degradation product of purine metabolism)
Basis–mutation in HGPRT–bases generated by nucleic acid breakdown cannot be recycled by the salvage pathway and are catabolized to create extra uric acid, which builds up

Question 8

What are the two nucleotide synthesis pathways?

Answer 8

De novo and salvasge