- PRPP is inhibited by IMP, AMP, GMP, GDP, and ADP
- IMP is inhibited by IMP, GMP, and AMP
- If you inhibit PRPP, you’re also going to inhibit the synthesis of histidine, and pyrimidine nucleotides
- AMP feeds back to inhibit synthesis of AMP
> Same for GMP

>Allows for both to catch up to each other



Michigan State University

SOURCES OF CARBON AND NITROGEN IN PURINES
- Amino acids: Nitrogen, glutamine, aspartate, glycine, carbons, serine, through N10-formyl THF
- CO2

BIG PICTURE
- We’re going to create an intermediate: IMP
- Then we can make ATP and GTP
> Reduced to purine deoxynucleotides
> dATP, dGTP

STEPS
- Phosphoribosylamine synthesis
- Phosphoribosylamine -> Inosinate and beyond

Purine De Novo Pathway

- Enzyme: Glutamine phosphoribosyl amidotransferase
> Regulated by downstream products (Allosteric)

> Inhibited by AMP and ATP

> Inhibited by GMP and GTP

- First committed step
- Addition of ammonia from glutamate to PRPP
> Highly regulated

- PRPP -> PPi + 5-phosphoribosyl-1-amine
- Next steps don’t matter as much


Phosphoribosylamine Synthesis


- Common intermediate in synthesizing AMP and GMP
- Also called inosine monophosphate IMP
- AMP: replace ketone with amino group
- GMP: add another ketone and aminate that
- In each case, we are aminating the molecule so we can add to it
- AMP
> Phosphate group: GTP

> Amino group: Aspartate

> Loss of fumarate

> End with Adenylate (AMP)

> IMP (inosinate) + GTP + Asp -> Adenylosuccinate + Pi + GDP

> Adenylosuccinate -> Fumarate and adenylate (AMP)

- GMP
> Phosphate group: ATP

> Amino group: Ammonia grom glutamine source

> Inosinate (IMP) + H2O + NAD+ -> NADH + H+ + Xanthylate

> Xanthylate + ATP  + Glu + H3N -> Guanylate (GMP)

> Glu and H3N are from Gln + H2O


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