The synthesis of adenosine monophosphate (AMP) from inosine monophosphate (IMP) replaces a ketone with an amino group. GTP provides the phosphoryl group, and aspartate provides the amino group. The process occurs in two steps:

1. IMP, GTP, and aspartate react to form adenylosuccinate:
$$ \text{IMP} + \text{GTP} + \text{Aspartate} \rightarrow \text{Adenylosuccinate} + \text{GDP} + \text{P}_i $$
2. Adenylosuccinate is cleaved to yield adenylate (AMP) and fumarate:
$$ \text{Adenylosuccinate} \rightarrow \text{AMP} + \text{Fumarate} $$

Synthesis of Adenosine Monophosphate (AMP) from IMP

The synthesis of guanosine monophosphate (GMP) from inosine monophosphate (IMP) involves adding a ketone and then aminating it. The process occurs in two steps:

1. IMP is oxidized with NAD+ and H2O to form xanthylate:
$$ \text{IMP} + \text{H}_2\text{O} + \text{NAD}^+ \rightarrow \text{Xanthylate} + \text{NADH} + \text{H}^+ $$
2. Xanthylate reacts with ATP and ammonia (derived from the hydrolysis of glutamine) to produce guanylate (GMP) and glutamate.

Synthesis of Guanosine Monophosphate (GMP) from IMP

In the purine de novo synthesis pathway, inosine monophosphate (IMP, also known as inosinate) serves as a common intermediate for synthesizing adenosine monophosphate (AMP) and guanosine monophosphate (GMP). The conversion of IMP to either AMP or GMP involves aminating the molecule. To synthesize AMP, a ketone group is replaced with an amino group. To synthesize GMP, another ketone group is added and subsequently aminated.

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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

- 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



Overall control of purine synthesis (4 distinct regulations)


Synthesis of AMP and GMP from Inosine Monophosphate (IMP)

Phosphoribosylamine synthesis is the first committed and highly regulated step in the purine de novo synthesis pathway. In this reaction, the enzyme glutamine phosphoribosyl amidotransferase catalyzes the addition of ammonia to PRPP, producing 5-phosphoribosyl-1-amine and PPi. This enzyme is allosterically regulated and is inhibited by the downstream products AMP, ATP, GMP, and GTP.

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