Question

What are the steps from cells and serine to purine nucleotides?

Answer 1

Synthesis of purine starts by activating ribose PRPP with the sequential addition of nitrogen and carbon containining units which is donated from glutamine (N), glycine (N&C), aspartate (N), folic acid (C1), or CO2.

1. Glutamine donates an NH2 group by the displacement of pyrophosphate at ribose C1. The carboxyl group binds with the amine bond to the NH2.
2. A one-carbon unit from folic acid coenzyme N10-formyl-THF is added to the amino group of the substituted glycine followed by the closure of the imidazole ring.
3. Second NH2 group is glutamine is transferred to the first carbon of the glycine unit
4. A carboxylation of the second carbon of the glycin unit is added.
5. new carbon is transferred from an aspartate residue which is modified by the third NH2 unit.
6. second one-carbon unit from formyl-THF is added to the nitrogen group and the ring covalently closed to form the common purine precursor inosine monophosphate.

The major source of carbon units for nucleic acid synthesis gets from serine. In this reaction, serine is converted to glycine, while one methylene group is covalently linked to THF to form 5,10-methylene-tetrahydrofolate. This reaction is catalyzed by a mitochondrial enzyme. Inosine monophosphate is converted to adenosine monophosphate by the following two steps.

First, GTP hydrolysis triggers the addition of aspartate to IMP by the help of an enzyme adenylosuccinate synthase, which acts as substitute for carbonyl oxygen of nitrogen and forming the intermediate adenylosuccinate. Fumarate is cleaved off forming adenosine monophosphate. This step is catalyzed by adenylosuccinate lyase. By oxidation of IMP, GMP is formed which results in the formation of xanthylate and the second step is followed by the insertion of an amino group at C2. NAD+ is the electron acceptor in the oxidation reaction. Glutamine is fueled by ATP hydrolysis as amide group is transfered.