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Biosynthesis of Purine Nucleotide

S-2-Biochemistry
2 min read
Chemical Structure of purine
Chemical Structure of purine

De Novo Purine Synthesis Pathway

  • The de novo synthesis of purines starts with simple molecules like amino acids, carbon dioxide, and tetrahydrofolate.

  • The pathway is a stepwise construction of the purine ring attached to ribose-5-phosphate.

Here’s an outline of the main steps:

Formation of PRPP

  • Ribose-5-phosphate is converted to 5-phosphoribosyl-1-pyrophosphate (PRPP) by the enzyme PRPP synthetase.

  • Reaction: Ribose-5-phosphate + ATP → PRPP + AMP

Commitment Step

  • PRPP reacts with glutamine to form 5-phosphoribosylamine. This is catalyzed by amidophosphoribosyltransferase.

  • Reaction: PRPP + Glutamine → 5-Phosphoribosylamine + Glutamate + PPi

Formation of Inosine Monophosphate (IMP)

  • Through a series of steps involving the incorporation of atoms from glycine, formate (from N10-formyl-tetrahydrofolate), glutamine, aspartate, and CO₂, the molecule is converted into IMP.

  • Notable intermediates: Glycinamide ribonucleotide (GAR), Formylglycinamide ribonucleotide (FGAR), and 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR).

Conversion of IMP to AMP and GMP

  • AMP Pathway: IMP is converted to adenylosuccinate by adenylosuccinate synthetase, which then gets converted to AMP by adenylosuccinate lyase.

  • GMP Pathway: IMP is oxidized to xanthosine monophosphate (XMP) by IMP dehydrogenase and then converted to GMP-by-GMP synthetase.

Salvage Pathway of Nucleotide

  • The salvage pathway recycles free purine bases and nucleosides derived from the turnover of nucleic acids. Key enzymes involved include:

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

  • Converts hypoxanthine to IMP and guanine to GMP using PRPP.

Reactions:

  • Hypoxanthine + PRPP → IMP + PPi

  • Guanine + PRPP → GMP + PPi

Adenine phosphoribosyltransferase (APRT)

  • Converts adenine to AMP.

  • Reaction: Adenine + PRPP → AMP + PPi

Regulation

  • The biosynthesis of nucleotides is tightly regulated through feedback inhibition to ensure balance and meet cellular demands:

Purine Synthesis

  • Key regulatory points include inhibition of PRPP synthetase and amidophosphoribosyltransferase by end products (AMP, GMP).


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