Purine metabolism

Many organisms have metabolic pathways to synthesise and break down purines.

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Synthesis

Purines are biologically synthesized as nucleosides (bases attached to ribose). The committed step is amidophosphoribosyltransferase.

Both adenine and guanine are derived from the nucleoside inosine monophosphate (IMP), which is synthesised on a pre-existing ribose through a complex pathway using atoms from the amino acids glycine, glutamine, and aspartic acid, as well as formate ions transferred from the coenzyme tetrahydrofolate.

GMP

• IMP dehydrogenase converts IMP into XMP
• GMP synthase converts XMP into GMP
• GMP reductase converts GMP back into IMP

AMP

• adenylosuccinate synthase converts IMP to adenylosuccinate
• adenylosuccinate lyase converts adenylosuccinate into AMP
• AMP deaminase converts AMP back into IMP

Degradation

Purines from food (or from tissue turnover) are metabolised by several enzymes:

Guanine

• A nuclease frees the nucleotide
• A nucleotidase creates guanosine
• Purine nucleoside phosphorylase acts upon guanosine to create guanine
• Guanase acts upon guanine to create xanthine
• Xanthine oxidoreductase acts upon xanthine to create uric acid

Adenine

• A nuclease frees the nucleotide
  • In one path: a nucleotidase creates adenosine, and adenosine deaminase creates inosine (the deficiency of this enzyme is a cause of severe combined immunodeficiency)
  • In the other path: AMP deaminase creates IMP, and a nucleotidase creates inosine
• Purine nucleoside phosphorylase acts upon inosine to create hypoxanthine
• Xanthine oxidoreductase acts upon hypoxanthine to create xanthine
• Xanthine oxidoreductase acts upon xanthine to create uric acid

High levels of uric acid can predispose to gout when the acid crystalises in joints; this phenomenon only happens in humans and some animal species (e.g. dogs) that lack an intrinsic uricase enzyme that can further degrade uric acid into 5-Hydroxyisourate.

Salvage

Purines from turnover of nucleic acids (or from food) can also be salvaged and reused in new nucleotides.

• The enzyme adenine phosphoribosyltransferase (APRT) salvages adenine.
• The enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) salvages guanine and hypoxanthine. (Genetic deficiency of HPRT causes Lesch-Nyhan syndrome.)