Purine metabolism

Synthesis

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

Both 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 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 nucleotide
  • In one path: a nucleotidase 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 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 Lesch-Nyhan syndrome.)