Nucleotide Synthesis via Salvage Pathway

Abstract

The biosynthesis of purine and pyrimidine nucleotides takes place over de novo synthetic pathways from small molecules and by salvage pathways from preformed purine or pyrimidine bases or nucleosides. The pathways of de novo synthesis are the same in animals and microorganisms. Salvage pathways are considerably more energy‐efficient than de novo pathways, which require 5 (pyrimidine) or 6 (purine) moles of ATP for each mole of nucleotide produced. Salvage pathways are integral to the cause or treatment of a number of human diseases of purine or pyrimidine metabolism. Among disorders of purine metabolism, the Lesch–Nyhan disease is characterised by overproduction of uric acid, clinical gout, nephropathy, neurologic disease, and unusual self‐injurious behaviours.

Key Concepts:

  • Salvage of purines is catalysed by adenine phosphoribosyltransferase (APRT) and hypoxanthine guanine phosphoribosyltransferase (HGPRT).

  • Pyrimidine salvage is catalysed by thymidine kinase.

  • Pyrimidine salvage is effective in the treatment of orotic aciduria, a disorder of pyrimidine nucleotide synthesis.

  • Deficiency of APRT leads to renal calculi.

  • Deficiency of HGPRT is the cause of Lesch–Nyhan disease.

Keywords: pathways; enzymes; human disorders; purines; pyrimidines; adenine phosphoribosyltransferase (APRT); hypoxanthine guanine phosphoribosyltransferase (HGPRT)

Figure 1.

Pathways of mammalian purine nucleotide synthesis. The de novo pathway is shown schematically from the top as well as the central role of IMP in nucleotide interrelations. Salvage of purine bases is catalysed by hypoxanthine guanine phosphoribosyltransferase (HGPRT) and adenine phosphoribosyltransferase (APRT). Other abbreviations include: ASL, adenylosuccinate lyase; AMPDA, adenylate deaminase; ADA, adenosine deaminase; PNP, purine nucleoside phosphorylase; XO, xanthine oxidase; and PPi, inorganic pyrophosphate.

Figure 2.

Pathways of mammalian pyrimidine nucleotide synthesis. The de novo pathway is shown at the left. Among the salvage enzymatic pathways, uridine kinase catalyses the formation of CMP as well as UMP, while deoxycytidine kinase catalyses the synthesis of a dCMP and dUMP. Thymidine kinase is specific for the thymidine substrate.

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Nyhan, William L(Dec 2014) Nucleotide Synthesis via Salvage Pathway. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001399.pub3]