Nucleotide Synthesis via Salvage Pathway

Abstract The biosynthesis of purine and pyrimidine nucleotides takes place overde novosynthetic pathways from small molecules and by salvage pathways from preformed purine or pyrimidine bases or nucleosides. The pathways ofde novosynthesis are the same in animals and microorganisms. Salvage pathways are considerably more energy‐efficient thande novopathways, 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.