Nucleotide Synthesis via Salvage Pathway

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.

Keywords: pathways; enzymes; human disorders

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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 References
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 Further Reading
    book Berg BO (ed.) (1996) Principles of Child Neurology. New York: McGraw-Hill.
    Murray AW, Elliott DC and Atkinson MR (1970) Nucleotide biosynthesis from preformed purines in mammalian cells: regulatory mechanisms and biological significance. Progress in Nucleic Acid Research and Molecular Biology 10: 87–119.
    book Neidhardt FC (1996) Escherichia coli and Salmonella. Cellular and Molecular Biology. Washington DC: ASM Press.
    book Nyhan WL and Ozand P (1998) Atlas of Metabolic Disease. London: Chapman & Hall.
    book Rosenberg RN, Prusiner ST, DiMauro S and Barchi RL (eds) (1996) The Molecular and Genetic Basis of Neurological Disease. Boston: Butterworth-Heinemann.
    book Scriver CR, Beaudet AL, Sly WS and Valle D (eds) (2001) The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill.
    Sinha SC and Smith JL (2001) The PRT protein family. Current Opinion in Structural Biology 11: 733–739.
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Nyhan, William L(Sep 2005) Nucleotide Synthesis via Salvage Pathway. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003909]