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Purine and Pyrimidine Metabolism in Leishmania

  • Nicola S. Carter
  • Phillip Yates
  • Cassandra S. Arendt
  • Jan M. Boitz
  • Buddy Ullman
Part of the Advances In Experimental Medicine And Biology book series (AEMB, volume 625)

Abstract

Purines and pyrimidines are indispensable to all life, performing many vital functions for cells: ATP serves as the universal currency of cellular energy, cAMP and cGMP are key second messenger molecules, purine and pyrimidine nucleotides are precursors for activated forms of both carbohydrates and lipids, nucleotide derivatives of vitamins are essential cofactors in metabolic processes, and nucleoside triphosphates are the immediate precursors for DNA and RNA synthesis. Unlike their mammalian and insect hosts, Leishmania lack the metabolic machinery to make purine nudeotides de novo and must rely on their host for preformed purines. The obligatory nature of purine salvage offers, therefore, a plethora of potential targets for drug targeting, and the pathway has consequently been the focus of considerable scientific investigation. In contrast, Leishmania are prototrophic for pyrimidines and also express a small complement of pyrimidine salvage enzymes. Because the pyrimidine nucleotide biosynthetic pathways of Leishmania and humans are similar, pyrimidine metabolism in Leishmania has generally been considered less amenable to therapeutic manipulation than the purine salvage pathway. However, evidence garnered from a variety of parasitic protozoa suggests that the selective inhibition of pyrimidine biosynthetic enzymes offers a rational therapeutic paradigm. In this chapter, we present an overview of the purine and pyrimidine pathways in Leishmania, make comparisons to the equivalent pathways in their mammalian host, and explore how these pathways might be amenable to selective therapeutic targeting.

Keywords

Nucleoside Transporter Pyrimidine Metabolism Pyrimidine Biosynthesis Leishmania Donovani Equilibrative Nucleoside Transporter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  • Nicola S. Carter
    • 1
  • Phillip Yates
    • 1
  • Cassandra S. Arendt
    • 1
  • Jan M. Boitz
    • 1
  • Buddy Ullman
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyOregon Health & Science UniversityPortlandUSA

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