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Purine and Pyrimidine Metabolism in Leishmania

  • Chapter
Drug Targets in Kinetoplastid Parasites

Part of the book series: Advances In Experimental Medicine And Biology ((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.

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Author notes

  1. Buddy Ullman

    Present address: Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd Portland, Oregon, 97239-3098, USA

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, Oregon, USA

    Nicola S. Carter, Phillip Yates, Cassandra S. Arendt, Jan M. Boitz & Buddy Ullman

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  1. Nicola S. Carter
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  2. Phillip Yates
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  3. Cassandra S. Arendt
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  4. Jan M. Boitz
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  1. Molecular Parasitology Laboratory, Indian Institute of Chemical Biology, Kolkata, India

    Hemanta K. Majumder

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Carter, N.S., Yates, P., Arendt, C.S., Boitz, J.M., Ullman, B. (2008). Purine and Pyrimidine Metabolism in Leishmania . In: Majumder, H.K. (eds) Drug Targets in Kinetoplastid Parasites. Advances In Experimental Medicine And Biology, vol 625. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77570-8_12

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