Purine and pyrimidine metabolism in Leishmania

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

Research output: Chapter in Book/Report/Conference proceedingChapter

67 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationDrug Targets in Kinetoplastid Parasites
PublisherSpringer New York
Pages141-154
Number of pages14
ISBN (Print)9780387775692
DOIs
StatePublished - Jan 1 2008

Publication series

NameAdvances in Experimental Medicine and Biology
Volume625
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Purine and pyrimidine metabolism in Leishmania'. Together they form a unique fingerprint.

  • Cite this

    Ullman, B., Carter, N. S., Yates, P., Arendt, C. S., & Boitz, J. M. (2008). Purine and pyrimidine metabolism in Leishmania. In Drug Targets in Kinetoplastid Parasites (pp. 141-154). (Advances in Experimental Medicine and Biology; Vol. 625). Springer New York. https://doi.org/10.1007/978-0-387-77570-8_12