Purine and pyrimidine metabolism in Leishmania

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

Research output: Contribution to journalArticle

61 Citations (Scopus)

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)
Pages (from-to)141-154
Number of pages14
JournalAdvances in Experimental Medicine and Biology
Volume625
DOIs
StatePublished - 2008

Fingerprint

Leishmania
Metabolism
Salvaging
Pyrimidine Nucleotides
Pyrimidines
Purines
Protozoa
Purine Nucleotides
Second Messenger Systems
Enzymes
Nucleosides
Vitamins
Machinery
Biosynthetic Pathways
RNA Precursors
Drug Delivery Systems
Nucleotides
Adenosine Triphosphate
Carbohydrates
RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Purine and pyrimidine metabolism in Leishmania. / Ullman, Buddy; Carter, Nicola; Yates, Phillip; Arendt, Cassandra S.; Boitz, Jan M.

In: Advances in Experimental Medicine and Biology, Vol. 625, 2008, p. 141-154.

Research output: Contribution to journalArticle

Ullman, Buddy ; Carter, Nicola ; Yates, Phillip ; Arendt, Cassandra S. ; Boitz, Jan M. / Purine and pyrimidine metabolism in Leishmania. In: Advances in Experimental Medicine and Biology. 2008 ; Vol. 625. pp. 141-154.
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