Amino Acids

, Volume 40, Issue 2, pp 269–285 | Cite as

Polyamine metabolism in Leishmania: from arginine to trypanothione

  • Gianni ColottiEmail author
  • Andrea IlariEmail author
Review Article


Polyamines (PAs) are essential metabolites in eukaryotes, participating in a variety of proliferative processes, and in trypanosomatid protozoa play an additional role in the synthesis of the critical thiol trypanothione. The PAs are synthesized by a metabolic process which involves arginase (ARG), which catalyzes the enzymatic hydrolysis of l-arginine (l-Arg) to l-ornithine and urea, and ornithine decarboxylase (ODC), which catalyzes the enzymatic decarboxylation of l-ornithine in putrescine. The S-adenosylmethionine decarboxylase (AdoMetDC) catalyzes the irreversible decarboxylation of S-adenosylmethionine (AdoMet), generating the decarboxylated S-adenosylmethionine (dAdoMet), which is a substrate, together with putrescine, for spermidine synthase (SpdS). Leishmania parasites and all the other members of the trypanosomatid family depend on spermidine for growth and survival. They can synthesize PAs and polyamine precursors, and also scavenge them from the microenvironment, using specific transporters. In addition, Trypanosomatids have a unique thiol-based metabolism, in which trypanothione (N1-N8-bis(glutathionyl)spermidine, T(SH)2) and trypanothione reductase (TR) replace many of the antioxidant and metabolic functions of the glutathione/glutathione reductase (GR) and thioredoxin/thioredoxin reductase (TrxR) systems present in the host. Trypanothione synthetase (TryS) and TR are necessary for the protozoa survival. Consequently, enzymes involved in spermidine synthesis and its utilization, i.e. ARG, ODC, AdoMetDC, SpdS and, in particular, TryS and TR, are promising targets for drug development.


Polyamines Leishmania Arginine Trypanothione Redox metabolism Drug targets 





S-Adenosylmethionine decarboxylase




Amino acid-polyamine-organocation


Ascorbate peroxidase




Cationic amino acid transporter


Decarboxylated S-adenosylmethionine




Eukaryotic translation elongation factor 1B


Glutathione reductase


Glutathionyl-spermidine synthetase




Mitochondrial carrier family


Nitric oxide


Nitric oxide synthase


Non selenium glutathione peroxidase-like enzyme


Ornithine decarboxylase




Polyamine oxidase


Pyridoxal 5′-phosphate


Parasitophorous vacuole


Reactive oxygen species


Reactive nitric oxide species


Ribonucleotide reductase




Spermidine synthase




Tryparedoxin peroxidase


Trypanothione reductase


Thioredoxin reductase


Trypanothione synthetase


Trypanothione, or N1, N8-bis(glutathionyl)spermidine




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© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Institute of Biology and Molecular Pathology, CNR, c/o Department of Biochemical SciencesUniversity “Sapienza”RomeItaly

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