Polyamine metabolism in Leishmania: from arginine to trypanothione (Articolo in rivista)

  • Polyamine metabolism in Leishmania: from arginine to trypanothione (Articolo in rivista) (literal)
  • 2011-01-01T00:00:00+01:00 (literal)
  • 10.1007/s00726-010-0630-3 (literal)
Alternative label
  • Colotti G; Ilari A. (2011)
    Polyamine metabolism in Leishmania: from arginine to trypanothione
    in Amino acids (Wien, Print)
  • Colotti G; Ilari A. (literal)
Pagina inizio
  • 269 (literal)
Pagina fine
  • 285 (literal)
  • 40 (literal)
  • 2 (literal)
  • ISI Web of Science (WOS) (literal)
  • 1. Univ Roma La Sapienza, CNR, Inst Biol & Mol Pathol, Dept Biochem Sci, I-00185 Rome, Italy (literal)
  • Polyamine metabolism in Leishmania: from arginine to trypanothione (literal)
  • 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. (literal)
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