Arginase in Leishmania
The presence of different sets of several enzymes that participate in the Krebs-Henseleit cycle has been used to identify several genera of trypanosomatids. One of these enzymes is arginase (L-arginine amidinohydrolase, E.C. 3.5.3.1), a metalloenzyme that
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Arginase in Leishmania Maria Fernanda Laranjeira da Silva and Lucile Maria Floeter-Winter
Abstract The presence of different sets of several enzymes that participate in the Krebs-Henseleit cycle has been used to identify several genera of trypanosomatids. One of these enzymes is arginase (L-arginine amidinohydrolase, E.C. 3.5.3.1), a metalloenzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. Arginase activity has been detected in Leishmania, Crithidia and Leptomonas but not in Trypanosoma, Herpetomonas or Phytomonas. The ureotelic behavior of some trypanosomatids is not due to urea excretion but to the production of ornithine to supply the polyamine pathway, which is essential for replication. Leishmania is found inside macrophages in the mammalian host and to live in these cells, the parasite must escape from several microbicidal mechanisms, such as nitric oxide (NO) production mediated by inducible nitric oxide synthase (iNOS). Since arginase and iNOS use the L-arginine as substrate, the amount of this amino acid available for both pathways is critical for parasite replication. In both promastigotes and amastigotes, arginase is located in the glycosome indicating that arginine trafficking in the cell is used to provide the optimal concentration of substrate for arginase. Arginine uptake by the parasite is also important in supplying the arginase substrate. Leishmania responds to arginine starvation by increasing the amino acid uptake. In addition to the external supply, the internal L-arginine pool also governs the uptake of this amino acid, and the size of this internal pool is modulated by arginase activity. Thus, arginine uptake and arginase activity are important in establishing and maintaining Leishmania infection.
M.F.L. da Silva • L.M. Floeter-Winter (*) Departamento de Fisiologia – Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil e-mail: [email protected] A.L.S. Santos et al. (eds.), Proteins and Proteomics of Leishmania and Trypanosoma, Subcellular Biochemistry 74, DOI 10.1007/978-94-007-7305-9_4, © Springer Science+Business Media Dordrecht 2014
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M.F.L. da Silva and L.M. Floeter-Winter
Abbreviations AD AGM ARG ASL ASS CAT CH CPS1 EGFP eNOS IFNγ IL iNOS LOHA LPG nNOS NO OCT ORF PEX PST1 PV SSU rRNA UTR
1
Arginine deiminase Agmatinase Arginase Argininosuccinate lyase Argininosuccinate synthetase Cationic amino acid transporter Citrulline hydrolase Carbamoyl phosphate synthetase Enhanced green fluorescent protein Endothelial nitric oxide synthase Interferon gamma Interleukin Inducible nitric oxide synthase Nω-hydroxy-L-arginine Lipophosphoglycan Neuronal nitric oxide synthase Nitric oxide Ornithine carbamoyltransferase Open reading frame Peroxin Peroxisomal targeting signal type 1 Parasitophorous vacuole Small subunit ribosomal RNA Untranslated region
The Arginase Pathway
L-Arginine is one of the most versatile amino acids. It is used as a precursor not only for protein synthesis but also for the synthesis of NO, urea, ornithine, citrulline, cre
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