title: Arginase in Leishmania.
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.
authors.affiliation: Departamento de Fisiologia - Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Maria Fernanda Laranjeira
authors.initials: MF
authors.lastname: da Silva
authors.forename: Lucile Maria
authors.initials: LM
authors.lastname: Floeter-Winter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001119:Arginase / Q000737:chemistry / Q000378:metabolism*; D007891:Leishmania / Q000201:enzymology*; D008969:Molecular Sequence Data; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D052247:Nitric Oxide Synthase Type II; D001119:Arginase