Furthermore, Chagas’ disease is becoming an AZD1208 mw important health issue in the United States and Europe (Tarleton et al., 2007). During its life cycle, T. cruzi is exposed to different conditions in the insect gut, the mammalian

bloodstream and also cell cytoplasm, which required evolutionary adaptations to such environments (Brener, 1973; Kollien et al., 2001). Among them, transport processes are rapid and efficient mechanisms for supplying metabolites from parasite extracellular media, and also to regulate the first step on metabolic pathways. Trypanosomatids have a metabolism largely based on the consumption of amino acids, which constitute the main carbon and energy sources in the insect stage of the parasite life cycle (Silber et al., 2005). In T. cruzi, arginine is an essential amino acid and a key substrate for several metabolic pathways and it is obtained from the host through different transport systems or by intracellular proteolysis (Pereira et al., 1999; Canepa et al., 2004). Arginine participates in the management of cell energy through an arginine kinase (Pereira et al., 2000; Alonso et al., 2001). This enzyme, which was also found

in Trypanosoma brucei (Pereira et al., 2002b), catalyses the reversible transphosphorylation between phosphoarginine Fulvestrant cell line and ATP, and thus phosphorylated arginine acts as an energy reservoir involved in the renewal of ATP (Pereira et al., 2002a, 2003). As phosphoarginine is completely absent in mammalian tissues, arginine kinase is a possible target for the future development of chemotherapeutic agents. Despite the relevance selleck products of amino acids in trypanosomatids, the way in which they are internalized to become available for metabolism remains relatively unexplored. In this sense, the amino acid transporters are the first cell proteins that are in contact

with solutes in the surrounding medium, and in several cases they function not only as permeases to carry the solutes into the cytoplasm but also as environmental sensors. One of the major transporter families of amino acids is AAAP (TC 2.A.18), which is largely found in plants (Young et al., 1999). In T. cruzi, members of this family were first identified by our group (Bouvier et al., 2004) and confirmed by the Tritryps genome project (Berriman et al., 2005). The T. cruzi subfamily, named TcAAAP, has >30 genes coding for proteins with lengths of 400–500 amino acids and 10–12 predicted transmembrane α-helical spanners. One interesting feature of this permease family is the absence of similar sequences in mammalian organisms; however, the presence of unidentified orthologues could not be rejected (Akerman et al., 2004). In this work we present the first functional characterization of an amino acid permease from T. cruzi. TcAAAP411 was identified as a specific arginine permease and functionally characterized in a yeast model.