title: The active transport of histidine and its role in ATP production in Trypanosoma cruzi.
abstract: Trypanosoma cruzi, the aetiological agent of Chagas's disease, metabolizes glucose, and after its exhaustion, degrades amino acids as energy source. Here, we investigate histidine uptake and its participation in energy metabolism. No putative genes for the histidine biosynthetic pathway have been identified in genome databases of T. cruzi, suggesting that its uptake from extracellular medium is a requirement for the viability of the parasite. From this assumption, we characterized the uptake of histidine in T. cruzi, showing that this amino acid is incorporated through a single and saturable active system. We also show that histidine can be completely oxidised to CO2. This finding, together with the fact that genes encoding the putative enzymes for the histidine - glutamate degradation pathway were annotated, led us to infer its participation in the energy metabolism of the parasite. Here, we show that His is capable of restoring cell viability after long-term starvation. We confirm that as an energy source, His provides electrons to the electron transport chain, maintaining mitochondrial inner membrane potential and O2 consumption in a very efficient manner. Additionally, ATP biosynthesis from oxidative phosphorylation was found when His was the only oxidisable metabolite present, showing that this amino acid is involved in bioenergetics and parasite persistence within its invertebrate host.
authors.affiliation: Laboratory of Biochemistry of Tryps - LaBTryps, Departament of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Prédio Biomédicas II, Av. Lineu Prestes 1374, Sala 24, Cidade Universitária, (05508-000), São Paulo (SP), Brasil.
authors.forename: M J
authors.initials: MJ
authors.lastname: Barisón
authors.affiliation: Laboratory of Biochemistry of Tryps - LaBTryps, Departament of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Prédio Biomédicas II, Av. Lineu Prestes 1374, Sala 24, Cidade Universitária, (05508-000), São Paulo (SP), Brasil.
authors.forename: F S
authors.initials: FS
authors.lastname: Damasceno
authors.affiliation: Laboratory of Biochemistry of Tryps - LaBTryps, Departament of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Prédio Biomédicas II, Av. Lineu Prestes 1374, Sala 24, Cidade Universitária, (05508-000), São Paulo (SP), Brasil.
authors.forename: B S
authors.initials: BS
authors.lastname: Mantilla
authors.affiliation: Laboratory of Biochemistry of Tryps - LaBTryps, Departament of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Prédio Biomédicas II, Av. Lineu Prestes 1374, Sala 24, Cidade Universitária, (05508-000), São Paulo (SP), Brasil. asilber@usp.br.
authors.forename: A M
authors.initials: AM
authors.lastname: Silber
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D001693:Biological Transport, Active; D004579:Electron Transport; D004734:Energy Metabolism; D006639:Histidine / Q000378:metabolism* / Q000502:physiology; D010085:Oxidative Phosphorylation; D015800:Protozoan Proteins / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D006639:Histidine; D000255:Adenosine Triphosphate
keywords: ATP synthesis; Histidine oxidation; Histidine uptake; Trypanosoma cruzi bioenergetics; Trypanosomes metabolism