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Girard 2018 mSphere
Additional label Labels  + , 2018-08  +
Coupling states LEAK  + , ET  +
Has abstract Amino acids participate in several critica
Amino acids participate in several critical processes in the biology of trypanosomatids, such as osmoregulation, cell differentiation, and host cell invasion. Some of them provide reducing power for mitochondrial ATP synthesis. It was previously shown that alanine, which is formed mainly by the amination of pyruvate, is a metabolic end product formed when parasites are replicating in a medium rich in glucose and amino acids. It was shown as well that this amino acid can also be used for the regulation of cell volume and resistance to osmotic stress. In this work, we demonstrate that, despite it being an end product of its metabolism, ''Trypanosoma cruzi'' can take up and metabolize l-Ala through a low-specificity nonstereoselective active transport system. The uptake was dependent on the temperature in the range between 10 and 40°C, which allowed us to calculate an activation energy of 66.4 kJ/mol and estimate the number of transporters per cell at ~436,000. We show as well that, once taken up by the cells, l-Ala can be completely oxidized to CO<sub>2</sub>, supplying electrons to the electron transport chain, maintaining the electrochemical proton gradient across the mitochondrial inner membrane, and supporting ATP synthesis in ''T. cruzi'' epimastigotes. Our data demonstrate a dual role for Ala in the parasite's bioenergetics, by being a secreted end product of glucose catabolism and taken up as nutrient for oxidative mitochondrial metabolism. It is well known that trypanosomatids such as the etiological agent of Chagas' disease, ''Trypanosoma cruzi'', produce alanine as a main end product of their energy metabolism when they grow in a medium containing glucose and amino acids. In this work, we investigated if under starvation conditions (which happen during the parasite life cycle) the secreted alanine could be recovered from the extracellular medium and used as an energy source. Herein we show that indeed, in parasites submitted to metabolic stress, this metabolite can be taken up and used as an energy source for ATP synthesis, allowing the parasite to extend its survival under starvation conditions. The obtained results point to a dual role for Ala in the parasite's bioenergetics, by being a secreted end product of glucose catabolism and taken up as nutrient for oxidative mitochondrial metabolism.
nt for oxidative mitochondrial metabolism.  +
Has editor [[Plangger M]]  +
Has info [https://www.ncbi.nlm.nih.gov/pubmed/30021880 PMID: 30021880 - Open Access]  +
Has publicationkeywords Chagas disease  + , ''Trypanosoma cruzi''  + , Bioenergetics  + , L-alanine metabolism  + , L-alanine uptake  +
Has title Girard RMBM, Crispim M, Alencar MB, Silber AM (2018) Uptake of L-Alanine and its distinct roles in the bioenergetics of ''Trypanosoma cruzi''. mSphere pii:e00338-18.  +
Instrument and method Oxygraph-2k  +
Mammal and model Protists  +
MiP area Respiration  + , Exercise physiology;nutrition;life style  +
Preparation Intact cells  +
Respiration and regulation Amino acid  +
Was published by MiPNetLab BR Sao Paulo Silber AM +
Was published in journal MSphere +
Was published in year 2018  +
Was written by Girard RMBM + , Crispim M + , Alencar MB + , Silber AM +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
14:05:35, 30 August 2018  +
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