Characterization of Trypanosoma cruzi l-cysteine transport mechanisms and their adaptive regulation

Abstract

L-Cysteine and methionine are unique amino acids that act as sulfur donors in all organisms. In the specific case of Trypanosomatids, L-cysteine is particularly relevant as a substrate in the synthesis of trypanothione. Although it can be synthesized de novo, L-cysteine is actively transported in Trypanosoma cruzi epimastigote cells. L-Cysteine uptake is highly specific; none of the amino acids assayed yield significant differences in terms of transport rates. L-Cysteine is transported by epimastigote cells with a calculated apparent Km of 49.5 μM and a Vmax of about 13 pmol min−1 per 107 cells. This transport is finely regulated by amino acid starvation, extracellular pH, and between the parasite growth phases. In addition, L-cysteine is incorporated post-translationally into proteins, suggesting its role in iron–sulfur core formation. Finally, the metabolic fates of L-cysteine were predicted in silico.