Proposed scheme of glucose metabolism of <i>T</i>. <i>cruzi</i> epimastigotes stimulated by heme.

T. cruzi epimastigotes increase proliferation and upregulation of the expression of glycosomal genes related to glycolysis and aerobic fermentation in response to heme [17,20]. Here, the aerobic fermentation of glucose overcomes mitochondrial metabolism in epimastigotes grown with heme. T. cruzi epimastigotes have enhanced glucose consumption after heme treatment, and mainly produce and secrete succinate as the final product of succinic acid fermentation. High succinate levels decreased the extracellular pH, leading to an acidification of the supernatant. However, this acidification and the great proliferation induced by heme was impaired when glycolysis was inhibited by 2-deoxy-glucose (2-DG) (gray lines). This indicates that succinate and other fermentation-related molecules are products of glycolysis, and this metabolic pathway is essential for the increment of parasite growth. In heme-cultured parasite an increase in glucose intake does not result in increased mitochondrial respiration. Mitochondrial O2 consumption related to electron transport system (ETS) is immediately reduced after glucose addition to present a Crabtree-like effect allowing organisms to maintain its energy metabolism towards aerobic glucose fermentation.