Aerobic fermentation of glucose by trypanosomatids

Abstract

The consumption of glucose by trypanosomatid protozoa such as Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., and Crithidia spp. is characterized by the excretion of reduced products such as succinate, pyruvate, ethanol, L-alanine, or lactate (depending on the species) not only in anaerobiosis, but also under aerobic conditions. The "aerobic fermentation" of glucose is accompanied by a complete lack, or even a reversal, of the Pasteur effect. This peculiar catabolism is mediated by a so-far unique compartmentation of the glycolytic enzymes, most of which are placed in an organelle called the glycosome; by an almost complete lack of inhibitory controls at the level of hexokinase and phosphofructokinase; and by a central role of CO2 fixation through the reaction catalyzed by phosphoenolpyruvate carboxykinase. The production of fermentative products seems to be due to a relative inefficiency of the respiratory chain, which lacks NADH dehydrogenase and the first phosphorylation site and preferentially uses succinate as substrate.

Proton nuclear magnetic resonance analysis of metabolic end products of the Bolivia strain of Trypanosoma cruzi and three of its clones

“…L-alanine, one of the main metabolites detected in our experiment and also frequently found in strains Y and Maracay, was not, however, detected in the Tuhauen strain [5]. The third main metabolite produced by our strain was glycerol, which has not been previously detected in any T. cruzi strain.…”

“…The production of acetate appears to be common to all the different strains studied: Tulahuen [4,5], Y [9], Maracay [10], and now Bolivia. L-alanine, one of the main metabolites detected in our experiment and also frequently found in strains Y and Maracay, was not, however, detected in the Tuhauen strain [5].…”

“…has a notable capacity to use carbohydrates or amino acids as carbon and energy sources [2,5]. It is also known that these species are incapable of completely degrading carbohydrates even in the presence of oxygen, producing a mixture of CO 2 , dicarboxylic acids, and alanine [5,9,10]. The relative proportion of these end products varies between different subspecies of T. cruzi [15].…”

“…Succinate can apparently be generated from glycolytic phosphoenolpyruvate, which is carboxylated to oxalacetate, and can be reduced to succinate [15]. Pyruvate is another metabolite produced by the strains Tulahuen [4,5] and Maracay [10], but was not detected in Bolivia.…”

Metabolic Changes in Glucose Transporter-deficient Leishmania mexicana and Parasite Virulence

“…Both life cycle stages of Leishmania mexicana can be cultivated in vitro (2) facilitating biochemical and genetic studies. Uptake and metabolism of glucose in Leishmania species has been of considerable interest, as this sugar provides a major source of carbon and energy to these parasites (3). In L. mexicana, glucose catabolism is 10 -20-fold higher in the promastigotes compared with amastigotes (4).…”