The limitations of paradigms: studies on the intermediary metabolism of Trypanosoma cruzi.

We review the development of our knowledge and interpretations of the intermediary metabolism of Trypanosoma (Schizotrypanum) cruzi. Already in the 1950's it was clearly established that when this organism was exposed to large external concentrations of carbohydrates it was unable to catabolize them completely, even in the presence of oxygen, producing a mixture of CO2, dicarboxylic acids (succinic, malic) and alanine as end products. However, subsequent work tended to emphasize such paradigmatic features as a full complement of glycolytic enzymes in all stages of the life cycle of the parasite, a functional Kreb's cycle, a cytochrome-dependent electron transport chain and phosphorylative oxidation which suggested that T. cruzi had the basic metabolic properties of classical glucose-utilizing cells, in contrast with the degenerate glycolytic metabolism of bloodstream African trypanosomes. Only in the 1980's interest revived on the how and why of the incomplete carbohydrate catabolism by this parasite. The primary reason for this anomaly was found to be the presence of a constitutive phospho-enol-pyruvate carboxykinase (PEPCK, ATP-dependent, E.C.4.1.1.49), present in all stages of the parasite's life cycle, and the lack of regulation of the glycolytic route at its classical control points, hexokinase and phosphofructokinase. On the other hand, the presence of two distinct glutamate dehydrogenases (NAD+ and NADP(+)-dependent), the former being strictly regulated by the energy charge of the cell and the Krebs' cycle activity, indicated that amino acids can be a primary source of energy for this organism.(ABSTRACT TRUNCATED AT 250 WORDS)