Molecular and Cellular Pharmacology, Vol 4, No 3 (2012)

The Enzyme NADH-fumarate Reductase in Trypanosomatids: a Potential Target against Parasitic Diseases

Abstract

A comparison of metabolic pathways between parasites and their mammalian host points out major differences that could be exploited to develop a rational chemotherapy against the diseases caused by these parasites. One of these differences is NADH-fumarate reductase, an enzyme found in helminths, trypanosomatids and some bacteria but not in normal mammalian cells. The enzyme reverts one of the reactions in the citric acid cycle. In trypanosomatids this enzyme is localized in both the glycosome and in the single mitochondrion and is required to maintain a redox balance by producing succinate which can be used in respiration or is excreted in the extracellular space. Many drugs that inhibit this enzyme are lethal to trypanosomatids, suggesting that NADH-fumarate reductase constitutes an excellent target for the treatment of trypanosomiases and leishmaniases. In this review we summarize several studies aimed at characterizing the role of this enzyme in intermediate metabolism in trypanosomatids.

Keywords: NADH-fumarate reductase; Trypanosomatids; Glycosome; Redox balance; Antiparasitic drug targets; Trypanosomiases; Leishmaniases.

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