Article ID Journal Published Year Pages File Type
2048074 FEBS Letters 2013 7 Pages PDF
Abstract

By applying metabolic control analysis and inhibitor titration we determined the degree of control (flux control coefficient) of pyruvate:ferredoxin oxidoreductase (PFOR) and bifunctional aldehyde–alcohol dehydrogenase (ADHE) over the fluxes of fermentative glycolysis of Entamoeba histolytica subjected to aerobic conditions. The flux-control coefficients towards ethanol and acetate formation determined for PFOR titrated with diphenyleneiodonium were 0.07 and 0.09, whereas for ADHE titrated with disulfiram were 0.33 and −0.19, respectively. ADHE inhibition induced significant accumulation of glycolytic intermediates and lower ATP content. These results indicate that ADHE exerts significant flux-control on the carbon end-product formation of amoebas subjected to aerobic conditions.

► Control of the glycolytic flux was analyzed in Entamoeba histolytica under aerobic conditions. ► ADHE and PFOR control on ethanol and acetate formation was determined by inhibitor titration. ► ADHE exerted higher flux control than PFOR over fermentative glycolysis under aerobic conditions. ► Disulfiram ADHE inhibition promoted accumulation of glycolytic intermediates and low ATP content. ► ADHE (and disulfiram) showed potential to become an alternative therapeutic target (and drug).

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